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Meeting Abstracts  |   December 1998
Preservation of Hypoxic Pulmonary Vasoconstriction during Sevoflurane and Desflurane Anesthesia Compared to the Conscious State in Chronically Instrumented Dogs 
Author Notes
  • (Lesitsky) Resident, Division of Anesthesiology and Critical Care Medicine.
  • (Davis) Staff Physician, Pediatric Intensive Care Unit.
  • (Murray) Carl E. Wasmuth Endowed Chair and Director, Center for Anesthesiology Research.
Article Information
Meeting Abstracts   |   December 1998
Preservation of Hypoxic Pulmonary Vasoconstriction during Sevoflurane and Desflurane Anesthesia Compared to the Conscious State in Chronically Instrumented Dogs 
Anesthesiology 12 1998, Vol.89, 1501-1508. doi:
Anesthesiology 12 1998, Vol.89, 1501-1508. doi:
HYPOXIC pulmonary vasoconstriction (HPV) is a homeostatic mechanism whereby a decrease in alveolar PO2leads to constriction of adjacent arterioles and a subsequent diversion of blood flow to better oxygenated regions of the lung. [1] General anesthesia or surgical manipulation may result in an attenuation of HPV, leading to impaired gas exchange and arterial hypoxemia. It is widely accepted that volatile anesthetics attenuate HPV, [2-7] although there are reports in the literature that are not consistent with this concept. [8-10] Sevoflurane and desflurane are volatile anesthetics being used with increasing frequency because of their cardiac stability, rapid induction, and speed of emergence. Sevoflurane and desflurane have been shown to inhibit HPV in isolated perfused lung preparations. [11,12] Our goal was to assess the effects of sevoflurane and desflurane anesthesia on the magnitude of HPV in intact dogs that had been chronically instrumented to measure the left pulmonary vascular pressure-flow (LPQ) relationship. This experimental model has several important advantages. The chronic instrumentation allowed us to avoid the effects of acute surgical trauma and to assess the HPV response in the same animal in the conscious state and during sevoflurane and desflurane anesthesia. It also obviated the need for background anesthetics, which are known to modify neural, [13,14] humoral, [15,16] and local [17,18] mechanisms of pulmonary vasoregulation. Moreover, the use of LPQ plots to assess the effects of these volatile anesthetics on HPV avoids the limitations inherent in the interpretation of single-point calculations of pulmonary vascular resistance. [19] This is particularly important because the magnitude of HPV depends on the absolute level of pulmonary blood flow. [4] Based on our recent finding that isoflurane anesthesia attenuates the magnitude of HPV, [4] we tested the hypothesis that this effect is a general characteristics of inhalational anesthetics. Surprisingly our results indicate that HPV is preserved during sevoflurane and desflurane anesthesia compared with the response measured in the conscious state.
Materials and Methods
All surgical procedures and experimental protocols were approved by the Institutional Animal Care and Use Committee.
Surgery for Chronic Instrumentation
Seven conditioned, male mongrel dogs (weight, 22-27 kg) were premedicated with morphine sulfate (10 mg, intramuscular) and anesthetized with intravenous pentobarbital sodium (20 mg/kg) and fentanyl citrate (15 [micro sign]g/kg). After tracheal intubation, the lungs were mechanically ventilated. Anesthesia was maintained with halothane ([tilde operator] 1.2% end-tidal). With the use of sterile surgical technique, a left lateral thoracotomy was performed via the fifth intercostal space. The pericardium was incised ventral to the phrenic nerve. Heparin-filled Tygon catheters (1.02 mm ID, Norton, Akron, OH) were inserted into the descending thoracic aorta, left and right atrium, and main pulmonary artery and were secured with purse-string sutures. After careful dissection and isolation, a hydraulic occluder (18 mm ID, In Vivo Metric, Healdsburg, CA) was loosely positioned around the right main pulmonary artery, and an electromagnetic flow probe (10 mm ID, Zepeda, Seattle, WA) was placed around the left main pulmonary artery. After loose apposition of the pericardial edges, the free ends of the catheters, occluder, and flow probe were threaded through the chest wall and were tunneled subcutaneously to a final position between the scapulae. A chest tube placed in the left thorax before closure was removed 1 day after surgery. Morphine sulfate (10 mg, intramuscular) was administered after surgery for pain as required. Intravenous ampicillin (1 g), cefazolin (1 g), and gentamicin (80 mg) were administered during surgery and on a daily basis for 10 days after surgery. The dogs were allowed to recover for at least 2 weeks before experimentation.
