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Pain Medicine  |   September 2002
Intestinal and Cerebral Oxygenation during Severe Isovolemic Hemodilution and Subsequent Hyperoxic Ventilation in a Pig Model
Author Affiliations & Notes
  • Jasper van Bommel, M.D., Ph.D.
    *
  • Adrianus Trouwborst, M.D., Ph.D.
  • Lothar Schwarte, M.D.
  • Martin Siegemund, M.D.
    §
  • Can Ince, Ph.D.
  • Ch. Pieter Henny, M.D., Ph.D.
    #
  • * Research Associate, Department of Anesthesiology, Erasmus Medical Center, Rotterdam, The Netherlands. † Professor and Chairman, § Senior Research Associate, ∥Professor, # Associate Professor, Department of Anesthesiology, Academic Medical Center, University of Amsterdam. ‡ Research Associate, Department of Anesthesiology, Heinrich-Heine University, Düsseldorf, Germany.
  • Received from the Department of Anesthesiology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Article Information
Pain Medicine
Pain Medicine   |   September 2002
Intestinal and Cerebral Oxygenation during Severe Isovolemic Hemodilution and Subsequent Hyperoxic Ventilation in a Pig Model
Anesthesiology 9 2002, Vol.97, 660-670. doi:
Anesthesiology 9 2002, Vol.97, 660-670. doi:
ACUTE isovolemic hemodilution is a commonly used technique to delay or eliminate the need for transfusion of homologous blood during surgery. Although the oxygen content of the blood is reduced during this procedure, the whole body oxygen consumption (V̇o2) is maintained by an increase in cardiac output and an increase in the oxygen extraction ratio (O2ER) of the tissues. A critical level of hemodilution is reached when the oxygen delivery (Do2) falls below a critical point and compensatory mechanisms become insufficient:V̇o2becomes dependent on supply, decreasing at the same rate as the Do2. Such critical levels of hemodilution have been determined for systemic Do2and V̇o2in anesthetized animals 1–5 and in an anesthetized human patient. 6 In a similar way, a critical level of hemodilution can be determined for an organ system: using an anesthetized rat model, similar critical levels of hemodilution were found for the intestinal oxygen consumption and intestinal microvascular oxygen partial pressure (μPo2). 7 
During hemodilution, a redistribution of cardiac output and oxygen transport occurs in favor of organs with a lower capacity to increase oxygen extraction, i.e.  , heart and brain. 8–11 Other organs, for example, the intestines, are supposed to compensate for the decreased oxygen content of the blood, mainly by an increase in oxygen extraction. 1,12,13 In a similar way, a redistribution of the oxygen flux might occur within an organ during hemodilution. 8,14 Thus, it can be hypothesized that a critical hemodilution level for the systemic V̇o2will not reflect the critical levels of hemodilution for the oxygenation of different organ systems; (parts of) organs that respond differently to a decrease in hematocrit might display different critical levels of hemodilution. Because in Jehovah's Witness patients hyperoxia has been used during critical anemia, we also hypothesized that beyond these critical hemodilution levels, an increase in the arterial oxygen content caused by an increase in the inspired oxygen fraction (Fio2) to 1.0 could restore local and systemic oxygenation.
Based on these hypotheses, the present study was designed to determine the critical levels of hemodilution for the oxygen consumption of the whole body and the intestines. In addition, critical levels were determined for the microvascular oxygenation of the cerebral cortex and the intestinal mucosa and serosa. Comparison of the latter two parameters with the intestinal oxygen consumption was expected to provide more insight into the redistribution of the oxygen flux within the intestines during isovolemic hemodilution. Because in a rat model, which was used in a previous study, 7 only the intestinal oxygenation could be assessed, an anesthetized pig model was used for the present study, with the additional advantage that the responses of this animal to several conditions of stress have been demonstrated to be similar to those of humans. 15,16 
Materials and Methods
Animals
The protocol of the present study was approved by the Animal Research Committee of the Academic Medical Center at the University of Amsterdam. Animal care and handling were performed in accordance with the national guidelines for care of laboratory animals. The experiments were performed in 15 crossbred Landrace x Yorkshire pigs, 10–12 weeks old, with a mean (± SD) body weight of 25 ± 2 kg.
Experimental Preparation
After an overnight fast with free access to water, the animals were sedated with an intramuscular injection of ketamine (20 mg/kg), midazolam (1 mg/kg), and atropine (0.5 mg). Anesthesia was induced with thiopental (5 mg/kg intravenously) and was maintained by intravenous infusion of midazolam (0.2 mg/kg bolus, followed by 0.2 mg · kg−1· h−1) and fentanyl (20 μg/kg bolus, followed by 10 μg · kg−1· h−1). Muscle relaxation was obtained with pancuronium bromide (0.1 mg/kg bolus, followed by 0.1 mg · kg−1· h− 1).
Identical anesthetic protocols have proven to be adequate for similar acute experiments in pigs. 8,14,17,18 One separate time-matched sham-operated animal was anesthetized without the use of muscle relaxants to ensure that the anesthetic regimen was adequate. After tracheal intubation, ventilation was performed (AV-1; Drägerwerke, Lübeck, Germany) with oxygen in air (Fio2, 0.33), maintaining normocapnia. As maintenance fluid, a crystalloid solution (Ringer's lactate) was administered (15 ml · kg−1· h−1). Central body temperature was maintained at approximately 37°C with a heating pad and isolation blankets.
Catheters were placed in the right brachial artery (6 French) for the measurement of arterial blood pressure and collection of arterial blood samples, the right brachial vein (14 gauge) for the administration of fluids, and the left femoral artery (8 French) for blood withdrawal during exchange transfusion. For the collection of jugular venous blood samples, a catheter (4 French) was inserted cranially into the right internal jugular vein in such a way that the tip of the catheter reached at least to the base of the skull. In this way, the internal jugular venous oxygen measurements were assumed to reflect the venous outflow of the brain in the jugular bulb, with a minimum of extracranial contamination. 19 A pulmonary artery thermodilution catheter (Edwards 7 French; Baxter Healthcare Corp., Round Lake, IL) was positioned in the pulmonary artery via  an introducer in the left femoral vein for the measurement of cardiac output, right atrial pressure (RAP), pulmonary artery pressure, pulmonary capillary wedge pressure, central body temperature, and collection of mixed venous blood samples.
Following identification of the right carotid bifurcation, the external carotid artery was ligated immediately distal from the bifurcation, and an ultrasonic flow probe (3.0 mm; Transonic Systems Inc., Ithaca, NY) was placed around the right common carotid artery. If there was any artery branching from the internal carotid artery between the flow probe and the base of the skull (for instance, the occipital artery), this vessel was ligated as well.
