Free
Education  |   November 2015
Cardiac Output and Cerebral Blood Flow: The Integrated Regulation of Brain Perfusion in Adult Humans
Author Notes
  • From the Department of Anesthesia and Perioperative Care, University of California San Francisco, San Francisco, California (L.M., A.W.G.); Department of Anesthesiology, The Fourth Military Medical University Xijing Hospital, Xi’an, Shaanxi Province, China (W.H.); Department of Anesthesia and Perioperative Medicine, University of Western Ontario, London, Ontario, Canada (J.C.); and Department of Anesthesiology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China (R.H.).
  • This article is featured in “This Month in Anesthesiology,” page 1A. Figures 1–3 were enhanced by Annemarie B. Johnson, C.M.I., Medical Illustrator, Vivo Visuals, Winston-Salem, North Carolina.
    This article is featured in “This Month in Anesthesiology,” page 1A. Figures 1–3 were enhanced by Annemarie B. Johnson, C.M.I., Medical Illustrator, Vivo Visuals, Winston-Salem, North Carolina.×
  • Submitted for publication March 25, 2015. Accepted for publication July 27, 2015.
    Submitted for publication March 25, 2015. Accepted for publication July 27, 2015.×
  • Address correspondence to Dr. Gelb: Department of Anesthesia and Perioperative Care, University of California San Francisco, 521 Parnassus Avenue, Suite C450, San Francisco, California 94143. adrian.gelb@ucsf.edu. Information on purchasing reprints may be found at www.anesthesiology.org or on the masthead page at the beginning of this issue. Anesthesiology’s articles are made freely accessible to all readers, for personal use only, 6 months from the cover date of the issue.
Article Information
Education / Review Article / Cardiovascular Anesthesia / Central and Peripheral Nervous Systems / Neurosurgical Anesthesia
Education   |   November 2015
Cardiac Output and Cerebral Blood Flow: The Integrated Regulation of Brain Perfusion in Adult Humans
Anesthesiology 11 2015, Vol.123, 1198-1208. doi:10.1097/ALN.0000000000000872
Anesthesiology 11 2015, Vol.123, 1198-1208. doi:10.1097/ALN.0000000000000872
Abstract

Cerebral blood flow (CBF) is rigorously regulated by various powerful mechanisms to safeguard the match between cerebral metabolic demand and supply. The question of how a change in cardiac output (CO) affects CBF is fundamental, because CBF is dependent on constantly receiving a significant proportion of CO. The authors reviewed the studies that investigated the association between CO and CBF in healthy volunteers and patients with chronic heart failure. The overall evidence shows that an alteration in CO, either acutely or chronically, leads to a change in CBF that is independent of other CBF-regulating parameters including blood pressure and carbon dioxide. However, studies on the association between CO and CBF in patients with varying neurologic, medical, and surgical conditions were confounded by methodologic limitations. Given that CBF regulation is multifactorial but the various processes must exert their effects on the cerebral circulation simultaneously, the authors propose a conceptual framework that integrates the various CBF-regulating processes at the level of cerebral arteries/arterioles while still maintaining autoregulation. The clinical implications pertinent to the effect of CO on CBF are discussed. Outcome research relating to the management of CO and CBF in high-risk patients or during high-risk surgeries is needed.

Abstract

Cardiac output causally affects cerebral blood flow. A conceptualization is proposed for the purpose of integrating at the level of cerebral resistance vessel various mechanisms that regulate the cerebral circulation and jointly determine the brain perfusion.

THE brain, as a vital organ, disproportionately receives about 12% of cardiac output (CO) even though it weighs only 2% of the body weight.1  Cerebral blood flow (CBF) is regulated by a set of powerful mechanisms that include cerebral autoregulation,2  neurovascular coupling,3  and cerebrovascular carbon dioxide and oxygen reactivity.4  It is common to presume that a stable blood pressure or a fluctuating blood pressure as long as it is within the autoregulatory range will not lead to a noticeable change in CBF according to cerebral autoregulation. However, evidence shows that, even though the blood pressure remains stable or within the autoregulatory range, an alteration in CO, either acutely5–9  or chronically,10–19  leads to a change in CBF. Thus, it is pertinent to understand the effect of CO on CBF within the framework of cerebral autoregulation, a mechanism describing the effect of cerebral perfusion pressure on CBF.
Optimal organ perfusion is fundamental to avoiding tissue ischemia and overperfusion. There are two common theories to explain the relationship between organ perfusion and systemic hemodynamics. The first is based on an analogy to Ohm’s law: organ perfusion depends on arterial blood pressure and vascular resistance of the organ. The other is based on the distribution of CO: the blood flow of each organ is a portion of CO that is determined by the value of CO and the percentage of share based on the organ’s metabolic need.1 
The effect of CO on CBF is a topic that has not been reviewed specifically. However, it is a clinically relevant issue because both acute and chronic changes in CO are frequently encountered in clinical care. In addition, it seems that a revision of the traditional framework of cerebral autoregulation is needed to integrate the effects of cerebral perfusion pressure and CO on brain perfusion in one concordant context. This is an important consideration because blood pressure and CO are related but different systemic hemodynamic parameters, and they usually change simultaneously and may exert distinctive effects on brain perfusion.20 
The aims of this review are (1) to examine the evidence of the association between CO and CBF under varying conditions in adult humans, (2) to present a revised conceptual framework that integrates different regulatory mechanisms of brain perfusion, and (3) to discuss the relevant clinical implications.
Effect of Acute Change in CO on CBF
Evidence
A distinct association between CO and CBF was demonstrated in young healthy volunteers whose central blood volume was decreased via lower body negative pressure5,7–9  or standing up6  and increased via leg tensing,6  albumin infusion,8  or normal saline infusion9  (table 1). Each percentage change in CO corresponded to a 0.35% change in CBF, that is, there is about a 10% CBF decrease for a 30% CO reduction based on eight data pairs from five previous studies (R2 = 0.9, fig. 1). This association was unlikely to have been confounded by a change in either blood pressure or carbon dioxide because both parameters remained relatively stable except two studies in which carbon dioxide had a clinically significant drop after standing up6  and lower body negative pressure,7  respectively. It was also unlikely to be ascribed to a change in cerebral metabolic activity, because these studies were done in resting and unanesthetized subjects. Therefore, the association between CO and CBF is a causal relationship. The finding that β1-adrenergic blockade concurrently attenuated the increase in both CO and CBF induced by cycling corroborates this proposition.21 
Table 1.
Studies Investigating Simultaneous Changes in Cardiac Output and Cerebral Blood Flow via Central Blood Volume Alteration in Unanesthetized Healthy Volunteers
Studies Investigating Simultaneous Changes in Cardiac Output and Cerebral Blood Flow via Central Blood Volume Alteration in Unanesthetized Healthy Volunteers×
Studies Investigating Simultaneous Changes in Cardiac Output and Cerebral Blood Flow via Central Blood Volume Alteration in Unanesthetized Healthy Volunteers
Table 1.
Studies Investigating Simultaneous Changes in Cardiac Output and Cerebral Blood Flow via Central Blood Volume Alteration in Unanesthetized Healthy Volunteers
Studies Investigating Simultaneous Changes in Cardiac Output and Cerebral Blood Flow via Central Blood Volume Alteration in Unanesthetized Healthy Volunteers×
×
Fig. 1.
Correlation between changes in cardiac output (CO) and cerebral blood flow (CBF) in unanesthetized healthy volunteers during central blood volume alterations.5–9  All data are reported in table 1. The diameter of the dot represents the sample size that is also indicated by the number inside of each dot.
Correlation between changes in cardiac output (CO) and cerebral blood flow (CBF) in unanesthetized healthy volunteers during central blood volume alterations.5–9 All data are reported in table 1. The diameter of the dot represents the sample size that is also indicated by the number inside of each dot.
Fig. 1.
Correlation between changes in cardiac output (CO) and cerebral blood flow (CBF) in unanesthetized healthy volunteers during central blood volume alterations.5–9  All data are reported in table 1. The diameter of the dot represents the sample size that is also indicated by the number inside of each dot.