Experimental Measurements
Vascular pressures were measured by attaching the fluid-filled catheters to strain-gauge manometers (Isotec[trade mark sign], Quest Medical, Allen, TX). Vascular pressures were referenced to atmospheric pressure with the transducers positioned at midchest at the level of the spine with the dogs in the right lateral position. Heart rate (HR) was calculated from the phasic systemic arterial pressure (SAP) trace. Left pulmonary blood flow (LQ) was measured by connecting the flow probe to an electromagnetic flowmeter (SWF-5RD, Zepeda). The flow probe was calibrated in vivo on a weekly basis via the thermal dilution technique. This was achieved by acutely inserting a 7-French, balloon-tipped thermal dilution catheter into the pulmonary artery through a percutaneous jugular puncture after topical anesthesia (lidocaine spray). The catheter was positioned 2-3 cm beyond the pulmonic valve. The implanted perivascular hydraulic occluder was then inflated to occlude the right main pulmonary artery completely, which directed total pulmonary blood flow through the left pulmonary artery (and flow probe). LQ was then measured by thermal dilution (HEMOPRO2, Spectramed, Oxnard, CA) with multiple 10-ml sterile injectates of 5% dextrose in water. Values for LQ were referenced to body weight (ml [middle dot] min-1[middle dot] kg-1). The aortic and pulmonary artery catheters were used to obtain blood samples to measure systemic arterial and mixed venous blood gases, respectively. Systemic arterial and mixed venous pH, carbon dioxide tension (PCO(2)), and oxygen tension (PO(2)) were measured with an ABL-600 (Radiometer, Copenhagen, Denmark). Oxyhemoglobin saturation (SO(2)) was measured with a Hemoximeter OSM-3 (Radiometer).
Experimental Protocols
All experiments were performed on healthy, chronically instrumented dogs lying on their right side in a quiet laboratory environment. Conscious dogs were not sedated, and anesthetized dogs were not paralyzed. LPQ plots were used to assess the effects of hypoxia, sevoflurane, and desflurane on the pulmonary circulation. LPQ plots were constructed by continuously measuring the pulmonary vascular pressure gradient (pulmonary arterial pressure-left atrial pressure [PAP-LAP]) and LQ during gradual ([tilde operator] 1 min) inflation of the hydraulic occluder implanted around the right main pulmonary artery. This technique is highly reproducible and has little or no effect on systemic hemodynamics, blood gases, or the zonal condition of the lung. [20] 
A baseline LPQ plot was obtained during normoxia in each conscious dog (n = 7). A conical face mask was then placed over the dog's snout. Room air was administered via the mask using a semi-closed circulation system, and after 10 min, a second normoxia LPQ plot with the face mask was obtained. The delivered room air was then blended with gases from sources consisting of either 100% nitrogen, 100% oxygen, or 100% carbon dioxide. The gas flows were adjusted to achieve a gradual reduction in the fractional inspired O2tension (FiO(2)) and a consequent decrease in systemic arterial PO(2) to [tilde operator] 50 mmHg. The FIO(2) during normoxia (22-25%) was decreased to 10-13% during hypoxia, as measured by mass spectrometry (Solar 7000, Marquette Electronics, Milwaukee, WI). After the attainment of a new steady-state ([tilde operator] 10 min), a hypoxia LPQ plot was generated. Three LPQ plots were generated during hypoxia to verify the stability and reproducibility of the response.