Following midline laparotomy, an ultrasonic flow probe (4.0 mm; Transonic Systems Inc.) was placed around the superior mesenteric artery for the measurement of blood flow to the splanchnic region. After location of the terminal ileum, a mesenteric vein related to the ileum was cannulated (6 French) for the collection of mesenteric venous blood samples. An antimesenteric incision was made to expose the intestinal mucosa. The urinary bladder was cannulated to prevent distension of the bladder wall and to monitor urinary production.
A 5 × 5-cm skin flap was removed from the right side of the skull. A circular piece of bone (approximately 2 cm in diameter) was removed, exposing the dura mater of the brain. The dura was opened carefully until the cortical surface of the right hemisphere was clearly visible. Continuous irrigation with warmed saline prevented the exposed tissues from desiccation.
Hemodynamic and Blood Gas Measurements
Systolic and diastolic arterial blood pressures (millimeters of mercury), heart rate (beats per minute), RAP (millimeters of mercury), systolic and diastolic pulmonary pressures (millimeters of mercury), and pulmonary capillary wedge pressure (millimeters of mercury) were monitored. Cardiac output was measured by thermodilution and a cardiac output computer (Vigilance; Baxter Edwards Critical Care, Round Lake, IL). The average of 3 consecutive bolus injections of 5 ml of room-temperature saline was considered representative for the cardiac output at each measurement point. Blood flows in the internal carotid artery (Q̇ICA) and superior mesenteric artery (Q̇SMA) were measured continuously (Flow meter T206; Transonic Systems Inc.). By distal occlusion of the vessels, zero flow values were obtained, which were compared with the values measured at the end of the experiment after the animal had been killed. Hemodynamic values were indexed according to body weight. Systemic vascular resistance index, mesenteric vascular resistance index, and internal carotid vascular resistance index (all millimeters of mercury per milliliter per minute per kilogram) were calculated as follows: (MAP − RAP)/CI, (MAP − RAP)/Q̇SMA, and (MAP − RAP)/Q̇ICA, respectively, where MAP = mean arterial pressure.
At each measurement point, simultaneously an arterial sample was taken from the brachial artery, a mixed venous sample from the pulmonary artery catheter, a mesenteric venous sample from the mesenteric venous catheter, and a jugular venous sample from the internal jugular venous catheter. The samples were used to determine blood gas values (ABL505; Radiometer, Copenhagen, Denmark), as well as hematocrit, hemoglobin concentration, and hemoglobin oxygen saturation (So2) (OSM 3; Radiometer), corrected for species.
Systemic Do2 (Do2SYS; milliliters per minute per kilogram body weight) was calculated as:EQUATION
where CI is expressed as milliliters per minute per kilogram, and arterial oxygen content is expressed as milliliters oxygen per milliliter blood, which was calculated as:EQUATION
where Pao2is arterial oxygen partial pressure and Sao2is arterial oxygen saturation. Systemic oxygen consumption (V̇o2SYS; milliliters per minute per kilogram bodyweight) was calculated as:EQUATION
The systemic O2ER (O2ERSYS; percent) was calculated as:EQUATION
In a similar way, the intestinal Do2(DO2SMA), V̇o2(V̇o2SMA), and O2ER (O2ERSMA) were calculated. Measurement of the internal jugular venous oxygen content allowed the calculation of the arteriovenous oxygen content difference, and thereby the O2ER of the brain 20–22 (O2ERICA) was calculated as:EQUATION
Microvascular Oxygen Partial Pressure Measurements
The μPo2was measured in the cerebral cortex and the serosa and mucosa of the ileum, using the oxygen-dependent quenching of Pd-porphyrin phosphorescence. Excitation of Pd-porphyrin by a pulse of light causes emission of phosphorescence with a decay in time, which is quantitatively related to the oxygen concentration. 23–25 Pd-meso-tetra(4 carboxy-phenyl)porphine (Porphyrin Products, Logan, UT) is coupled to human serum albumin to form a large molecular complex that, when injected intravenously, is confined mainly to the vascular compartment. 25,26 Fifty milliliters of a 4-mm Pd-porphyrin solution was administered, corresponding with a dosage of 12 mg/kg bodyweight. The μ Po2measurements were made with optical fibers for the transmission of excitation and emission light, attached to a phosphorimeter. To determine which microvascular compartment is measured by fiber phosphorimetry, the Pd-porphyrin phosphorescence fiber technique has been compared with a microscopic phosphorimeter: simultaneous Po2measurements with the fiberoptic technique showed excellent correlation with microscopically measured Po2in capillaries and first-order venules, but not with arteriolar or venous Po2values, at different Fio2levels. 27 Thus, this result allowed us to term the fiberoptic measurement of Po2as the measurement of μPo2. Fiberoptic measurements of μPo2incorporate blood vessels over an area of approximately 1 cm2with a penetration depth of approximately 0.5 mm. 17,25 As the calibration constants in the calculation of the μPo2from the phosphorescence decay time are temperature dependent, intestinal surface temperature measurements were used for correction of these constants. In the present study, a multifiber phosphorimeter was used, with three separately operated optical fibers. The fibers were placed near the surfaces of the cerebral cortex and the serosa and mucosa of the ileum. In this way, the μ Po2was measured in three different regions simultaneously.
Experimental Procedure
After preparation and a stabilization period of at least 30 min, two baseline measurements were made during a 1-h period. The animals were randomized between a hemodilution group (n = 10) and a time-matched control group (n = 5). Stepwise isovolemic hemodilution was accomplished by withdrawal of blood from the femoral artery and simultaneous administration of an equal volume of HAES-steril 6% (6% hydroxyethylstarch, degree of substitution 0.5, in 0.9% NaCl solution, Mw 200,000; Fresenius, Germany) through the femoral vein at the same rate. Four dilution steps were made: three steps of 20 ml/kg bodyweight and a final step of 30 ml/kg, resulting in a total volume exchange of 90 ml/kg. Twenty minutes after each hemodilution step, all hemodynamic, blood gas, and μPo2measurements were repeated. Lactate measurements were performed at baseline and after a total volume exchange of 40 and 90 ml/kg. Following the measurements after the final hemodilution step, Fio2was increased to 1.0, and after 20 min stabilization, all measurements were repeated. In the control group, identical measurements were made at corresponding time intervals, but no hemodilution was performed. In the final stage of the experiment, the Fio2was increased to 1.0. All experiments were terminated by administration of 30 mmol of potassium chloride.