×
However, differences among the methodologies used to alter CO and measure CO and CBF should be considered during data interpretation. In these studies, the CO was altered via an acute change in central blood volume using different maneuvers, and the CO was measured using different methods even though the CBF was always assessed using transcranial Doppler (TCD; table 1). There is a chance that methodologic heterogeneity could cause inconsistent results. In addition, the practice of using TCD-measured middle cerebral artery blood flow velocity as a CBF surrogate has been cautioned against, especially in patients with cerebrovascular diseases.22,23 
In contrast, a recent study failed to define an association between cardiac index and CBF with both parameters measured using magnetic resonance imaging techniques in 31 healthy subjects of 50 to 75 yr.24  There are a multitude of differences between this study and the previous studies summarized in table 1. The most prominent is that the CO (and CBF as a consequence) was not acutely altered compared with that of the previous studies. It is worth noting that the fractional CBF, defined as the ratio of CBF to CO, was inversely correlated with cardiac index (R2 = 0.22, P = 0.008), implying that when the CO is decreased, the brain shares an increasing percentage of CO.24 
Mechanism
When the CBF was changed during acute central blood volume alteration, there must be a change in cerebrovascular resistance to account for the flow change because the blood pressure remained relatively stable. Indeed, three of four studies showed an increase in cerebrovascular resistance assessed using TCD pulsatility ratio during lower body negative pressure,5,7,8  and two studies showed a decrease during albumin or normal saline infusion.8,9  The common causes of a change in cerebrovascular resistance are (1) a change in cerebral perfusion pressure via autoregulation,2  (2) a change in cerebral metabolic activity via neurovascular coupling,3  (3) a change in arterial blood carbon dioxide partial pressure via ventilation change,25  and (4) a change in sympathetic nervous activity via the sympathetic innervation of the cerebral resistance vessels.26  The first three options are essentially excluded based on the study conditions.5,7–9  Therefore, by exclusion, this attributes the increase in cerebrovascular resistance to the sympathoexcitation incurred by central blood volume alteration.8 
During acute central blood volume alteration, the extent of the CBF change is much smaller (about one third) than the change in peripheral regional blood flow.5,8  This may be because of either the relatively minor role the sympathetic nervous system plays in the brain perfusion compared with the periphery26–29  or the countering effects by other robust CBF-regulating mechanisms that the periphery lacks. Physiologically, the differential extent of vasoconstriction in different vascular beds shunts the flow from the periphery to the brain because brain perfusion is a priority during acute CO reduction.
However, direct evidence of how the simultaneous acute changes in CO and CBF are mediated by the sympathetic nervous system is lacking, and therefore, the mechanism(s) responsible for the acute change in CBF because of an acute change in CO remains largely speculative.
Effect of Chronically Reduced CO on CBF
Evidence
Extensive evidence shows that CBF is reduced in patients diagnosed with chronic heart failure compared with that of control who do not have cardiac insufficiency (table 2).10–19  The extent of the CBF reduction correlates with the severity of the chronic heart failure assessed using New York Heart Association functional classification14  and left ventricular ejection fraction.18  The CBF reduction is reversed by interventions including cardiac transplantation,13–15  cardiac resynchronization therapy,17,19  cardioversion,30  and captopril treatment10–12  (fig. 2). Overall, a causal relationship between CO and CBF in patients with chronic heart failure is implied. This proposition is corroborated by a recent study that showed an exaggerated cerebral hypoperfusion in the upright posture in patients with heart failure compared with age- and sex-matched healthy controls.31 
Table 2.
Cerebral Blood Flow at Baseline and/or after Various Interventions in Patients with Chronic Heart Failure
Cerebral Blood Flow at Baseline and/or after Various Interventions in Patients with Chronic Heart Failure×
Cerebral Blood Flow at Baseline and/or after Various Interventions in Patients with Chronic Heart Failure
Table 2.
Cerebral Blood Flow at Baseline and/or after Various Interventions in Patients with Chronic Heart Failure
Cerebral Blood Flow at Baseline and/or after Various Interventions in Patients with Chronic Heart Failure×
×
Fig. 2.
Cerebral blood flow in patients diagnosed with chronic heart failure (CHF) before (preintervention) and after (postintervention) various interventions.10–14  The control was from patients without cardiac insufficiency. All data are reported in table 2. Only the studies that reported the control, preintervention, and postintervention values of cerebral blood flow in the units of ml min−1 100 g−1 were included. The dots with the same color are from the same study. The diameter of the dot represents the sample size that is also indicated by the number inside of each dot.
Cerebral blood flow in patients diagnosed with chronic heart failure (CHF) before (preintervention) and after (postintervention) various interventions.10–14 The control was from patients without cardiac insufficiency. All data are reported in table 2. Only the studies that reported the control, preintervention, and postintervention values of cerebral blood flow in the units of ml min−1 100 g−1 were included. The dots with the same color are from the same study. The diameter of the dot represents the sample size that is also indicated by the number inside of each dot.
Fig. 2.
Cerebral blood flow in patients diagnosed with chronic heart failure (CHF) before (preintervention) and after (postintervention) various interventions.10–14  The control was from patients without cardiac insufficiency. All data are reported in table 2. Only the studies that reported the control, preintervention, and postintervention values of cerebral blood flow in the units of ml min−1 100 g−1 were included. The dots with the same color are from the same study. The diameter of the dot represents the sample size that is also indicated by the number inside of each dot.
×
However, the methodologic heterogeneity and limitations of these studies should be recognized. The sample size in the intervention studies, especially those with cardiac transplantation, was small.13–15  The increased blood pressure after cardiac transplantation can confound the interpretation of the effect of improved CO on CBF.13,15  In rodents, captopril treatment can further reduce the lower limit of cerebral autoregulation after nephrectomy,32  decrease infarction size via CBF improvement after ischemic stroke,33  and restore cerebral autoregulation after hemorrhagic stroke.34  Therefore, studies with captopril treatment can be confounded by the direct effect of captopril on CBF regulation.10–12 
Mechanism
The mechanism underlying the CBF reduction in patients with chronic heart failure is unclear but likely related to the neurohormonal activation incurred by a failing heart. The hyperactivity of both the sympathetic nervous system and the renin–angiotensin–aldosterone axis provokes vasoconstriction of not only the peripheral vascular beds but also the cerebral vascular bed.35–38  The circulating and locally formed angiotensin II may contribute to the decrease of CBF via the AT1 receptors expressed in cerebrovascular endothelial cells and in the brain regions controlling cerebral circulation.39  Similar to the effect of acute CO reduction on CBF, the differential extent of vasoconstriction of different vascular beds shunts the flow from the periphery to the brain in patients with chronic heart failure, resulting in a lesser extent of CBF reduction than both the CO and the peripheral blood flow.35 
Neurocognitive Impairment
A relevant question that deserves discussion is what the consequences of the reduced cerebral perfusion are in patients with chronic heart failure. It is counterintuitive to assume that long-term suboptimal brain perfusion is inconsequential. Indeed, abundant evidence shows that the prevalence of cognitive dysfunction is inappropriately high in patients diagnosed with chronic heart failure.40–45  The odds ratio for cognitive impairment in patients with chronic heart failure is 1.62 with the 95% CI of 1.48 to 1.79 (P < 0.0001) based on a systematic review.43  The extent of cognitive impairment parallels the severity of chronic heart failure.42,44,46  Both cardiac resynchronization therapy47,48  and transplantation49,50  improved the impaired cognition.
Chronic heart failure is also linked to abnormal brain aging and Alzheimer disease.51–54  The relentless cerebral hypoperfusion and neurohormonal hyperactivity likely contribute to the dysfunction of the neurovascular unit.53,54  The neuronal energy crisis facilitates protein synthesis abnormalities that include impaired clearance of amyloid β and hyperphosphorylation of τ protein, ending up with the formation of amyloid-β plaques and neurofibrillary tangles.54,55 
Despite the plausible notion that there is a link among chronic heart failure, cerebral hypoperfusion, and neurocognitive dysfunction, caution is needed before claiming a causal relationship because these chronic conditions share risk factors. In addition, not every patient with neurocognitive impairment has chronic heart failure and vice versa.