On two separate days, this protocol was repeated in the same seven dogs during either sevoflurane or desflurane anesthesia. A baseline LPQ plot was first generated during normoxia in the conscious state. After a subanesthetic dose (4 mg/kg) of intravenous thiopental to minimize excitatory behavior, either sevoflurane or desflurane was administered via face mask. After attaining a deep anesthetic depth, the trachea was intubated (9 mm ID), and ventilation was controlled with zero end-expiratory pressure. Fresh gas flow was set at 100 ml [middle dot] min-1[middle dot] kg-1; tidal volume was set at 15 ml/kg, and either sevoflurane (Sevotec 3, Ohmeda, Austell, GA) or desflurane (Tec 6, Ohmeda) was delivered via a vaporizer. Body temperature was monitored and maintained between 38-39 [degree sign]C with a warming blanket during the course of the experiment. Systemic arterial blood gases were matched to values measured in the conscious state by supplying supplemental O2and by adjusting respiratory rate. Inspiratory and end-tidal PO(2), PCO(2), sevoflurane concentration, and desflurane concentration were monitored continuously at the adapter end of the endotracheal tube (Solar 7000). Both anesthetics were allowed to equilibrate for 1 h to achieve steady-state end-tidal concentrations of [tilde operator] 3.5% for sevoflurane and 10.5% for desflurane, which represents [tilde operator] 1.5 minimum alveolar concentration (MAC) for these anesthetics in dogs. [21] At this time, serum levels of thiopental are negligible. [22] A second LPQ plot was generated during normoxia in the sevoflurane- or desflurane-anesthetized states. The hypoxic gas mixture was then administered via the endotracheal tube as described above. Once a steady-state ([tilde operator] 10 min) was achieved with systemic arterial P (O)(2)[tilde operator] 50 mmHg, an LPQ plot was generated during the hypoxic anesthetized state. Once again, three LPQ plots were generated during hypoxia to verify the stability and reproducibility of the response.
Data Analysis
Phasic and mean vascular pressures and LQ were continuously displayed on an eight-channel strip-chart recorder (2800, Gouid, Eastlake, OH). Mean values for LQ and vascular pressures were obtained using passive electronic filters with a 2-s time constant and were measured at end-expiration. Vascular pressures were referenced to atmospheric pressure before and after each LPQ plot. The analog pressure and LQ signals were digitally converted and multiplexed (Medical Systems, PCM-8, Greenvale, NY) for later playback and analysis. The LPQ relationship was linear by inspection over the empirically measured range of LQ. Therefore, linear regression analysis was used to calculate the slope and intercept for PAP-LAP (or PAP-0 if LAP <or= to 0 mmHg) as a function of LQ in each individual experiment. The correlation coefficient for each protocol averaged 0.98 or higher. Multivariate analysis of variance in the form of Hotelling's T2was used to assess the effects of hypoxia, sevoflurane, and desflurane on the baseline LPQ relationship. [23] Two-way analysis of variance (ANOVA) was used to assess the effects of the anesthetics on steady-state hemodynamics and blood gases and the magnitude of HPV. One-way ANOVA was used to assess the effects of LQ on the magnitude of HPV. All values are presented as mean +/− SEM.
Results
In conscious dogs, breathing room air via the face mask had no effect on the baseline normoxic LPQ relationship (Figure 1A). During hypoxia there was a leftward shift (P < 0.01) in the LPQ relationship, indicating HPV. The magnitude of the HPV response was dependent (P < 0.01) on the value of LQ (Figure 1B). The regression parameters for the LPQ relationship during normoxia and hypoxia are summarized in Table 1.
Table 1. Regression Parameters for Left Pulmonary Vascular Pressure-Flow Plots
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Table 1. Regression Parameters for Left Pulmonary Vascular Pressure-Flow Plots
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Figure 1. (A) Composite left pulmonary vascular pressure-flow (LPQ) plots in seven dogs in the conscious state during normoxia, during normoxia with mask, and during hypoxia. Breathing room air through the face mask had no effect on the LPQ relationship. Compared with normoxia, hypoxia resulted in a leftward shift (*P < 0.01) in the LPQ relationship indicating pulmonary vasoconstriction. (B) Composite hypoxic pulmonary vasoconstriction (HPV) response (increase in PAP-LAP from normoxia to hypoxia) as a function of left pulmonary flow in seven conscious dogs. The magnitude of HPV was flow-dependent (*P < 0.01).