Statistical Analysis
Values are reported as mean ± SD. Because the consecutive baseline measurements were not significantly different for any parameter, they were averaged and presented as a single data point. Intragroup differences were analyzed using analysis of variance for repeated measurements. When appropriate, post hoc  analyses were performed with the Student-Newman-Keuls test. Intergroup differences for each measurement point were analyzed with the unpaired t  test; Bonferroni correction for multiple comparisons was used. P  values < 0.05 were considered significant. A critical level of hemodilution was determined for the whole body V̇o2and the μPo2of the intestinal serosa and mucosa and the cerebral cortex. From plots of hematocrit against V̇o2SYSand μ Po2, it was possible to determine the points at which V̇o2or μPo2became dependent on the hematocrit with further hemodilution. These points were determined for each animal separately by the intersection of the two best-fit regression lines, as determined by a least sum of squares technique.
Results
Systemic and Pulmonary Hemodynamics
Because of the type of measurements, muscle relaxation was necessary throughout the experimental protocol. To ensure that the anesthetic regimen was sound, one separate time-matched sham-operated animal was anesthetized without the use of muscle relaxants. Throughout the experiment, the animal did not try to escape or move purposefully. Only slight shivering was observed 150 min after start of anesthesia. All hemodynamic parameters remained stable as in all control group animals. All hemodynamics of the study animals are summarized in table 1.
Table 1. Hemodynamic Measurements during Isovolemic Hemodilution and Hyperoxia
Image not available
Table 1. Hemodynamic Measurements during Isovolemic Hemodilution and Hyperoxia
×
Baseline measurements in the hemodilution and the control groups were not significantly different, except for the heart rate, which was lower in the control group. In the control animals, all systemic hemodynamic parameters remained constant throughout the experiment. In the hemodilution group, the decrease in hematocrit, from 25.3 ± 3.0 at baseline to 7.6 ± 1.2% after exchange of 90 ml/kg, was accompanied by an increase in cardiac index (CI;fig. 1). Heart rate increased significantly, whereas stroke volume did not change from baseline values. MAP remained constant during hemodilution, although the systemic vascular resistance index decreased significantly compared with baseline and control group values. The pulmonary artery pressure, vascular resistance index, and pulmonary capillary wedge pressure did not change significantly during hemodilution.
Fig. 1. Systemic blood flow and oxygenation parameters after 20, 40, 60, and 90 ml/kg hemodilution (with hematocrit values) and consequent hyperoxic ventilation (HO, beyond dotted line) in 10 anesthetized pigs (HD) and at corresponding time points in 5 control animals (Co). Cardiac index (CI) increased during hemodilution. Systemic oxygen delivery (Do2SYS) decreased with the onset of hemodilution, whereas the systemic oxygen consumption (V̇o2SYS) decreased after the final hemodilution step. Systemic oxygen extraction ratio (O2ERSYS) increased significantly. Hyperoxia had no significant effect on these parameters. Values represent mean ± SD. *P  < 0.05 HD versus  Co; ˆP  < 0.05 HD versus  baseline; ⧫P  < 0.05 HD versus  previous.
Fig. 1. Systemic blood flow and oxygenation parameters after 20, 40, 60, and 90 ml/kg hemodilution (with hematocrit values) and consequent hyperoxic ventilation (HO, beyond dotted line) in 10 anesthetized pigs (HD) and at corresponding time points in 5 control animals (Co). Cardiac index (CI) increased during hemodilution. Systemic oxygen delivery (Do2SYS) decreased with the onset of hemodilution, whereas the systemic oxygen consumption (V̇o2SYS) decreased after the final hemodilution step. Systemic oxygen extraction ratio (O2ERSYS) increased significantly. Hyperoxia had no significant effect on these parameters. Values represent mean ± SD. *P 
	< 0.05 HD versus 
	Co; ˆP 
	< 0.05 HD versus 
	baseline; ⧫P 
	< 0.05 HD versus 
	previous.
Fig. 1. Systemic blood flow and oxygenation parameters after 20, 40, 60, and 90 ml/kg hemodilution (with hematocrit values) and consequent hyperoxic ventilation (HO, beyond dotted line) in 10 anesthetized pigs (HD) and at corresponding time points in 5 control animals (Co). Cardiac index (CI) increased during hemodilution. Systemic oxygen delivery (Do2SYS) decreased with the onset of hemodilution, whereas the systemic oxygen consumption (V̇o2SYS) decreased after the final hemodilution step. Systemic oxygen extraction ratio (O2ERSYS) increased significantly. Hyperoxia had no significant effect on these parameters. Values represent mean ± SD. *P  < 0.05 HD versus  Co; ˆP  < 0.05 HD versus  baseline; ⧫P  < 0.05 HD versus  previous.
×
Hyperoxia decreased the heart rate to the range of baseline values, resulting in a slight but not significant decrease in CI. In addition, the pulmonary capillary wedge pressure and the systemic vascular resistance index increased after hyperoxia.
Systemic Oxygenation
Data are summarized in table 2and figure 1. Despite the increase in CI, Do2SYSdecreased with the onset of hemodilution. The O2ERSYSincreased, and as a result the V̇o2SYSwas preserved through a hematocrit of 9.9% but decreased significantly after the final hemodilution step at a hematocrit of 7.6%. Consequently, the mixed venous Po2and So2decreased with progressive hemodilution.
Table 2. Systemic Blood Gas and Lactate Measurements during Isovolemic Hemodilution and Hyperoxia
Image not available
Table 2. Systemic Blood Gas and Lactate Measurements during Isovolemic Hemodilution and Hyperoxia
×
Following the final dilution step, hyperoxia significantly increased the arterial oxygen content in the hemodilution group from 3.4 ± 0.3 to 4.7 ± 0.5 ml/dl. This did not change Do2SYS, despite the decrease in CI. The O2ERSYSdecreased significantly following hyperoxia, and V̇o2SYSwas not restored. Mixed venous Po2and So2increased above baseline values (P  < 0.05). In the control group, the arterial oxygen content was increased by hyperoxia as well. However, this did not change the Do2SYSand V̇o2SYS, although mixed venous Po2and So2exceeded baseline values.
Regional Blood Flow and Oxygenation
Although all animals underwent the same surgical and anesthetic protocols and were randomly assigned to the hemodilution or the control group, mesenteric blood flow (Q̇SMA) in the control group was lower (fig. 2) compared with the hemodilution group. All control group parameters remained constant. Hemodilution did not change Q̇SMA, resulting in a progressive decrease in Do2SMA. After exchange of 60 ml/kg (corresponding hematocrit, 9.9%), V̇o2SMAwas decreased from baseline, whereas O2ERSMAincreased from 21 ± 7% at baseline to 46 ± 9% after the final hemodilution step (fig. 2).