Disease States Demonstrating CO–CBF Association
Vasospasm
The goal in treating vasospasm induced by subarachnoid hemorrhage is to restore the reduced CBF. One of the strategies is to augment the CO with the hope of improving the cerebral perfusion. A clinical study found that a 46% increase in CO via dobutamine infusion led to a significant increase in CBF (from 25 to 35 ml min−1 100 g−1) in the brain regions perfused by the vasospastic arteries.56  The increase in cerebral perfusion took place despite a decrease in mean arterial pressure from 113 to 108 mmHg. The result of this study was corroborated in a separate study that showed the clinical reversal of the ischemic symptoms by dobutamine infusion combined with hypervolemic preloading in 78% of symptomatic patients.57  Intraaortic balloon pump counterpulsation has also been tested in this patient population. In a report of 15 cases in which this treatment was used in patients who also had neurogenic stress cardiomyopathy, it was concluded that the use of intraaortic balloon pump counterpulsation was effective in preventing the delayed ischemic neurologic deficits.58 
Ischemic Stroke
In patients with acute ischemic stroke in the middle cerebral artery territory, an association between CO and TCD-estimated CBF was demonstrated in the affected, but not the unaffected, brain region when using hypervolemic hemodilution combined with dopamine–dobutamine infusions.59  Intraaortic balloon pump counterpulsation was also found to increase TCD-estimated CBF by 21 and 11% in patients with acute ischemic stroke whose left ventricular ejection fractions were 28 and 44%, respectively.60  Intraaortic balloon pump counterpulsation normally decreases systolic blood pressure, increases diastolic blood pressure, and produces little or no change in mean blood pressure in normotensive patients.61  Therefore, it is reasonable to attribute the improvement of the CBF to the augmentation of the CO during the application of intraaortic balloon pump counterpulsation.
Sepsis
In studies conducted in septic patients, dobutamine infusion increased both cardiac index (from 3.4 to 4.2 l min−1 m−2 and from 3.8 to 6.3 l min−1 m−2) and TCD-estimated CBF (from 52 to 62 cm/s and from 68 to 80 cm/s), whereas the increase in mean arterial pressure was from 85 to 91 mmHg and from 77 to 86 mmHg, respectively.62,63  Both studies showed a better correlation between CO and CBF than between blood pressure and CBF using both the relative changes of parameters63  and the absolute values of measurements.62 
Disease States Demonstrating a Lack of CO–CBF Association
Head Injury
An association between changes in CO and CBF (133Xe washout) was not found during treatment with phenylephrine, trimethaphan or mannitol in comatose and ventilated patients with severe head injury.64  Phenylephrine, which is a peripheral vasoconstrictor used to increase blood pressure, actually causes a decrease in CO.20  This may have confounded the study. An increase in perfusion pressure can lead to an increase in CBF in neurologically critically ill patients who have impaired autoregulation65 ; as a result, phenylephrine treatment likely causes opposite changes in CBF (increase) and CO (decrease).
Neurologic Surgery
CBF is normally increased after surgical resection of brain arteriovenous malformations. However, an association between changes in CO and CBF (133Xe washout) based on the preresection and postresection measurements was not found in this patient population.66  Hemodynamic variables including CO, arterial blood pressure, central venous pressure, and pulmonary artery diastolic pressure remained stable in the face of the increase in CBF. Brain arteriovenous malformations have unique hemodynamic physiology including the relatively low transnidal pressure gradient that may shunt a portion of CBF through the lesion.67  Thus, it is speculated that after surgical resection, the portion of CBF originally going through the arteriovenous malformation reroutes through the normal brain resulting in a regionally increased CBF in the face of unchanged systemic hemodynamics.
Cardiac Surgery
Cardiac surgery with cardiopulmonary bypass is a special situation in which organ perfusion is propelled by an extracorporeal centrifugal pump. How the pump flow affects the cerebral perfusion depends on the blood gas management.68  With α-stat management, CBF (133Xe washout) is correlated with blood pressure, not pump flow.69  With pH-stat management, CBF (argon saturation and desaturation method) is correlated with pump flow in the face of a stable blood pressure.70  The precise mechanism(s) underlying this discrepancy is unclear. The cerebral vasodilation induced by hypercapnia may be responsible, because carbon dioxide is often added during pH-stat management but not during α-stat management.71  Hypothermic cardiopulmonary bypass suppresses sympathetic nervous activity72  and that may also alter the association between CO and CBF.
Hepatic Failure
An association between CO and CBF (133Xe washout) was not found in patients with fulminant hepatic failure.73  However, this study was underpowered with only eight pairs of data, and the statistical insignificance likely reflects a single outlier. This study also found that the norepinephrine-induced changes in CO and TCD-estimated CBF did not correlate with each other. However, norepinephrine primarily increases blood pressure and has unpredictable effects on CO.74  Therefore, the study was confounded by the simultaneous change in blood pressure.
Cardiology
A study performed in patients with coronary heart disease or cardiomyopathy referred for echocardiography failed to show an association between CO and CBF.75  However, the study was confounded by the use of common carotid artery blood flow measured using color M-mode duplex system as a surrogate for CBF as the external carotid artery blood flow is included.
Integrated Regulation of CBF
CBF is rigorously regulated by multiple powerful mechanisms to safeguard the matching of cerebral metabolic demand and supply.76  CO is one of the physiologic processes that contribute to CBF regulation. However, exactly how an alteration in CO, in the face of a stable blood pressure, leads to a change in CBF is not entirely clear. A proposal that integrates various CBF-regulating mechanisms, including the role of blood pressure and CO, in one concordant conceptualization seems necessary.
A conceptual framework of the integrated regulation of the brain perfusion is proposed (fig. 3). It needs to be appreciated that the various mechanisms, no matter how distinctive, all exert their regulatory effects on the same target, that is, the cerebral resistance vessels. Different mechanisms may affect different segments of the cerebral resistance vessels. For example, sympathetic stimulation constricts large cerebral arteries, whereas an increase in blood pressure constricts the arterioles.77  The various CBF-regulating mechanisms integrate at the level of the cerebral resistance vessels and generate only one consequence that is the extent of the cerebrovascular resistance. Therefore, how CBF is changed after a change in any of the regulatory processes depends on how the different mechanisms are integrated. Different mechanisms likely have different degrees of regulatory power likely determined by the physiologic priority in the context of the clinical situation. The one with the major regulatory power plays a dominant role, whereas one with minor power plays a smaller role.
Fig. 3.
The conceptual framework of the integrated regulation of brain perfusion. The cerebrovascular resistance determined by the caliber of the cerebral resistance vessels is regulated by various physiologic processes: (1) cardiac output (CO) likely via sympathetic nervous activity (SNA) and renin–angiotensin–aldosterone (RAA) system, depending on the chronicity of the change in CO,5–19  (2) arterial blood pressure (ABP) and cerebral perfusion pressure (CPP) via cerebral autoregulation,2,71  (3) cerebral metabolic activity via neurovascular coupling,3,76  and (4) arterial blood carbon dioxide (CO2)4,25,71  and oxygen (O2)4  via cerebrovascular reactivity. The SNA regulates cerebral blood flow26–29  and may play a prominent role during acute hypertension and hypercapnia29  as a protective mechanism preventing cerebral overperfusion (dashed line). These various regulatory mechanisms, together with other CBF-regulatory mechanisms that are not specified here such as anesthetic effects, integrate at the level of the cerebral resistance vessels and generate only one consequence, which is the extent of the cerebrovascular resistance and, therefore, jointly regulate brain perfusion. The plateau of the autoregulation curve shifts downward when the CO is reduced and upward when augmented. The position of the plateau is determined by the caliber (R) of the cerebral resistance vessels at high (Rhigh), normal (Rnorm), and low (Rlow) CO. The scale of CO on the right side is smaller than that of CBF on the left side to reflect the lesser extent of change in CBF induced by an alteration of CO.