Figure 1. (A) Composite left pulmonary vascular pressure-flow (LPQ) plots in seven dogs in the conscious state during normoxia, during normoxia with mask, and during hypoxia. Breathing room air through the face mask had no effect on the LPQ relationship. Compared with normoxia, hypoxia resulted in a leftward shift (*P < 0.01) in the LPQ relationship indicating pulmonary vasoconstriction. (B) Composite hypoxic pulmonary vasoconstriction (HPV) response (increase in PAP-LAP from normoxia to hypoxia) as a function of left pulmonary flow in seven conscious dogs. The magnitude of HPV was flow-dependent (*P < 0.01).
Figure 1. (A) Composite left pulmonary vascular pressure-flow (LPQ) plots in seven dogs in the conscious state during normoxia, during normoxia with mask, and during hypoxia. Breathing room air through the face mask had no effect on the LPQ relationship. Compared with normoxia, hypoxia resulted in a leftward shift (*P < 0.01) in the LPQ relationship indicating pulmonary vasoconstriction. (B) Composite hypoxic pulmonary vasoconstriction (HPV) response (increase in PAP-LAP from normoxia to hypoxia) as a function of left pulmonary flow in seven conscious dogs. The magnitude of HPV was flow-dependent (*P < 0.01).
×
The LPQ relationships during sevoflurane and desflurane anesthesia under normoxic conditions were not different from the baseline LPQ relationship during normoxia in the conscious state (Figure 2). During sevoflurane anesthesia, hypoxia caused a leftward shift (P < 0.01) in the LPQ relationship, indicating pulmonary vasoconstriction (Figure 3A). The HPV response during sevoflurane anesthesia was also dependent (P < 0.01) on LQ (Figure 3B). The magnitude of the HPV response during sevoflurane anesthesia was not significantly different from that measured in the conscious state (Figure 4).
Figure 2. Composite LPQ plots in the same seven dogs during normoxia in the conscious state, during sevoflurane anesthesia, and during desflurane anesthesia. Neither anesthetic had an effect on the LPQ relationship during normoxia.
Figure 2. Composite LPQ plots in the same seven dogs during normoxia in the conscious state, during sevoflurane anesthesia, and during desflurane anesthesia. Neither anesthetic had an effect on the LPQ relationship during normoxia.
Figure 2. Composite LPQ plots in the same seven dogs during normoxia in the conscious state, during sevoflurane anesthesia, and during desflurane anesthesia. Neither anesthetic had an effect on the LPQ relationship during normoxia.
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Figure 3. (A) Composite LPQ plots in seven dogs in the conscious state during normoxia, normoxia with sevoflurane, and hypoxia with sevoflurane. During sevoflurane anesthesia, hypoxia resulted in a leftward shift (*P < 0.01) in the LPQ relationship indicating pulmonary vasoconstriction. (B) Composite HPV response as a function of left pulmonary flow in seven dogs during sevoflurane anesthesia. The magnitude of HPV was flow-dependent (*P < 0.01).
Figure 3. (A) Composite LPQ plots in seven dogs in the conscious state during normoxia, normoxia with sevoflurane, and hypoxia with sevoflurane. During sevoflurane anesthesia, hypoxia resulted in a leftward shift (*P < 0.01) in the LPQ relationship indicating pulmonary vasoconstriction. (B) Composite HPV response as a function of left pulmonary flow in seven dogs during sevoflurane anesthesia. The magnitude of HPV was flow-dependent (*P < 0.01).
Figure 3. (A) Composite LPQ plots in seven dogs in the conscious state during normoxia, normoxia with sevoflurane, and hypoxia with sevoflurane. During sevoflurane anesthesia, hypoxia resulted in a leftward shift (*P < 0.01) in the LPQ relationship indicating pulmonary vasoconstriction. (B) Composite HPV response as a function of left pulmonary flow in seven dogs during sevoflurane anesthesia. The magnitude of HPV was flow-dependent (*P < 0.01).
×
Figure 4. Composite HPV responses as a function of left pulmonary flow in the same seven chronically instrumented dogs in the conscious state and during sevoflurane and desflurane anesthesia. Neither anesthetic had an effect on the magnitude of HPV compared with the response measured in the conscious state.
Figure 4. Composite HPV responses as a function of left pulmonary flow in the same seven chronically instrumented dogs in the conscious state and during sevoflurane and desflurane anesthesia. Neither anesthetic had an effect on the magnitude of HPV compared with the response measured in the conscious state.