Fig. 2. Intestinal blood flow and oxygenation parameters after 20, 40, 60, and 90 ml/kg hemodilution (with hematocrit values) and consequent hyperoxic ventilation (HO, beyond dotted line) in 10 anesthetized pigs (HD) and at corresponding time points in 5 control animals (Co). Superior mesenteric artery blood flow (Q̇SMA) did not change during hemodilution. Superior mesenteric artery oxygen delivery (Do2SMA) decreased with the onset of hemodilution; V̇o2SMAdecreased after the third hemodilution step. Superior mesenteric artery oxygen extraction ratio (O2ERSMA) increased progressively during the experiment. Hyperoxia significantly decreased Q̇SMAand Do2SMAin the control group and O2ERSMAin the hemodilution group. Values represent mean ± SD.*P  < 0.05 HD versus  Co; ˆP  < 0.05 HD versus  baseline; ⧫P  < 0.05 HD versus  previous.
Fig. 2. Intestinal blood flow and oxygenation parameters after 20, 40, 60, and 90 ml/kg hemodilution (with hematocrit values) and consequent hyperoxic ventilation (HO, beyond dotted line) in 10 anesthetized pigs (HD) and at corresponding time points in 5 control animals (Co). Superior mesenteric artery blood flow (Q̇SMA) did not change during hemodilution. Superior mesenteric artery oxygen delivery (Do2SMA) decreased with the onset of hemodilution; V̇o2SMAdecreased after the third hemodilution step. Superior mesenteric artery oxygen extraction ratio (O2ERSMA) increased progressively during the experiment. Hyperoxia significantly decreased Q̇SMAand Do2SMAin the control group and O2ERSMAin the hemodilution group. Values represent mean ± SD.*P 
	< 0.05 HD versus 
	Co; ˆP 
	< 0.05 HD versus 
	baseline; ⧫P 
	< 0.05 HD versus 
	previous.
Fig. 2. Intestinal blood flow and oxygenation parameters after 20, 40, 60, and 90 ml/kg hemodilution (with hematocrit values) and consequent hyperoxic ventilation (HO, beyond dotted line) in 10 anesthetized pigs (HD) and at corresponding time points in 5 control animals (Co). Superior mesenteric artery blood flow (Q̇SMA) did not change during hemodilution. Superior mesenteric artery oxygen delivery (Do2SMA) decreased with the onset of hemodilution; V̇o2SMAdecreased after the third hemodilution step. Superior mesenteric artery oxygen extraction ratio (O2ERSMA) increased progressively during the experiment. Hyperoxia significantly decreased Q̇SMAand Do2SMAin the control group and O2ERSMAin the hemodilution group. Values represent mean ± SD.*P  < 0.05 HD versus  Co; ˆP  < 0.05 HD versus  baseline; ⧫P  < 0.05 HD versus  previous.
×
Baseline values for the carotid blood flow (Q̇ICA;fig. 3) and the corresponding vascular resistance (table 1) were comparable for both groups. Q̇ICAincreased from 2.5 ± 0.5 ml · min−1· kg−1at baseline to 4.2 ± 0.6 ml · min−1· kg− 1after exchange of 90 ml/kg (fig. 3). Internal jugular venous Po2(fig. 4) and So2(table 3) decreased during hemodilution, reflecting the increase in O2ERICA(from 30 ± 6% at baseline to 47 ± 6% at 90-ml/kg exchange;fig. 3). Mesenteric venous Po2(fig. 4) and So2values (table 3) decreased in a similar way.
Fig. 3. Internal carotid artery blood flow (Q̇ICA) and cerebral oxygen extraction ratio (O2ERICA) after 20, 40, 60, and 90 ml/kg hemodilution (with hematocrit values) and consequent hyperoxic ventilation (HO, beyond dotted line) in 10 anesthetized pigs (HD) and at corresponding time points in 5 control animals (Co). Q̇ICAincreased after the first hemodilution step, O2ERICAafter the third hemodilution step. Hyperoxia had no significant effect on these parameters. Values represent mean ± SD. *P  < 0.05 HD versus  Co; ˆP  < 0.05 HD versus  baseline; ⧫P  < 0.05 HD versus  previous.
Fig. 3. Internal carotid artery blood flow (Q̇ICA) and cerebral oxygen extraction ratio (O2ERICA) after 20, 40, 60, and 90 ml/kg hemodilution (with hematocrit values) and consequent hyperoxic ventilation (HO, beyond dotted line) in 10 anesthetized pigs (HD) and at corresponding time points in 5 control animals (Co). Q̇ICAincreased after the first hemodilution step, O2ERICAafter the third hemodilution step. Hyperoxia had no significant effect on these parameters. Values represent mean ± SD. *P 
	< 0.05 HD versus 
	Co; ˆP 
	< 0.05 HD versus 
	baseline; ⧫P 
	< 0.05 HD versus 
	previous.
Fig. 3. Internal carotid artery blood flow (Q̇ICA) and cerebral oxygen extraction ratio (O2ERICA) after 20, 40, 60, and 90 ml/kg hemodilution (with hematocrit values) and consequent hyperoxic ventilation (HO, beyond dotted line) in 10 anesthetized pigs (HD) and at corresponding time points in 5 control animals (Co). Q̇ICAincreased after the first hemodilution step, O2ERICAafter the third hemodilution step. Hyperoxia had no significant effect on these parameters. Values represent mean ± SD. *P  < 0.05 HD versus  Co; ˆP  < 0.05 HD versus  baseline; ⧫P  < 0.05 HD versus  previous.
×
Fig. 4. Intestinal serosal and mucosal, and cerebral cortex microvascular oxygen partial pressure (μPo2) and mesenteric and jugular venous Po2values after 20, 40, 60, and 90 ml/kg hemodilution (with hematocrit values) and consequent hyperoxic ventilation (HO, beyond dotted line) in 10 anesthetized pigs (HD) and at corresponding time points in 5 control animals (Co). Serosal μPo2decreased significantly after the second hemodilution step, whereas the mucosal μ Po2fell after 60 ml/kg blood exchange. Mesenteric venous Po2decreased throughout the complete hemodilution procedure. Cerebral μPo2decreased significantly after the third hemodilution step, similar to the internal jugular venous Po2. Hyperoxia increased all μPo2values and raised the venous Po2above baseline levels in the hemodilution group but had no significant effect on these parameters in the control group. Values represent mean ± SD. *P  < 0.05 HD versus  Co; ˆP  < 0.05 HD versus  baseline; ⧫P  < 0.05 HD versus  previous.
Fig. 4. Intestinal serosal and mucosal, and cerebral cortex microvascular oxygen partial pressure (μPo2) and mesenteric and jugular venous Po2values after 20, 40, 60, and 90 ml/kg hemodilution (with hematocrit values) and consequent hyperoxic ventilation (HO, beyond dotted line) in 10 anesthetized pigs (HD) and at corresponding time points in 5 control animals (Co). Serosal μPo2decreased significantly after the second hemodilution step, whereas the mucosal μ Po2fell after 60 ml/kg blood exchange. Mesenteric venous Po2decreased throughout the complete hemodilution procedure. Cerebral μPo2decreased significantly after the third hemodilution step, similar to the internal jugular venous Po2. Hyperoxia increased all μPo2values and raised the venous Po2above baseline levels in the hemodilution group but had no significant effect on these parameters in the control group. Values represent mean ± SD. *P 
	< 0.05 HD versus 
	Co; ˆP 
	< 0.05 HD versus 
	baseline; ⧫P 
	< 0.05 HD versus 
	previous.