The conceptual framework of the integrated regulation of brain perfusion. The cerebrovascular resistance determined by the caliber of the cerebral resistance vessels is regulated by various physiologic processes: (1) cardiac output (CO) likely via sympathetic nervous activity (SNA) and renin–angiotensin–aldosterone (RAA) system, depending on the chronicity of the change in CO,5–19 (2) arterial blood pressure (ABP) and cerebral perfusion pressure (CPP) via cerebral autoregulation,2,71 (3) cerebral metabolic activity via neurovascular coupling,3,76 and (4) arterial blood carbon dioxide (CO2)4,25,71 and oxygen (O2)4 via cerebrovascular reactivity. The SNA regulates cerebral blood flow26–29 and may play a prominent role during acute hypertension and hypercapnia29 as a protective mechanism preventing cerebral overperfusion (dashed line). These various regulatory mechanisms, together with other CBF-regulatory mechanisms that are not specified here such as anesthetic effects, integrate at the level of the cerebral resistance vessels and generate only one consequence, which is the extent of the cerebrovascular resistance and, therefore, jointly regulate brain perfusion. The plateau of the autoregulation curve shifts downward when the CO is reduced and upward when augmented. The position of the plateau is determined by the caliber (R) of the cerebral resistance vessels at high (Rhigh), normal (Rnorm), and low (Rlow) CO. The scale of CO on the right side is smaller than that of CBF on the left side to reflect the lesser extent of change in CBF induced by an alteration of CO.
Fig. 3.
The conceptual framework of the integrated regulation of brain perfusion. The cerebrovascular resistance determined by the caliber of the cerebral resistance vessels is regulated by various physiologic processes: (1) cardiac output (CO) likely via sympathetic nervous activity (SNA) and renin–angiotensin–aldosterone (RAA) system, depending on the chronicity of the change in CO,5–19  (2) arterial blood pressure (ABP) and cerebral perfusion pressure (CPP) via cerebral autoregulation,2,71  (3) cerebral metabolic activity via neurovascular coupling,3,76  and (4) arterial blood carbon dioxide (CO2)4,25,71  and oxygen (O2)4  via cerebrovascular reactivity. The SNA regulates cerebral blood flow26–29  and may play a prominent role during acute hypertension and hypercapnia29  as a protective mechanism preventing cerebral overperfusion (dashed line). These various regulatory mechanisms, together with other CBF-regulatory mechanisms that are not specified here such as anesthetic effects, integrate at the level of the cerebral resistance vessels and generate only one consequence, which is the extent of the cerebrovascular resistance and, therefore, jointly regulate brain perfusion. The plateau of the autoregulation curve shifts downward when the CO is reduced and upward when augmented. The position of the plateau is determined by the caliber (R) of the cerebral resistance vessels at high (Rhigh), normal (Rnorm), and low (Rlow) CO. The scale of CO on the right side is smaller than that of CBF on the left side to reflect the lesser extent of change in CBF induced by an alteration of CO.
×
The effect of CO on CBF can be appreciated within the framework of cerebral autoregulation (fig. 3). When CO is decreased, the plateau descends slightly reflecting the smaller decrease in CBF, and vice versa; however, the overall autoregulatory mechanism is maintained. This proposition is corroborated by the finding that dynamic cerebral autoregulation is not affected by the acute change in CO.78  Thus, this speculative proposal integrates the effects of blood pressure and CO on brain perfusion. However, how the lower and upper limits of the autoregulation curve are changed and whether the plateau tilts when the CO is altered are unknown.
The lesser extent to which CBF changes compared with that of CO or peripheral blood flow during acute or chronic CO alterations can be explained by the fact that the extent to which CBF is changed is determined by the integrated effect of all CBF-regulating mechanisms. Other powerful CBF-regulating mechanisms unrelated to CO may buffer the effect of CO on CBF, causing a lesser flow change in the brain compared with the organs that are not influenced by these mechanisms.
Clinical Implications
Acute changes in CO because of a variety of etiologies such as dehydration, blood loss, body tilt, mechanical ventilation, intraabdominal insufflation, pneumothorax, hemothorax, diuresis, vasodilation, sympatholysis, anesthetic agent, pulmonary embolization, myocardial infarction, and arrhythmia are frequently encountered in the operating room. CBF may decrease when the CO is reduced. Therefore, for the purpose of maintaining CBF, any adverse change in CO should be remedied. Goal-directed fluid therapy for the purpose of CO optimization has been shown to be associated with an improved overall outcome after intraabdominal surgeries.79,80  However, to what degree this favorable outcome is attributable to the optimization of CBF is unknown.
It seems reasonable to advocate intraoperative monitoring of both CO and CBF in patients with reduced cardiac function or cerebrovascular obstructive diseases or during high-risk surgeries that have a greater chance of causing hemodynamic fluctuation. The currently unanswered question is how best to monitor both parameters continuously and noninvasively and which patient populations benefit the most from this strategy of care.
In the perioperative setting, it needs to be emphasized that the cerebral circulation is affected by multiple processes, and CO is one of them. Anesthesia itself affects cerebral perfusion via a variety of pathways that include the suppression of cerebral metabolic activity,81  intrinsic cerebral vasodilation by volatile agents,82  impairment of cerebral autoregulation by volatile agents,83  suppression of the sympathetic nervous activity,84  and disturbance of the systemic hemodynamics.85  Therefore, the association between CO and CBF learned from studies performed in unanesthetized healthy volunteers may not always apply in the anesthetized surgical patients.
Chronic heart failure is prevalent affecting approximately 2% of the adult population and is associated with a high mortality.86  Its prevalence increases sharply with age, affecting 10% of the population aged 65 yr or older.87  An increasing number of patients diagnosed with chronic heart failure are expected to present to the operating room for surgery, and this poses a great challenge for perioperative care. It is judicious to avoid acute reductions of both CO and CBF on top of the chronic cardiac insufficiency and cerebral hypoperfusion. This mandates thoughtful preoperative preparation, adept appreciation of cardiovascular and cerebrovascular physiology and their interaction, and preemptively preventing circumstances that threaten cardiac performance and brain perfusion.
Studies on the association between CO and CBF in patients with major neurologic, medical, or surgical conditions are confounded by methodologic limitations. However, it seems that interventions that enhance cardiac performance may improve perfusion of the ischemic brain, especially in patients with impaired cardiac function (fig. 2).56–60  It is important although to remember that drugs that increase blood pressure such as phenylephrine and norepinephrine may actually decrease CO.20,74  In contrast, dobutamine and volume augmentation can increase the CO but not necessarily blood pressure. The effect of a vasopressor on CBF likely depends on the drug being used, the disease state, and the functional status of the regulatory mechanisms of brain perfusion.88,89  Currently, long-term outcome data relevant to the choice of vasopressor in various clinical situations is lacking.
The proposed conceptualization integrating various CBF-regulating mechanisms within the framework of cerebral autoregulation has important clinical implications. The habitual thinking that how the brain is perfused is merely dependent on the blood pressure should be abandoned. The autoregulatory curve should be regarded as a dynamic process, meaning that its shape, plateau, and the lower and upper limits may change depending on the integrated effect of nonpressure but CBF-regulating mechanisms including the CO.71  For a given value of blood pressure, even though it is deemed clinically acceptable, the CBF may be either higher or lower than that estimated by the traditional autoregulatory curve. Therefore, the management of CBF should be guided by a multifactorial but integrated framework of CBF regulation, especially in patients who are at risk of cerebral ischemia.
Overall, these recommendations are largely based on physiologic studies in healthy volunteers and patients with chronic heart failure or other diagnoses. Meaningful outcome research pertinent to the management of CO and CBF is needed to better guide clinical practice. Moreover, noninvasive or minimally invasive, reliable, and continuous CO monitoring, as well as CBF monitoring or its surrogates, need to be considered for use in high-risk patients or during high-risk surgeries.
Summary
As one of the most important systemic hemodynamic parameters, CO contributes to the regulation of CBF likely via the sympathetic nervous activity, with or without the renin–angiotensin system depending on the acuteness or chronicity of change. The various mechanisms that regulate the cerebral circulation integrate at the level of the cerebral resistance vessels and jointly determine the brain perfusion. The effect of CO on brain perfusion should be integrated into the framework of cerebral autoregulation. The clinical considerations are confounded by methodologic limitations. Interventions aimed at enhancing cardiac performance and improving brain perfusion need to be tested by relevant clinical outcomes research.
Acknowledgments
This study was supported by the Inaugural Anesthesia Department Awards for Seed Funding for Clinically Oriented Research Projects from the Department of Anesthesia and Perioperative Care, University of California San Francisco, San Francisco, California (to Dr. Meng).
Competing Interests
The authors declare no competing interests.