Figure 4. Composite HPV responses as a function of left pulmonary flow in the same seven chronically instrumented dogs in the conscious state and during sevoflurane and desflurane anesthesia. Neither anesthetic had an effect on the magnitude of HPV compared with the response measured in the conscious state.
×
During desflurane anesthesia, hypoxia again caused a leftward shift (P < 0.01) in the LPQ relationship, indicating pulmonary vasoconstriction (Figure 5A). The HPV response during desflurane was dependent (P < 0.01) on LQ (Figure 5B) and was not different from that measured in the conscious state (Figure 4).
Figure 5. (A) Composite LPQ plots in seven dogs in the conscious state during normoxia, normoxia with desflurane, and hypoxia with desflurane. During desflurane anesthesia, hypoxia resulted in a leftward shift (*P < 0.01) in the LPQ relationship indicating pulmonary vasoconstriction. (B) Composite HPV response as a function of left pulmonary flow in seven dogs during desflurane anesthesia. The magnitude of HPV was flow-dependent (*P < 0.01).
Figure 5. (A) Composite LPQ plots in seven dogs in the conscious state during normoxia, normoxia with desflurane, and hypoxia with desflurane. During desflurane anesthesia, hypoxia resulted in a leftward shift (*P < 0.01) in the LPQ relationship indicating pulmonary vasoconstriction. (B) Composite HPV response as a function of left pulmonary flow in seven dogs during desflurane anesthesia. The magnitude of HPV was flow-dependent (*P < 0.01).
Figure 5. (A) Composite LPQ plots in seven dogs in the conscious state during normoxia, normoxia with desflurane, and hypoxia with desflurane. During desflurane anesthesia, hypoxia resulted in a leftward shift (*P < 0.01) in the LPQ relationship indicating pulmonary vasoconstriction. (B) Composite HPV response as a function of left pulmonary flow in seven dogs during desflurane anesthesia. The magnitude of HPV was flow-dependent (*P < 0.01).
×
Steady-state hemodynamics and blood gases are summarized in Table 2and Table 3, respectively. Hypoxia increased PAP in all conditions. Sevoflurane and desflurane decreased SAP and LQ and increased HR. Systemic arterial and mixed venous blood gases were similar during normoxia in all three conditions. The hypoxic gas mixture was titrated to decrease systemic arterial PO(2) to 50 +/− 1 mmHg in all three conditions.
Table 2. Steady-state Hemodynamics
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Table 2. Steady-state Hemodynamics
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Table 3. Steady-state Blood Gases
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Table 3. Steady-state Blood Gases
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Discussion
There are two new findings in this study. First, the magnitude of HPV is preserved during sevoflurane and desflurane anesthesia when compared with the response measured in the same animal in the conscious state. Second, the magnitude of HPV is dependent on the level of LQ in the conscious, sevoflurane-anesthetized and desflurane-anesthetized states.
Previous studies assessing the effects of sevoflurane and desflurane have observed an attenuation of the HPV response. [11,12] These previous studies used isolated rabbit lungs perfused at constant flow (30 ml [middle dot] min-1[middle dot] kg-1). [11,12] Thus, differences in species and level of pulmonary blood flow could account for the differential effects of the anesthetics on the HPV response in this study compared with these previous studies. In addition, possible confounding influences in those previous experiments, including acute surgical trauma and denervation, artificial nonpulsatile blood flow, presence of background anesthetics, application of PEEP, and lack of a conscious control, could explain the different findings. Acute experimental preparations may also result in the increased production of cyclooxygenase metabolites secondary to surgical manipulation and trauma. [24] Our experimental model avoids these potential confounding influences and allowed us to compare the magnitude of the HPV response in the same animal in the conscious and anesthetized states. Moreover, we compared the magnitude of the HPV response for a range of pulmonary blood flows. Because the magnitude of HPV depends on pulmonary blood flow, the flow-dependent nature of HPV should be considered when assessing the effects of physiologic or pharmacologic interventions on this response.