Fig. 4. Intestinal serosal and mucosal, and cerebral cortex microvascular oxygen partial pressure (μPo2) and mesenteric and jugular venous Po2values after 20, 40, 60, and 90 ml/kg hemodilution (with hematocrit values) and consequent hyperoxic ventilation (HO, beyond dotted line) in 10 anesthetized pigs (HD) and at corresponding time points in 5 control animals (Co). Serosal μPo2decreased significantly after the second hemodilution step, whereas the mucosal μ Po2fell after 60 ml/kg blood exchange. Mesenteric venous Po2decreased throughout the complete hemodilution procedure. Cerebral μPo2decreased significantly after the third hemodilution step, similar to the internal jugular venous Po2. Hyperoxia increased all μPo2values and raised the venous Po2above baseline levels in the hemodilution group but had no significant effect on these parameters in the control group. Values represent mean ± SD. *P  < 0.05 HD versus  Co; ˆP  < 0.05 HD versus  baseline; ⧫P  < 0.05 HD versus  previous.
×
Table 3. Regional Venous Blood Gas and Lactate Measurements during Hemodilution and Hyperoxia
Image not available
Table 3. Regional Venous Blood Gas and Lactate Measurements during Hemodilution and Hyperoxia
×
Hyperoxia did not influence Q̇SMAafter hemodilution. The Do2SMAincreased slightly but not significantly, and V̇o2SMAdid not improve. Mesenteric venous Po2and So2increased substantially following hyperoxia; the Po2even exceeded baseline values. In the control group, however, the mesenteric vascular resistance index increased after hyperoxia and the Q̇SMAdecreased, resulting in a decrease in Do2SMAbut not in V̇o2SMA. The change in O2ERSMAwas not statistically significant, and the mesenteric venous Po2and So2did not significantly increase after hyperoxia in the control group.
Hyperoxia decreased the Q̇ICAsignificantly in the hemodilution and the control groups. Po2and So2in the internal jugular vein in the hemodilution group exceeded baseline values, whereas they did not change in the control group.
Microvascular Oxygen Partial Pressure Measurements
Microvascular and regional venous Po2measurements are shown in figure 4. Baseline measurements were similar for the hemodilution and the control groups. The μPo2of the serosa (59 ± 7 mmHg at baseline) decreased at the second hemodilution step and fell to 21 ± 7 mmHg after the last step (hematocrit, 7.6 ± 1.2%). The mucosal μPo2(27 ± 4 mmHg at baseline) remained unaffected for a longer period of time and was decreased after the third hemodilution step (hematocrit, 9.9 ± 1.1%). The μ Po2of the cerebral cortex (26 ± 3 mmHg at baseline) demonstrated a similar behavior as the mucosal μPo2and was also decreased after the third hemodilution step. μPo2measurements in the control groups did not change in time.
In the hemodilution group, hyperoxia increased both the serosal and the mucosal μPo2; the mucosal μ Po2was even restored to baseline values. The cerebral cortex μPo2was also significantly increased but did not return to baseline values. Hyperoxia had no significant effect in the control group.
Critical Levels of Hemodilution
The critical hematocrit levels for the systemic V̇o2and intestinal and cerebral μPo2measurements are shown in figure 5. V̇o2SYS(fig. 5A) started to decrease with hemodilution at an average hematocrit of 13.7 ± 3.5%. In the intestines, the critical hematocrit for the intestinal mucosa (fig. 5B) was 11.4 ± 2.6%, whereas the serosal μPo2(fig. 5C) started to decrease with hematocrit already at an average value of 16.9 ± 4.2. The μPo2in the cerebral cortex (fig. 5D) displayed a similar behavior as the intestinal mucosa and V̇o2SYSand started to decrease with hematocrit at an average value of 12.1 ± 3.1%. The critical hematocrit values for the mucosal and cerebral μPo2and V̇o2SYSwere not significantly different; compared with the serosal μPo2, the critical hematocrit of the latter was found to be significantly higher.
Fig. 5. (A  ) Critical levels of hemodilution for the systemic oxygen consumption (V̇o2), calculated for the hematocrit. The critical values were determined for each animal separately, resulting in an average critical hematocrit of 13.7 ± 3.5%. (B  ) Critical levels of hemodilution for the mucosal microvascular oxygen partial pressure (μ Po2), calculated for the hematocrit. The critical values were determined for each animal separately, resulting in an average critical hematocrit of 11.4 ± 2.6%. (C  ) Critical levels of hemodilution for the serosal μPo2, calculated for the hematocrit. The critical values were determined for each animal separately, resulting in an average critical hematocrit of 16.9 ± 4.2%, which was significantly higher than the critical hematocrit values of the mucosal and cerebral μPo2and systemic V̇o2. (D  ) Critical levels of hemodilution for the cerebral cortex μPo2, calculated for the hematocrit. The critical values were determined for each animal separately, resulting in an average critical hematocrit of 12.1 ± 3.1%.
Fig. 5. (A 
	) Critical levels of hemodilution for the systemic oxygen consumption (V̇o2), calculated for the hematocrit. The critical values were determined for each animal separately, resulting in an average critical hematocrit of 13.7 ± 3.5%. (B 
	) Critical levels of hemodilution for the mucosal microvascular oxygen partial pressure (μ Po2), calculated for the hematocrit. The critical values were determined for each animal separately, resulting in an average critical hematocrit of 11.4 ± 2.6%. (C 
	) Critical levels of hemodilution for the serosal μPo2, calculated for the hematocrit. The critical values were determined for each animal separately, resulting in an average critical hematocrit of 16.9 ± 4.2%, which was significantly higher than the critical hematocrit values of the mucosal and cerebral μPo2and systemic V̇o2. (D 
	) Critical levels of hemodilution for the cerebral cortex μPo2, calculated for the hematocrit. The critical values were determined for each animal separately, resulting in an average critical hematocrit of 12.1 ± 3.1%.