References
Williams, LR, Leggett, RW Reference values for resting blood flow to organs of man.. Clin Phys Physiol Meas. (1989). 10 187–217 [Article] [PubMed]
Paulson, OB, Strandgaard, S, Edvinsson, L Cerebral autoregulation.. Cerebrovasc Brain Metab Rev. (1990). 2 161–92 [PubMed]
Girouard, H, Iadecola, C Neurovascular coupling in the normal brain and in hypertension, stroke, and Alzheimer disease.. J Appl Physiol. (2006). 100 328–35 [Article] [PubMed]
Kety, SS, Schmidt, CF The effects of altered arterial tensions of carbon dioxide and oxygen on cerebral blood flow and cerebral oxygen consumption of normal young men.. J Clin Invest. (1948). 27 484–92 [Article] [PubMed]
Levine, BD, Giller, CA, Lane, LD, Buckey, JC, Blomqvist, CG Cerebral versus systemic hemodynamics during graded orthostatic stress in humans.. Circulation. (1994). 90 298–306 [Article] [PubMed]
van Lieshout, JJ, Pott, F, Madsen, PL, van Goudoever, J, Secher, NH Muscle tensing during standing: Effects on cerebral tissue oxygenation and cerebral artery blood velocity.. Stroke. (2001). 32 1546–51 [Article] [PubMed]
Brown, CM, Dütsch, M, Hecht, MJ, Neundörfer, B, Hilz, MJ Assessment of cerebrovascular and cardiovascular responses to lower body negative pressure as a test of cerebral autoregulation.. J Neurol Sci. (2003). 208 71–8 [Article] [PubMed]
Ogoh, S, Brothers, RM, Barnes, Q, Eubank, WL, Hawkins, MN, Purkayastha, S, O-Yurvati, A, Raven, PB The effect of changes in cardiac output on middle cerebral artery mean blood velocity at rest and during exercise.. J Physiol. (2005). 569(Pt 2) 697–704 [Article] [PubMed]
Ogawa, Y, Iwasaki, K, Aoki, K, Shibata, S, Kato, J, Ogawa, S Central hypervolemia with hemodilution impairs dynamic cerebral autoregulation.. Anesth Analg. (2007). 105 1389–96 [Article] [PubMed]
Rajagopalan, B, Raine, AE, Cooper, R, Ledingham, JG Changes in cerebral blood flow in patients with severe congestive cardiac failure before and after captopril treatment.. Am J Med. (1984). 76 86–90 [Article] [PubMed]
Paulson, OB, Jarden, JO, Godtfredsen, J, Vorstrup, S Cerebral blood flow in patients with congestive heart failure treated with captopril.. Am J Med. (1984). 76 91–5 [Article] [PubMed]
Paulson, OB, Jarden, JO, Vorstrup, S, Holm, S, Godtfredsen, J Effect of captopril on the cerebral circulation in chronic heart failure.. Eur J Clin Invest. (1986). 16 124–32 [Article] [PubMed]
Gruhn, N, Larsen, FS, Boesgaard, S, Knudsen, GM, Mortensen, SA, Thomsen, G, Aldershvile, J Cerebral blood flow in patients with chronic heart failure before and after heart transplantation.. Stroke. (2001). 32 2530–3 [Article] [PubMed]
Choi, BR, Kim, JS, Yang, YJ, Park, KM, Lee, CW, Kim, YH, Hong, MK, Song, JK, Park, SW, Park, SJ, Kim, JJ Factors associated with decreased cerebral blood flow in congestive heart failure secondary to idiopathic dilated cardiomyopathy.. Am J Cardiol. (2006). 97 1365–9 [Article] [PubMed]
Massaro, AR, Dutra, AP, Almeida, DR, Diniz, RV, Malheiros, SM Transcranial Doppler assessment of cerebral blood flow: Effect of cardiac transplantation.. Neurology. (2006). 66 124–6 [Article] [PubMed]
Vogels, RL, Oosterman, JM, Laman, DM, Gouw, AA, Schroeder-Tanka, JM, Scheltens, P, van der Flier, WM, Weinstein, HC Transcranial Doppler blood flow assessment in patients with mild heart failure: Correlates with neuroimaging and cognitive performance.. Congest Heart Fail. (2008). 14 61–5 [Article] [PubMed]
van Bommel, RJ, Marsan, NA, Koppen, H, Delgado, V, Borleffs, CJ, Ypenburg, C, Bertini, M, Schalij, MJ, Bax, JJ Effect of cardiac resynchronization therapy on cerebral blood flow.. Am J Cardiol. (2010). 106 73–7 [Article] [PubMed]
Loncar, G, Bozic, B, Lepic, T, Dimkovic, S, Prodanovic, N, Radojicic, Z, Cvorovic, V, Markovic, N, Brajovic, M, Despotovic, N, Putnikovic, B, Popovic-Brkic, V Relationship of reduced cerebral blood flow and heart failure severity in elderly males.. Aging Male. (2011). 14 59–65 [Article] [PubMed]
Ozdemir, O, Soylu, M, Durmaz, T, Tosun, O Early haemodynamic changes in cerebral blood flow after cardiac resychronisation therapy.. Heart Lung Circ. (2013). 22 260–4 [Article] [PubMed]
Meng, L, Cannesson, M, Alexander, BS, Yu, Z, Kain, ZN, Cerussi, AE, Tromberg, BJ, Mantulin, WW Effect of phenylephrine and ephedrine bolus treatment on cerebral oxygenation in anaesthetized patients.. Br J Anaesth. (2011). 107 209–17 [Article] [PubMed]
Ide, K, Pott, F, Van Lieshout, JJ, Secher, NH Middle cerebral artery blood velocity depends on cardiac output during exercise with a large muscle mass.. Acta Physiol Scand. (1998). 162 13–20 [Article] [PubMed]
Démolis, P, Tran Dinh, YR, Giudicelli, JF Relationships between cerebral regional blood flow velocities and volumetric blood flows and their respective reactivities to acetazolamide.. Stroke. (1996). 27 1835–9 [Article] [PubMed]
Clyde, BL, Resnick, DK, Yonas, H, Smith, HA, Kaufmann, AM The relationship of blood velocity as measured by transcranial doppler ultrasonography to cerebral blood flow as determined by stable xenon computed tomographic studies after aneurysmal subarachnoid hemorrhage.. Neurosurgery. (1996). 38 896–904 [Article] [PubMed]
Henriksen, OM, Jensen, LT, Krabbe, K, Larsson, HB, Rostrup, E Relationship between cardiac function and resting cerebral blood flow: MRI measurements in healthy elderly subjects.. Clin Physiol Funct Imaging. (2014). 34 471–7 [Article] [PubMed]
Harper, AM, Glass, HI Effect of alterations in the arterial carbon dioxide tension on the blood flow through the cerebral cortex at normal and low arterial blood pressures.. J Neurol Neurosurg Psychiatry. (1965). 28 449–52 [Article] [PubMed]
Cencetti, S, Lagi, A, Cipriani, M, Fattorini, L, Bandinelli, G, Bernardi, L Autonomic control of the cerebral circulation during normal and impaired peripheral circulatory control.. Heart. (1999). 82 365–72 [Article] [PubMed]
Nelson, E, Rennels, M Innervation of intracranial arteries.. Brain. (1970). 93 475–90 [Article] [PubMed]
Edvinsson, L Innervation of the cerebral circulation.. Ann N Y Acad Sci. (1987). 519 334–48 [Article] [PubMed]
ter Laan, M, van Dijk, JM, Elting, JW, Staal, MJ, Absalom, AR Sympathetic regulation of cerebral blood flow in humans: A review.. Br J Anaesth. (2013). 111 361–7 [Article] [PubMed]
Petersen, P, Kastrup, J, Videbaek, R, Boysen, G Cerebral blood flow before and after cardioversion of atrial fibrillation.. J Cereb Blood Flow Metab. (1989). 9 422–5 [Article] [PubMed]
Fraser, KS, Heckman, GA, McKelvie, RS, Harkness, K, Middleton, LE, Hughson, RL Cerebral hypoperfusion is exaggerated with an upright posture in heart failure: Impact of depressed cardiac output.. JACC Heart Fail. (2015). 3 168–75 [Article] [PubMed]