The magnitude of the HPV response is primarily determined by the alveolar PO(2)[25,26] and, to a lesser extent, by the PO(2) of pulmonary arterial (mixed venous) blood. [27] The threshold systemic arterial PO(2) for the initiation of HPV is approximately 60 mmHg. We did not assess the HPV response at different levels of PO(2). Rather, we chose a target PO(2) of 50 mmHg to provide a significant HPV response while at the same time maintaining cardiovascular stability in these conscious dogs. Reducing PO(2) below 50 mmHg generally causes conscious dogs to become agitated and excited. There were no differences in systemic arterial PO(2) or mixed venous PO(2) during normoxia or hypoxia among the three experimental conditions. Thus, the hypoxic stimulus was the same in all three conditions. We did observe a mild respiratory alkalosis during hypoxia in the conscious state. Although alkalosis can lead to an attenuation of the HPV response, [28,29] the degree of alkalosis was mild, and there were no significant differences in systemic arterial PCO(2) during hypoxia among the three conditions.
We did not assess a dose-response relationship for either sevoflurane or desflurane anesthesia. It is difficult to assess the effects of low-dose anesthesia in our experimental model because we do not use background anesthetics or muscle relaxants. An anesthetic concentration of 1.5 MAC allowed us to adequately control ventilation and to match blood gas values to the conscious state. Higher concentrations of anesthesia would likely have caused larger decreases in cardiac output and SAP. Thus, we used concentrations of sevoflurane and desflurane that were clinically relevant and maintained hemodynamic stability.
As expected, both anesthetics decreased baseline LQ and the peak increase in LQ during right pulmonary artery occlusion. This reflects the negative inotropic effect of the anesthetics and the associated decrease in cardiac output. As a result, the HPV response was assessed for a smaller range of LQ during anesthesia. Because of the technique to generate LPQ plots, we were not able to assess the HPV response at values of LQ below baseline in the conscious or anesthetized states. The technique that we used to induce hypoxia resulted in systemic hypoxemia, so we do not know whether we can extrapolate these results to the setting of regional hypoxia without systemic hypoxemia. Finally, both anesthetics decreased SAP. The concomitant increase in HR likely reflects an increase in sympathetic nervous system activity. However, this appeared to have no effect on the baseline LPQ relationship during normoxia in anesthetized dogs compared with the conscious state.
In summary, neither sevoflurane nor desflurane anesthesia altered the baseline LPQ relationship during normoxia. The magnitude of the HPV response was dependent on the level of pulmonary blood flow in the conscious and anesthetized states. In addition, when compared to the conscious state, the magnitude of HPV was preserved during sevoflurane and desflurane anesthesia. Thus, attenuation of HPV is not a general characteristic of all inhalational anesthetics.
The authors thank Ronnie Sanders and Cassandra Talerico for outstanding work in preparing this manuscript. The authors also are grateful for the excellent technical support provided by Steve Schomis Pantelis Konstantinopoulos, and Mike Trentanelli.
REFERENCES
Von Euler US, Liljestrand G: Observations on the pulmonary arterial blood pressure in the cat. Acta Physiol Scand 1946; 12:301-20
Pavlin EG, Su JY: Cardiopulmonary pharmacology,Anesthesia. Edited by Miller RD. New York, Churchill Livingstone, 1990, pp 105-134
Eisenkraft JB: Effects of anaesthetics on the pulmonary circulation. Br J Anaesth 1990; 65:63-78
Lennon PF, Murray PA: Attenuated hypoxic pulmonary vasoconstriction during isoflurane anesthesia is abolished by cyclooxygenase inhibition. Anesthesiology 1996; 84:404-14
Benumof JL, Wahrenbrock EA: Local effects of anesthetics on regional hypoxic pulmonary vasoconstriction. Anesthesiology 1975; 43:525-32
Mathers J, Benumof JL, Wahrenbrock EA: General anesthetics and regional hypoxic pulmonary vasoconstriction. Anesthesiology 1977; 46:111-4
Marshall C, Lindgren L, Marshall BE: Effects of halothane, enflurane, and isoflurane on hypoxic pulmonary vasoconstriction in rat lungs in vitro. Anesthesiology 1984; 60:304-8