Fig. 5. (A  ) Critical levels of hemodilution for the systemic oxygen consumption (V̇o2), calculated for the hematocrit. The critical values were determined for each animal separately, resulting in an average critical hematocrit of 13.7 ± 3.5%. (B  ) Critical levels of hemodilution for the mucosal microvascular oxygen partial pressure (μ Po2), calculated for the hematocrit. The critical values were determined for each animal separately, resulting in an average critical hematocrit of 11.4 ± 2.6%. (C  ) Critical levels of hemodilution for the serosal μPo2, calculated for the hematocrit. The critical values were determined for each animal separately, resulting in an average critical hematocrit of 16.9 ± 4.2%, which was significantly higher than the critical hematocrit values of the mucosal and cerebral μPo2and systemic V̇o2. (D  ) Critical levels of hemodilution for the cerebral cortex μPo2, calculated for the hematocrit. The critical values were determined for each animal separately, resulting in an average critical hematocrit of 12.1 ± 3.1%.
×
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×
Metabolic Parameters
Systemic and regional parameters are summarized in tables 2 and 3, respectively. Arterial carbon dioxide partial pressure did not change during the entire experiment in the hemodilution and the control groups. The systemic and regional venous p  H measurements did not change in the control group. In the hemodilution group, the arterial p  H decreased significantly after the final hemodilution step. The mixed venous p  H did not change, but the mesenteric venous p  H decreased after the second step and the jugular venous p  H after the third step. There was no significant change in systemic and regional lactate levels during hemodilution.
Discussion
The main finding of this study is that the systemic V̇o2, the cerebral μPo2, and the intestinal mucosal μPo2became impaired at the same stage during hemodilution, whereas the intestinal serosal μ Po2became impaired at an earlier stage. The systemic response to the decreased arterial oxygen content consisted of an increase in CI and an increase in O2ERSYS. At a regional level, the increased CI was redistributed in favor of other organ systems than the intestines, as Q̇SMAremained constant. Despite the redistribution of blood flow, systemic as well as intestinal V̇o2became impaired by the diminished oxygen supply at the same level of hemodilution. Although systemic redistribution may have favored the oxygenation of, for instance, the brain, the intestines successfully compensated for the diminished Do2by a larger increase in the oxygen extraction from the blood: 130% increase for the intestinal versus  52% for the cerebral O2ER from baseline to the final hemodilution step. An increase in O2ER as the predominant mechanism for the preservation of intestinal V̇o2has been reported in previous studies as well. 1,12,28 Finally, a level of hemodilution was reached below which all compensatory mechanisms became insufficient, resulting in a general critical level of hemodilution for the whole body, the intestinal mucosa, and the cerebral cortex.
Redistribution of a diminished oxygen supply in favor of organ systems with a lower oxygen extraction capacity can increase the efficiency of Do2. 29 However, the mechanisms behind the redistribution of blood flow during hemodilution are not clear. The results of the present study demonstrated the functional consequences of redistribution and only allow for speculations to be made regarding regulatory mechanisms. Possible mechanisms that could account for systemic or local redistribution could include increased sympathetic activity, 30–32 although the level of circulating catecholamines does not increase during hemodilution. 8 On the other hand, activity of nitric oxide might play an important role in the systemic and splanchnic response to hemodilution. 33–35 An increase in cerebral blood flow during hemodilution has been attributed to decreases in arterial oxygen concentration and blood viscosity 36–38; increased nitric oxide activity should not be involved in this process. 39 
Although the V̇o2SMAand the mucosal μPo2were preserved until a hematocrit of ±11.0%, the serosal μPo2started to decline at a hematocrit of 17.0% (P  < 0.05). This finding implies that the mucosa contains the predominant oxygen-consuming part of the intestinal wall and is in agreement with the oxygen electrode measurements of Haisjackl et al.  14 during hemodilution. Being the site for absorption and secretion in the gastrointestinal tract and the barrier to microbial invasion from the intestinal lumen, the gut mucosa can be expected to have a greater oxygen demand than the serosa. To preserve these important functions during conditions of diminished oxygen supply, it is not unlikely that during hemodilution the diminished intestinal oxygen supply was redistributed in favor of the mucosa. 14,35 A redistribution of intraorgan blood flow during hemodilution has been shown to occur in the heart 8,40,41 and the kidney. 8 
In the present study, systemic and regional oxygenation became impaired in the hematocrit range of 10–15%, which is in agreement with critical values in previous studies. 2,4,6 In addition, the constant regional and systemic lactate concentrations in the present study point at adequate tissue oxygenation until this level of hemodilution, 42 to which is contributed by the values of the regional intestinal carbon dioxide partial pressure. At the lowest hematocrit levels, only the decreased p  H values indicated that tissue oxygenation was impaired, although systemic or regional acidosis did not occur. Considering critical levels of hemodilution in general, it must be noted that anesthetized animals respond differently to hemodilution as compared with conscious animals. Although not supported by the results of the present study, in anesthetized animals cardiac output increased mainly because of an increase in stroke volume, whereas in conscious animals the increased cardiac output was attributable to an increment in heart rate. 43 The influence of anesthesia is emphasized by studies in which a critical level of Do2could not be demonstrated during hemodilution in conscious animals and humans. 44–46 
The increase in Fio2did not improve systemic or intestinal V̇o2despite an increase in arterial oxygen content in the hemodilution and the control groups. Furthermore, it was found that only at low hematocrit levels did hyperoxia increase the regional venous Po2values far more than the μPo2values, indicating that in combination with severe hemodilution, the increased amount of physically dissolved oxygen was being shunted to the venous side of the organ vascular beds. It can be hypothesized that an interaction between the physiologic responses to hemodilution (e.g.  , increased capillary density and blood flow) on the one hand and hyperoxia (reduced capillary density and blood flow 47) on the other hand resulted in at least a partial diversion of the dissolved oxygen away from the microcirculation.
In conclusion, similar critical levels of hemodilution were found for V̇o2SYSand the cerebral and intestinal mucosal μPo2, whereas the intestinal O2ER increased to a greater extent than the cerebral O2ER, indicating that during hemodilution the diminished oxygen supply was efficiently redistributed in favor of the organs with a lower capacity to increase oxygen extraction. The serosal μPo2decreased at an earlier stage than the mucosal μPo2, suggesting that the decreased intestinal oxygen supply was redistributed within the intestinal wall during hemodilution. During oxygen supply dependency, hyperoxic ventilation did not improve systemic or regional V̇o2. The increased regional venous Po2values in combination with the decreased O2ER indicate that the increased amount of physically dissolved oxygen was shunted to the venous side of the organ vascular beds during severe hemodilution.
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Fig. 1. Systemic blood flow and oxygenation parameters after 20, 40, 60, and 90 ml/kg hemodilution (with hematocrit values) and consequent hyperoxic ventilation (HO, beyond dotted line) in 10 anesthetized pigs (HD) and at corresponding time points in 5 control animals (Co). Cardiac index (CI) increased during hemodilution. Systemic oxygen delivery (Do2SYS) decreased with the onset of hemodilution, whereas the systemic oxygen consumption (V̇o2SYS) decreased after the final hemodilution step. Systemic oxygen extraction ratio (O2ERSYS) increased significantly. Hyperoxia had no significant effect on these parameters. Values represent mean ± SD. *P  < 0.05 HD versus  Co; ˆP  < 0.05 HD versus  baseline; ⧫P  < 0.05 HD versus  previous.