Pedersen, TF, Paulson, OB, Nielsen, AH, Strandgaard, S Effect of nephrectomy and captopril on autoregulation of cerebral blood flow in rats.. Am J Physiol Heart Circ Physiol. (2003). 285 H1097–104 [Article] [PubMed]
Ito, T, Yamakawa, H, Bregonzio, C, Terrón, JA, Falcón-Neri, A, Saavedra, JM Protection against ischemia and improvement of cerebral blood flow in genetically hypertensive rats by chronic pretreatment with an angiotensin II AT1 antagonist.. Stroke. (2002). 33 2297–303 [Article] [PubMed]
Smeda, JS, Daneshtalab, N The effects of poststroke captopril and losartan treatment on cerebral blood flow autoregulation in SHRsp with hemorrhagic stroke.. J Cereb Blood Flow Metab. (2011). 31 476–85 [Article] [PubMed]
Zelis, R, Sinoway, LI, Musch, TI, Davis, D, Just, H Regional blood flow in congestive heart failure: Concept of compensatory mechanisms with short and long time constants.. Am J Cardiol. (1988). 62 2E–8E [Article] [PubMed]
Francis, GS The relationship of the sympathetic nervous system and the renin-angiotensin system in congestive heart failure.. Am Heart J. (1989). 118 642–8 [Article] [PubMed]
Packer, M The neurohormonal hypothesis: A theory to explain the mechanism of disease progression in heart failure.. J Am Coll Cardiol. (1992). 20 248–54 [Article] [PubMed]
Patterson, JH, Adams, KFJr Pathophysiology of heart failure: Changing perceptions.. Pharmacotherapy. (1996). 16(2 Pt 2) 27S–36S [PubMed]
Saavedra, JM, Benicky, J, Zhou, J Mechanisms of the anti-ischemic effect of angiotensin II AT(1) receptor antagonists in the brain.. Cell Mol Neurobiol. (2006). 26 1099–111 [PubMed]
Trojano, L, Antonelli Incalzi, R, Acanfora, D, Picone, C, Mecocci, P, Rengo, F Congestive Heart Failure Italian Study Investigators, Cognitive impairment: A key feature of congestive heart failure in the elderly.. J Neurol. (2003). 250 1456–63 [Article] [PubMed]
Heckman, GA, Patterson, CJ, Demers, C, St Onge, J, Turpie, ID, McKelvie, RS Heart failure and cognitive impairment: Challenges and opportunities.. Clin Interv Aging. (2007). 2 209–18 [PubMed]
Cohen, MB, Mather, PJ A review of the association between congestive heart failure and cognitive impairment.. Am J Geriatr Cardiol. (2007). 16 171–4 [Article] [PubMed]
Vogels, RL, Scheltens, P, Schroeder-Tanka, JM, Weinstein, HC Cognitive impairment in heart failure: A systematic review of the literature.. Eur J Heart Fail. (2007). 9 440–9 [Article] [PubMed]
Debette, S, Bauters, C, Leys, D, Lamblin, N, Pasquier, F, de Groote, P Prevalence and determinants of cognitive impairment in chronic heart failure patients.. Congest Heart Fail. (2007). 13 205–8 [Article] [PubMed]
Sauvé, MJ, Lewis, WR, Blankenbiller, M, Rickabaugh, B, Pressler, SJ Cognitive impairments in chronic heart failure: A case controlled study.. J Card Fail. (2009). 15 1–10 [Article] [PubMed]
Putzke, JD, Williams, MA, Rayburn, BK, Kirklin, JK, Boll, TJ The relationship between cardiac function and neuropsychological status among heart transplant candidates.. J Card Fail. (1998). 4 295–303 [Article] [PubMed]
Conti, JB, Sears, SF Cardiac resynchronization therapy: Can we make our heart failure patients smarter?. Trans Am Clin Climatol Assoc. (2007). 118 153–64 [PubMed]
Dixit, NK, Vazquez, LD, Cross, NJ, Kuhl, EA, Serber, ER, Kovacs, A, Dede, DE, Conti, JB, Sears, SF Cardiac resynchronization therapy: A pilot study examining cognitive change in patients before and after treatment.. Clin Cardiol. (2010). 33 84–8 [Article] [PubMed]
Bornstein, RA, Starling, RC, Myerowitz, PD, Haas, GJ Neuropsychological function in patients with end-stage heart failure before and after cardiac transplantation.. Acta Neurol Scand. (1995). 91 260–5 [Article] [PubMed]
Roman, DD, Kubo, SH, Ormaza, S, Francis, GS, Bank, AJ, Shumway, SJ Memory improvement following cardiac transplantation.. J Clin Exp Neuropsychol. (1997). 19 692–7 [Article] [PubMed]
Jefferson, AL, Himali, JJ, Beiser, AS, Au, R, Massaro, JM, Seshadri, S, Gona, P, Salton, CJ, DeCarli, C, O’Donnell, CJ, Benjamin, EJ, Wolf, PA, Manning, WJ Cardiac index is associated with brain aging: The Framingham Heart Study.. Circulation. (2010). 122 690–7 [Article] [PubMed]
Jefferson, AL, Himali, JJ, Au, R, Seshadri, S, Decarli, C, O’Donnell, CJ, Wolf, PA, Manning, WJ, Beiser, AS, Benjamin, EJ Relation of left ventricular ejection fraction to cognitive aging (from the Framingham Heart Study).. Am J Cardiol. (2011). 108 1346–51 [Article] [PubMed]
de la Torre, JC Cardiovascular risk factors promote brain hypoperfusion leading to cognitive decline and dementia.. Cardiovasc Psychiatry Neurol. (2012). 2012 367516 [Article] [PubMed]
Cermakova, P, Eriksdotter, M, Lund, LH, Winblad, B, Religa, P, Religa, D Heart failure and Alzheimer’s disease.. J Intern Med. (2015). 277 406–25 [Article] [PubMed]
de la Torre, JC Pathophysiology of neuronal energy crisis in Alzheimer’s disease.. Neurodegener Dis. (2008). 5 126–32 [Article] [PubMed]
Kim, DH, Joseph, M, Ziadi, S, Nates, J, Dannenbaum, M, Malkoff, M Increases in cardiac output can reverse flow deficits from vasospasm independent of blood pressure: A study using xenon computed tomographic measurement of cerebral blood flow.. Neurosurgery. (2003). 53 1044–51 [Article] [PubMed]
Levy, ML, Rabb, CH, Zelman, V, Giannotta, SL Cardiac performance enhancement from dobutamine in patients refractory to hypervolemic therapy for cerebral vasospasm.. J Neurosurg. (1993). 79 494–9 [Article] [PubMed]
Lazaridis, C, Pradilla, G, Nyquist, PA, Tamargo, RJ Intra-aortic balloon pump counterpulsation in the setting of subarachnoid hemorrhage, cerebral vasospasm, and neurogenic stress cardiomyopathy. Case report and review of the literature.. Neurocrit Care. (2010). 13 101–8 [Article] [PubMed]
Treib, J, Haass, A, Koch, D, Grauer, MT, Stoll, M, Schimrigk, K Influence of blood pressure and cardiac output on cerebral blood flow and autoregulation in acute stroke measured by TCD.. Eur J Neurol. (1996). 3 539–43 [Article]
Pfluecke, C, Christoph, M, Kolschmann, S, Tarnowski, D, Forkmann, M, Jellinghaus, S, Poitz, DM, Wunderlich, C, Strasser, RH, Schoen, S, Ibrahim, K Intra-aortic balloon pump (IABP) counterpulsation improves cerebral perfusion in patients with decreased left ventricular function.. Perfusion. (2014). 29 511–6 [Article] [PubMed]
Trost, JC, Hillis, LD Intra-aortic balloon counterpulsation.. Am J Cardiol. (2006). 97 1391–8 [Article] [PubMed]
Berré, J, De Backer, D, Moraine, JJ, Vincent, JL, Kahn, RJ Effects of dobutamine and prostacyclin on cerebral blood flow velocity in septic patients.. J Crit Care. (1994). 9 1–6 [Article] [PubMed]
Berré, J, De Backer, D, Moraine, JJ, Mélot, C, Kahn, RJ, Vincent, JL Dobutamine increases cerebral blood flow velocity and jugular bulb hemoglobin saturation in septic patients.. Crit Care Med. (1997). 25 392–8 [Article] [PubMed]