Rogers SN, Benumof JL: Halothane and isoflurane do not decrease PaO2during one-lung ventilation in intravenously anesthetized patients. Anesth Analg 1985; 64:946-54
Carlsson AJ, Bindslev L, Hedenstierna G: Hypoxia-induced pulmonary vasoconstriction in the human lung. Anesthesiology 1987; 66:312-6
Rees DI, Gaines GY: One-lung anesthesia-A comparison of pulmonary gas exchange during anesthesia with ketamine or enflurane. Anesth Analg 1984; 63:521-5
Ishibe Y, Gui X, Uno H, Shiokawa Y, Umeda T, Suekane K: Effect of sevoflurane on hypoxic pulmonary vasoconstriction in the perfused rabbit lung. Anesthesiology 1993; 79:1348-53
Loer SA, Scheeren TW, Tarnow J: Desflurane inhibits hypoxic pulmonary vasonconstriction in isolated rabbit lungs. Anesthesiology 1995; 83:552-6
Chen BB, Nyhan DP, Fehr DM, Murray PA: Halothane anesthesia abolishes pulmonary vascular responses to neural antagonists. Am J Physiol 1992; 262:H117-22
Lennon PF, Murray PA: Isoflurane and the pulmonary vascular pressure-flow relation at baseline and during sympathetic [small alpha, Greek]- and [small beta, Greek]-adrenoreceptor activation in chronically instrumented dogs. Anesthesiology 1995; 82:723-33
Nyhan DP, Chen BB, Fehr DM, Rock P, Murray PA: Anesthesia alters pulmonary vasoregulation by angiotensin II and captopril. J Appl Physiol 1992; 72:636-42
Trempy GA, Nyhan DP, Murray PA: Pulmonary vasoregulation by arginine vasopressin in conscious, halothane-anesthetized, and pentobarbital-anesthetized dogs with increased vasomotor tone. Anesthesiology 1994; 81:632-40
Gambone LM, Fujiwara Y, Murray PA: Endothelium-dependent pulmonary vasodilation in conscious dogs is selectively attenuated during isoflurane anesthesia. Am J Physiol 1997; 41:H290-8
Seki S, Sato K, Nakayama M, Murray PA: Halothane and enflurane attenuate pulmonary vasodilation mediated by ATP-sensitive potassium channels compared to the conscious state. Anesthesiology 1997; 86:923-35
Graham R, Skoog C, Macedo W, Carter J, Oppenheimer L, Rabson J, Goldberg HS: Dopamine, dobutamine, and phentolamine effects on pulmonary vascular mechanics. J Appl Physiol 1983; 54:1277-83
Nishiwaki K, Nyhan DP, Rock P, Desai PM, Peterson WP, Pribble CG, Murray PA: N sup [small omega, Greek]-nitro-L-arginine and the pulmonary vascular pressure-flow relationship in conscious dogs. Am J Physiol 1992; 262:H1331-7
Franks NP, Lieb WR: Temperature dependence of the potency of volatile general anesthetics. Implications for in vitro experiments. Anesthesiology 1996; 84:716-20
Chen BB, Nyhan DP, Fehr DM, Goll HM, Murray PA: Halothane anesthesia causes active flow-independent pulmonary vasoconstriction. Am J Physiol 1990; 259:H74-83
Wilkinson L: Systat: The System for Statistics. Evanston, IL, Systat, 1990
Shayevitz JR, Traystman RJ, Adkinson NF, Sciuto AM, Gurtner GH: Inhalation anesthetics augment oxidant-induced pulmonary vasoconstriction: Evidence for a membrane effect. Anesthesiology 1985; 63:624-32
Hauge A: Hypoxia and pulmonary vascular resistance. The relative effects of pulmonary arterial and alveolar PO2. Acta Physiol Scand 1969; 76:121-30
Marshall C, Marshall B: Site and sensitivity for stimulation of hypoxic pulmonary vasoconstriction. J Appl Physiol 1983; 55:711-6
Benumof JL, Pirlo AF, Johanson I, Trousdale FR: Interaction of PvO2with PaO2on hypoxic pulmonary vasoconstriction. J Appl Physiol 1981; 51:871-4
Brimioulle S, Lejeune P, Vachiery JL, Leeman M, Melot C, Naeije R: Effects of acidosis and alkalosis on hypoxic pulmonary vasoconstriction in dogs. Am J Physiol 1990; 258:H347-53
Loeppky JA, Scotto P, Riedel CE, Roach RC, Chick TW: Effects of acid-base status on acute hypoxic pulmonary vasoconstriction and gas exchange. J Appl Physiol 1992; 72:1787-97
Figure 1. (A) Composite left pulmonary vascular pressure-flow (LPQ) plots in seven dogs in the conscious state during normoxia, during normoxia with mask, and during hypoxia. Breathing room air through the face mask had no effect on the LPQ relationship. Compared with normoxia, hypoxia resulted in a leftward shift (*P < 0.01) in the LPQ relationship indicating pulmonary vasoconstriction. (B) Composite hypoxic pulmonary vasoconstriction (HPV) response (increase in PAP-LAP from normoxia to hypoxia) as a function of left pulmonary flow in seven conscious dogs. The magnitude of HPV was flow-dependent (*P < 0.01).