Fig. 1. Systemic blood flow and oxygenation parameters after 20, 40, 60, and 90 ml/kg hemodilution (with hematocrit values) and consequent hyperoxic ventilation (HO, beyond dotted line) in 10 anesthetized pigs (HD) and at corresponding time points in 5 control animals (Co). Cardiac index (CI) increased during hemodilution. Systemic oxygen delivery (Do2SYS) decreased with the onset of hemodilution, whereas the systemic oxygen consumption (V̇o2SYS) decreased after the final hemodilution step. Systemic oxygen extraction ratio (O2ERSYS) increased significantly. Hyperoxia had no significant effect on these parameters. Values represent mean ± SD. *P 
	< 0.05 HD versus 
	Co; ˆP 
	< 0.05 HD versus 
	baseline; ⧫P 
	< 0.05 HD versus 
	previous.
Fig. 1. Systemic blood flow and oxygenation parameters after 20, 40, 60, and 90 ml/kg hemodilution (with hematocrit values) and consequent hyperoxic ventilation (HO, beyond dotted line) in 10 anesthetized pigs (HD) and at corresponding time points in 5 control animals (Co). Cardiac index (CI) increased during hemodilution. Systemic oxygen delivery (Do2SYS) decreased with the onset of hemodilution, whereas the systemic oxygen consumption (V̇o2SYS) decreased after the final hemodilution step. Systemic oxygen extraction ratio (O2ERSYS) increased significantly. Hyperoxia had no significant effect on these parameters. Values represent mean ± SD. *P  < 0.05 HD versus  Co; ˆP  < 0.05 HD versus  baseline; ⧫P  < 0.05 HD versus  previous.
×
Fig. 2. Intestinal blood flow and oxygenation parameters after 20, 40, 60, and 90 ml/kg hemodilution (with hematocrit values) and consequent hyperoxic ventilation (HO, beyond dotted line) in 10 anesthetized pigs (HD) and at corresponding time points in 5 control animals (Co). Superior mesenteric artery blood flow (Q̇SMA) did not change during hemodilution. Superior mesenteric artery oxygen delivery (Do2SMA) decreased with the onset of hemodilution; V̇o2SMAdecreased after the third hemodilution step. Superior mesenteric artery oxygen extraction ratio (O2ERSMA) increased progressively during the experiment. Hyperoxia significantly decreased Q̇SMAand Do2SMAin the control group and O2ERSMAin the hemodilution group. Values represent mean ± SD.*P  < 0.05 HD versus  Co; ˆP  < 0.05 HD versus  baseline; ⧫P  < 0.05 HD versus  previous.
Fig. 2. Intestinal blood flow and oxygenation parameters after 20, 40, 60, and 90 ml/kg hemodilution (with hematocrit values) and consequent hyperoxic ventilation (HO, beyond dotted line) in 10 anesthetized pigs (HD) and at corresponding time points in 5 control animals (Co). Superior mesenteric artery blood flow (Q̇SMA) did not change during hemodilution. Superior mesenteric artery oxygen delivery (Do2SMA) decreased with the onset of hemodilution; V̇o2SMAdecreased after the third hemodilution step. Superior mesenteric artery oxygen extraction ratio (O2ERSMA) increased progressively during the experiment. Hyperoxia significantly decreased Q̇SMAand Do2SMAin the control group and O2ERSMAin the hemodilution group. Values represent mean ± SD.*P 
	< 0.05 HD versus 
	Co; ˆP 
	< 0.05 HD versus 
	baseline; ⧫P 
	< 0.05 HD versus 
	previous.
Fig. 2. Intestinal blood flow and oxygenation parameters after 20, 40, 60, and 90 ml/kg hemodilution (with hematocrit values) and consequent hyperoxic ventilation (HO, beyond dotted line) in 10 anesthetized pigs (HD) and at corresponding time points in 5 control animals (Co). Superior mesenteric artery blood flow (Q̇SMA) did not change during hemodilution. Superior mesenteric artery oxygen delivery (Do2SMA) decreased with the onset of hemodilution; V̇o2SMAdecreased after the third hemodilution step. Superior mesenteric artery oxygen extraction ratio (O2ERSMA) increased progressively during the experiment. Hyperoxia significantly decreased Q̇SMAand Do2SMAin the control group and O2ERSMAin the hemodilution group. Values represent mean ± SD.*P  < 0.05 HD versus  Co; ˆP  < 0.05 HD versus  baseline; ⧫P  < 0.05 HD versus  previous.
×
Fig. 3. Internal carotid artery blood flow (Q̇ICA) and cerebral oxygen extraction ratio (O2ERICA) after 20, 40, 60, and 90 ml/kg hemodilution (with hematocrit values) and consequent hyperoxic ventilation (HO, beyond dotted line) in 10 anesthetized pigs (HD) and at corresponding time points in 5 control animals (Co). Q̇ICAincreased after the first hemodilution step, O2ERICAafter the third hemodilution step. Hyperoxia had no significant effect on these parameters. Values represent mean ± SD. *P  < 0.05 HD versus  Co; ˆP  < 0.05 HD versus  baseline; ⧫P  < 0.05 HD versus  previous.
Fig. 3. Internal carotid artery blood flow (Q̇ICA) and cerebral oxygen extraction ratio (O2ERICA) after 20, 40, 60, and 90 ml/kg hemodilution (with hematocrit values) and consequent hyperoxic ventilation (HO, beyond dotted line) in 10 anesthetized pigs (HD) and at corresponding time points in 5 control animals (Co). Q̇ICAincreased after the first hemodilution step, O2ERICAafter the third hemodilution step. Hyperoxia had no significant effect on these parameters. Values represent mean ± SD. *P 
	< 0.05 HD versus 
	Co; ˆP 
	< 0.05 HD versus 
	baseline; ⧫P 
	< 0.05 HD versus 
	previous.
Fig. 3. Internal carotid artery blood flow (Q̇ICA) and cerebral oxygen extraction ratio (O2ERICA) after 20, 40, 60, and 90 ml/kg hemodilution (with hematocrit values) and consequent hyperoxic ventilation (HO, beyond dotted line) in 10 anesthetized pigs (HD) and at corresponding time points in 5 control animals (Co). Q̇ICAincreased after the first hemodilution step, O2ERICAafter the third hemodilution step. Hyperoxia had no significant effect on these parameters. Values represent mean ± SD. *P  < 0.05 HD versus  Co; ˆP  < 0.05 HD versus  baseline; ⧫P  < 0.05 HD versus  previous.