Bouma, GJ, Muizelaar, JP Relationship between cardiac output and cerebral blood flow in patients with intact and with impaired autoregulation.. J Neurosurg. (1990). 73 368–74 [Article] [PubMed]
Engelborghs, K, Haseldonckx, M, Van Reempts, J, Van Rossem, K, Wouters, L, Borgers, M, Verlooy, J Impaired autoregulation of cerebral blood flow in an experimental model of traumatic brain injury.. J Neurotrauma. (2000). 17 667–77 [Article] [PubMed]
Hashimoto, T, Young, WL, Prohovnik, I, Gupta, DK, Ostapkovich, ND, Ornstein, E, Halim, AX, Quick, CM Increased cerebral blood flow after brain arteriovenous malformation resection is substantially independent of changes in cardiac output.. J Neurosurg Anesthesiol. (2002). 14 204–8 [Article] [PubMed]
Young, WL, Kader, A, Pile-Spellman, J, Ornstein, E, Stein, BM Arteriovenous malformation draining vein physiology and determinants of transnidal pressure gradients. The Columbia University AVM Study Project.. Neurosurgery. (1994). 35 389–95 [Article] [PubMed]
Schell, RM, Kern, FH, Greeley, WJ, Schulman, SR, Frasco, PE, Croughwell, ND, Newman, M, Reves, JG Cerebral blood flow and metabolism during cardiopulmonary bypass.. Anesth Analg. (1993). 76 849–65 [Article] [PubMed]
Schwartz, AE, Sandhu, AA, Kaplon, RJ, Young, WL, Jonassen, AE, Adams, DC, Edwards, NM, Sistino, JJ, Kwiatkowski, P, Michler, RE Cerebral blood flow is determined by arterial pressure and not cardiopulmonary bypass flow rate.. Ann Thorac Surg. (1995). 60 165–9 [Article] [PubMed]
Soma, Y, Hirotani, T, Yozu, R, Onoguchi, K, Misumi, T, Kawada, K, Inoue, T A clinical study of cerebral circulation during extracorporeal circulation.. J Thorac Cardiovasc Surg. (1989). 97 187–93 [PubMed]
Meng, L, Gelb, AW Regulation of cerebral autoregulation by carbon dioxide.. Anesthesiology. (2015). 122 196–205 [Article] [PubMed]
Tokunaga, S, Imaizumi, T, Fukae, K, Nakashima, A, Hisahara, M, Tominaga, R, Takeshita, A, Yasui, H, Tokunaga, K Effects of hypothermia during cardiopulmonary bypass and circulatory arrest on sympathetic nerve activity in rabbits.. Cardiovasc Res. (1996). 31 769–76 [Article] [PubMed]
Larsen, FS, Strauss, G, Knudsen, GM, Herzog, TM, Hansen, BA, Secher, NH Cerebral perfusion, cardiac output, and arterial pressure in patients with fulminant hepatic failure.. Crit Care Med. (2000). 28 996–1000 [Article] [PubMed]
Maas, JJ, Pinsky, MR, de Wilde, RB, de Jonge, E, Jansen, JR Cardiac output response to norepinephrine in postoperative cardiac surgery patients: Interpretation with venous return and cardiac function curves.. Crit Care Med. (2013). 41 143–50 [Article] [PubMed]
Eicke, BM, von Schlichting, J, Mohr-Ahaly, S, Schlosser, A, von Bardeleben, RS, Krummenauer, F, Hopf, HC Lack of association between carotid artery volume blood flow and cardiac output.. J Ultrasound Med. (2001). 20 1293–8 [PubMed]
Bor-Seng-Shu, E, Kita, WS, Figueiredo, EG, Paiva, WS, Fonoff, ET, Teixeira, MJ, Panerai, RB Cerebral hemodynamics: Concepts of clinical importance.. Arq Neuropsiquiatr. (2012). 70 352–6 [PubMed]
Baumbach, GL, Heistad, DD Effects of sympathetic stimulation and changes in arterial pressure on segmental resistance of cerebral vessels in rabbits and cats.. Circ Res. (1983). 52 527–33 [Article] [PubMed]
Deegan, BM, Devine, ER, Geraghty, MC, Jones, E, Ólaighin, G, Serrador, JM The relationship between cardiac output and dynamic cerebral autoregulation in humans.. J Appl Physiol. (2010). 109 1424–31 [Article] [PubMed]
Gan, TJ, Soppitt, A, Maroof, M, el-Moalem, H, Robertson, KM, Moretti, E, Dwane, P, Glass, PS Goal-directed intraoperative fluid administration reduces length of hospital stay after major surgery.. Anesthesiology. (2002). 97 820–6 [Article] [PubMed]
Wakeling, HG, McFall, MR, Jenkins, CS, Woods, WG, Miles, WF, Barclay, GR, Fleming, SC Intraoperative oesophageal Doppler guided fluid management shortens postoperative hospital stay after major bowel surgery.. Br J Anaesth. (2005). 95 634–42 [Article] [PubMed]
Stullken, EHJr, Milde, JH, Michenfelder, JD, Tinker, JH The nonlinear responses of cerebral metabolism to low concentrations of halothane, enflurane, isoflurane, and thiopental.. Anesthesiology. (1977). 46 28–34 [Article] [PubMed]
Matta, BF, Mayberg, TS, Lam, AM Direct cerebrovasodilatory effects of halothane, isoflurane, and desflurane during propofol-induced isoelectric electroencephalogram in humans.. Anesthesiology. (1995). 83 980–5 [Article] [PubMed]
Strebel, S, Lam, AM, Matta, B, Mayberg, TS, Aaslid, R, Newell, DW Dynamic and static cerebral autoregulation during isoflurane, desflurane, and propofol anesthesia.. Anesthesiology. (1995). 83 66–76 [Article] [PubMed]
Matsukawa, K, Ninomiya, I, Nishiura, N Effects of anesthesia on cardiac and renal sympathetic nerve activities and plasma catecholamines.. Am J Physiol. (1993). 265(4 Pt 2) R792–7 [PubMed]
Rusy, BF, Komai, H Anesthetic depression of myocardial contractility: A review of possible mechanisms.. Anesthesiology. (1987). 67 745–66 [Article] [PubMed]
Go, AS, Mozaffarian, D, Roger, VL, Benjamin, EJ, Berry, JD, Borden, WB, Bravata, DM, Dai, S, Ford, ES, Fox, CS, Franco, S, Fullerton, HJ, Gillespie, C, Hailpern, SM, Heit, JA, Howard, VJ, Huffman, MD, Kissela, BM, Kittner, SJ, Lackland, DT, Lichtman, JH, Lisabeth, LD, Magid, D, Marcus, GM, Marelli, A, Matchar, DB, McGuire, DK, Mohler, ER, Moy, CS, Mussolino, ME, Nichol, G, Paynter, NP, Schreiner, PJ, Sorlie, PD, Stein, J, Turan, TN, Virani, SS, Wong, ND, Woo, D, Turner, MB American Heart Association Statistics Committee and Stroke Statistics Subcommittee, Heart disease and stroke statistics—2013 update: A report from the American Heart Association.. Circulation. (2013). 127 e6–245 [Article] [PubMed]
Roger, VL, Go, AS, Lloyd-Jones, DM, Benjamin, EJ, Berry, JD, Borden, WB, Bravata, DM, Dai, S, Ford, ES, Fox, CS, Fullerton, HJ, Gillespie, C, Hailpern, SM, Heit, JA, Howard, VJ, Kissela, BM, Kittner, SJ, Lackland, DT, Lichtman, JH, Lisabeth, LD, Makuc, DM, Marcus, GM, Marelli, A, Matchar, DB, Moy, CS, Mozaffarian, D, Mussolino, ME, Nichol, G, Paynter, NP, Soliman, EZ, Sorlie, PD, Sotoodehnia, N, Turan, TN, Virani, SS, Wong, ND, Woo, D, Turner, MB American Heart Association Statistics Committee and Stroke Statistics Subcommittee, Heart disease and stroke statistics—2012 update: A report from the American Heart Association.. Circulation. (2012). 125 e2–220 [Article] [PubMed]
Steiner, LA, Johnston, AJ, Czosnyka, M, Chatfield, DA, Salvador, R, Coles, JP, Gupta, AK, Pickard, JD, Menon, DK Direct comparison of cerebrovascular effects of norepinephrine and dopamine in head-injured patients.. Crit Care Med. (2004). 32 1049–54 [Article] [PubMed]
Ogoh, S, Sato, K, Fisher, JP, Seifert, T, Overgaard, M, Secher, NH The effect of phenylephrine on arterial and venous cerebral blood flow in healthy subjects.. Clin Physiol Funct Imaging. (2011). 31 445–51 [Article] [PubMed]
Fig. 1.