×
Fig. 4. Intestinal serosal and mucosal, and cerebral cortex microvascular oxygen partial pressure (μPo2) and mesenteric and jugular venous Po2values after 20, 40, 60, and 90 ml/kg hemodilution (with hematocrit values) and consequent hyperoxic ventilation (HO, beyond dotted line) in 10 anesthetized pigs (HD) and at corresponding time points in 5 control animals (Co). Serosal μPo2decreased significantly after the second hemodilution step, whereas the mucosal μ Po2fell after 60 ml/kg blood exchange. Mesenteric venous Po2decreased throughout the complete hemodilution procedure. Cerebral μPo2decreased significantly after the third hemodilution step, similar to the internal jugular venous Po2. Hyperoxia increased all μPo2values and raised the venous Po2above baseline levels in the hemodilution group but had no significant effect on these parameters in the control group. Values represent mean ± SD. *P  < 0.05 HD versus  Co; ˆP  < 0.05 HD versus  baseline; ⧫P  < 0.05 HD versus  previous.
Fig. 4. Intestinal serosal and mucosal, and cerebral cortex microvascular oxygen partial pressure (μPo2) and mesenteric and jugular venous Po2values after 20, 40, 60, and 90 ml/kg hemodilution (with hematocrit values) and consequent hyperoxic ventilation (HO, beyond dotted line) in 10 anesthetized pigs (HD) and at corresponding time points in 5 control animals (Co). Serosal μPo2decreased significantly after the second hemodilution step, whereas the mucosal μ Po2fell after 60 ml/kg blood exchange. Mesenteric venous Po2decreased throughout the complete hemodilution procedure. Cerebral μPo2decreased significantly after the third hemodilution step, similar to the internal jugular venous Po2. Hyperoxia increased all μPo2values and raised the venous Po2above baseline levels in the hemodilution group but had no significant effect on these parameters in the control group. Values represent mean ± SD. *P 
	< 0.05 HD versus 
	Co; ˆP 
	< 0.05 HD versus 
	baseline; ⧫P 
	< 0.05 HD versus 
	previous.
Fig. 4. Intestinal serosal and mucosal, and cerebral cortex microvascular oxygen partial pressure (μPo2) and mesenteric and jugular venous Po2values after 20, 40, 60, and 90 ml/kg hemodilution (with hematocrit values) and consequent hyperoxic ventilation (HO, beyond dotted line) in 10 anesthetized pigs (HD) and at corresponding time points in 5 control animals (Co). Serosal μPo2decreased significantly after the second hemodilution step, whereas the mucosal μ Po2fell after 60 ml/kg blood exchange. Mesenteric venous Po2decreased throughout the complete hemodilution procedure. Cerebral μPo2decreased significantly after the third hemodilution step, similar to the internal jugular venous Po2. Hyperoxia increased all μPo2values and raised the venous Po2above baseline levels in the hemodilution group but had no significant effect on these parameters in the control group. Values represent mean ± SD. *P  < 0.05 HD versus  Co; ˆP  < 0.05 HD versus  baseline; ⧫P  < 0.05 HD versus  previous.
×
Fig. 5. (A  ) Critical levels of hemodilution for the systemic oxygen consumption (V̇o2), calculated for the hematocrit. The critical values were determined for each animal separately, resulting in an average critical hematocrit of 13.7 ± 3.5%. (B  ) Critical levels of hemodilution for the mucosal microvascular oxygen partial pressure (μ Po2), calculated for the hematocrit. The critical values were determined for each animal separately, resulting in an average critical hematocrit of 11.4 ± 2.6%. (C  ) Critical levels of hemodilution for the serosal μPo2, calculated for the hematocrit. The critical values were determined for each animal separately, resulting in an average critical hematocrit of 16.9 ± 4.2%, which was significantly higher than the critical hematocrit values of the mucosal and cerebral μPo2and systemic V̇o2. (D  ) Critical levels of hemodilution for the cerebral cortex μPo2, calculated for the hematocrit. The critical values were determined for each animal separately, resulting in an average critical hematocrit of 12.1 ± 3.1%.
Fig. 5. (A 
	) Critical levels of hemodilution for the systemic oxygen consumption (V̇o2), calculated for the hematocrit. The critical values were determined for each animal separately, resulting in an average critical hematocrit of 13.7 ± 3.5%. (B 
	) Critical levels of hemodilution for the mucosal microvascular oxygen partial pressure (μ Po2), calculated for the hematocrit. The critical values were determined for each animal separately, resulting in an average critical hematocrit of 11.4 ± 2.6%. (C 
	) Critical levels of hemodilution for the serosal μPo2, calculated for the hematocrit. The critical values were determined for each animal separately, resulting in an average critical hematocrit of 16.9 ± 4.2%, which was significantly higher than the critical hematocrit values of the mucosal and cerebral μPo2and systemic V̇o2. (D 
	) Critical levels of hemodilution for the cerebral cortex μPo2, calculated for the hematocrit. The critical values were determined for each animal separately, resulting in an average critical hematocrit of 12.1 ± 3.1%.
Fig. 5. (A  ) Critical levels of hemodilution for the systemic oxygen consumption (V̇o2), calculated for the hematocrit. The critical values were determined for each animal separately, resulting in an average critical hematocrit of 13.7 ± 3.5%. (B  ) Critical levels of hemodilution for the mucosal microvascular oxygen partial pressure (μ Po2), calculated for the hematocrit. The critical values were determined for each animal separately, resulting in an average critical hematocrit of 11.4 ± 2.6%. (C  ) Critical levels of hemodilution for the serosal μPo2, calculated for the hematocrit. The critical values were determined for each animal separately, resulting in an average critical hematocrit of 16.9 ± 4.2%, which was significantly higher than the critical hematocrit values of the mucosal and cerebral μPo2and systemic V̇o2. (D  ) Critical levels of hemodilution for the cerebral cortex μPo2, calculated for the hematocrit. The critical values were determined for each animal separately, resulting in an average critical hematocrit of 12.1 ± 3.1%.
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Table 1. Hemodynamic Measurements during Isovolemic Hemodilution and Hyperoxia
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Table 1. Hemodynamic Measurements during Isovolemic Hemodilution and Hyperoxia
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Table 2. Systemic Blood Gas and Lactate Measurements during Isovolemic Hemodilution and Hyperoxia
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Table 2. Systemic Blood Gas and Lactate Measurements during Isovolemic Hemodilution and Hyperoxia
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Table 3. Regional Venous Blood Gas and Lactate Measurements during Hemodilution and Hyperoxia
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Table 3. Regional Venous Blood Gas and Lactate Measurements during Hemodilution and Hyperoxia
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