Correlation between changes in cardiac output (CO) and cerebral blood flow (CBF) in unanesthetized healthy volunteers during central blood volume alterations.5–9  All data are reported in table 1. The diameter of the dot represents the sample size that is also indicated by the number inside of each dot.
Correlation between changes in cardiac output (CO) and cerebral blood flow (CBF) in unanesthetized healthy volunteers during central blood volume alterations.5–9 All data are reported in table 1. The diameter of the dot represents the sample size that is also indicated by the number inside of each dot.
Fig. 1.
Correlation between changes in cardiac output (CO) and cerebral blood flow (CBF) in unanesthetized healthy volunteers during central blood volume alterations.5–9  All data are reported in table 1. The diameter of the dot represents the sample size that is also indicated by the number inside of each dot.
×
Fig. 2.
Cerebral blood flow in patients diagnosed with chronic heart failure (CHF) before (preintervention) and after (postintervention) various interventions.10–14  The control was from patients without cardiac insufficiency. All data are reported in table 2. Only the studies that reported the control, preintervention, and postintervention values of cerebral blood flow in the units of ml min−1 100 g−1 were included. The dots with the same color are from the same study. The diameter of the dot represents the sample size that is also indicated by the number inside of each dot.
Cerebral blood flow in patients diagnosed with chronic heart failure (CHF) before (preintervention) and after (postintervention) various interventions.10–14 The control was from patients without cardiac insufficiency. All data are reported in table 2. Only the studies that reported the control, preintervention, and postintervention values of cerebral blood flow in the units of ml min−1 100 g−1 were included. The dots with the same color are from the same study. The diameter of the dot represents the sample size that is also indicated by the number inside of each dot.
Fig. 2.
Cerebral blood flow in patients diagnosed with chronic heart failure (CHF) before (preintervention) and after (postintervention) various interventions.10–14  The control was from patients without cardiac insufficiency. All data are reported in table 2. Only the studies that reported the control, preintervention, and postintervention values of cerebral blood flow in the units of ml min−1 100 g−1 were included. The dots with the same color are from the same study. The diameter of the dot represents the sample size that is also indicated by the number inside of each dot.
×
Fig. 3.
The conceptual framework of the integrated regulation of brain perfusion. The cerebrovascular resistance determined by the caliber of the cerebral resistance vessels is regulated by various physiologic processes: (1) cardiac output (CO) likely via sympathetic nervous activity (SNA) and renin–angiotensin–aldosterone (RAA) system, depending on the chronicity of the change in CO,5–19  (2) arterial blood pressure (ABP) and cerebral perfusion pressure (CPP) via cerebral autoregulation,2,71  (3) cerebral metabolic activity via neurovascular coupling,3,76  and (4) arterial blood carbon dioxide (CO2)4,25,71  and oxygen (O2)4  via cerebrovascular reactivity. The SNA regulates cerebral blood flow26–29  and may play a prominent role during acute hypertension and hypercapnia29  as a protective mechanism preventing cerebral overperfusion (dashed line). These various regulatory mechanisms, together with other CBF-regulatory mechanisms that are not specified here such as anesthetic effects, integrate at the level of the cerebral resistance vessels and generate only one consequence, which is the extent of the cerebrovascular resistance and, therefore, jointly regulate brain perfusion. The plateau of the autoregulation curve shifts downward when the CO is reduced and upward when augmented. The position of the plateau is determined by the caliber (R) of the cerebral resistance vessels at high (Rhigh), normal (Rnorm), and low (Rlow) CO. The scale of CO on the right side is smaller than that of CBF on the left side to reflect the lesser extent of change in CBF induced by an alteration of CO.
The conceptual framework of the integrated regulation of brain perfusion. The cerebrovascular resistance determined by the caliber of the cerebral resistance vessels is regulated by various physiologic processes: (1) cardiac output (CO) likely via sympathetic nervous activity (SNA) and renin–angiotensin–aldosterone (RAA) system, depending on the chronicity of the change in CO,5–19 (2) arterial blood pressure (ABP) and cerebral perfusion pressure (CPP) via cerebral autoregulation,2,71 (3) cerebral metabolic activity via neurovascular coupling,3,76 and (4) arterial blood carbon dioxide (CO2)4,25,71 and oxygen (O2)4 via cerebrovascular reactivity. The SNA regulates cerebral blood flow26–29 and may play a prominent role during acute hypertension and hypercapnia29 as a protective mechanism preventing cerebral overperfusion (dashed line). These various regulatory mechanisms, together with other CBF-regulatory mechanisms that are not specified here such as anesthetic effects, integrate at the level of the cerebral resistance vessels and generate only one consequence, which is the extent of the cerebrovascular resistance and, therefore, jointly regulate brain perfusion. The plateau of the autoregulation curve shifts downward when the CO is reduced and upward when augmented. The position of the plateau is determined by the caliber (R) of the cerebral resistance vessels at high (Rhigh), normal (Rnorm), and low (Rlow) CO. The scale of CO on the right side is smaller than that of CBF on the left side to reflect the lesser extent of change in CBF induced by an alteration of CO.
Fig. 3.
The conceptual framework of the integrated regulation of brain perfusion. The cerebrovascular resistance determined by the caliber of the cerebral resistance vessels is regulated by various physiologic processes: (1) cardiac output (CO) likely via sympathetic nervous activity (SNA) and renin–angiotensin–aldosterone (RAA) system, depending on the chronicity of the change in CO,5–19  (2) arterial blood pressure (ABP) and cerebral perfusion pressure (CPP) via cerebral autoregulation,2,71  (3) cerebral metabolic activity via neurovascular coupling,3,76  and (4) arterial blood carbon dioxide (CO2)4,25,71  and oxygen (O2)4  via cerebrovascular reactivity. The SNA regulates cerebral blood flow26–29  and may play a prominent role during acute hypertension and hypercapnia29  as a protective mechanism preventing cerebral overperfusion (dashed line). These various regulatory mechanisms, together with other CBF-regulatory mechanisms that are not specified here such as anesthetic effects, integrate at the level of the cerebral resistance vessels and generate only one consequence, which is the extent of the cerebrovascular resistance and, therefore, jointly regulate brain perfusion. The plateau of the autoregulation curve shifts downward when the CO is reduced and upward when augmented. The position of the plateau is determined by the caliber (R) of the cerebral resistance vessels at high (Rhigh), normal (Rnorm), and low (Rlow) CO. The scale of CO on the right side is smaller than that of CBF on the left side to reflect the lesser extent of change in CBF induced by an alteration of CO.
×
Table 1.
Studies Investigating Simultaneous Changes in Cardiac Output and Cerebral Blood Flow via Central Blood Volume Alteration in Unanesthetized Healthy Volunteers
Studies Investigating Simultaneous Changes in Cardiac Output and Cerebral Blood Flow via Central Blood Volume Alteration in Unanesthetized Healthy Volunteers×
Studies Investigating Simultaneous Changes in Cardiac Output and Cerebral Blood Flow via Central Blood Volume Alteration in Unanesthetized Healthy Volunteers
Table 1.
Studies Investigating Simultaneous Changes in Cardiac Output and Cerebral Blood Flow via Central Blood Volume Alteration in Unanesthetized Healthy Volunteers
Studies Investigating Simultaneous Changes in Cardiac Output and Cerebral Blood Flow via Central Blood Volume Alteration in Unanesthetized Healthy Volunteers×
×
Table 2.
Cerebral Blood Flow at Baseline and/or after Various Interventions in Patients with Chronic Heart Failure
Cerebral Blood Flow at Baseline and/or after Various Interventions in Patients with Chronic Heart Failure×
Cerebral Blood Flow at Baseline and/or after Various Interventions in Patients with Chronic Heart Failure
Table 2.
Cerebral Blood Flow at Baseline and/or after Various Interventions in Patients with Chronic Heart Failure
Cerebral Blood Flow at Baseline and/or after Various Interventions in Patients with Chronic Heart Failure×
×