Figure 1. (A) Composite left pulmonary vascular pressure-flow (LPQ) plots in seven dogs in the conscious state during normoxia, during normoxia with mask, and during hypoxia. Breathing room air through the face mask had no effect on the LPQ relationship. Compared with normoxia, hypoxia resulted in a leftward shift (*P < 0.01) in the LPQ relationship indicating pulmonary vasoconstriction. (B) Composite hypoxic pulmonary vasoconstriction (HPV) response (increase in PAP-LAP from normoxia to hypoxia) as a function of left pulmonary flow in seven conscious dogs. The magnitude of HPV was flow-dependent (*P < 0.01).
Figure 1. (A) Composite left pulmonary vascular pressure-flow (LPQ) plots in seven dogs in the conscious state during normoxia, during normoxia with mask, and during hypoxia. Breathing room air through the face mask had no effect on the LPQ relationship. Compared with normoxia, hypoxia resulted in a leftward shift (*P < 0.01) in the LPQ relationship indicating pulmonary vasoconstriction. (B) Composite hypoxic pulmonary vasoconstriction (HPV) response (increase in PAP-LAP from normoxia to hypoxia) as a function of left pulmonary flow in seven conscious dogs. The magnitude of HPV was flow-dependent (*P < 0.01).
×
Figure 2. Composite LPQ plots in the same seven dogs during normoxia in the conscious state, during sevoflurane anesthesia, and during desflurane anesthesia. Neither anesthetic had an effect on the LPQ relationship during normoxia.
Figure 2. Composite LPQ plots in the same seven dogs during normoxia in the conscious state, during sevoflurane anesthesia, and during desflurane anesthesia. Neither anesthetic had an effect on the LPQ relationship during normoxia.
Figure 2. Composite LPQ plots in the same seven dogs during normoxia in the conscious state, during sevoflurane anesthesia, and during desflurane anesthesia. Neither anesthetic had an effect on the LPQ relationship during normoxia.
×
Figure 3. (A) Composite LPQ plots in seven dogs in the conscious state during normoxia, normoxia with sevoflurane, and hypoxia with sevoflurane. During sevoflurane anesthesia, hypoxia resulted in a leftward shift (*P < 0.01) in the LPQ relationship indicating pulmonary vasoconstriction. (B) Composite HPV response as a function of left pulmonary flow in seven dogs during sevoflurane anesthesia. The magnitude of HPV was flow-dependent (*P < 0.01).
Figure 3. (A) Composite LPQ plots in seven dogs in the conscious state during normoxia, normoxia with sevoflurane, and hypoxia with sevoflurane. During sevoflurane anesthesia, hypoxia resulted in a leftward shift (*P < 0.01) in the LPQ relationship indicating pulmonary vasoconstriction. (B) Composite HPV response as a function of left pulmonary flow in seven dogs during sevoflurane anesthesia. The magnitude of HPV was flow-dependent (*P < 0.01).
Figure 3. (A) Composite LPQ plots in seven dogs in the conscious state during normoxia, normoxia with sevoflurane, and hypoxia with sevoflurane. During sevoflurane anesthesia, hypoxia resulted in a leftward shift (*P < 0.01) in the LPQ relationship indicating pulmonary vasoconstriction. (B) Composite HPV response as a function of left pulmonary flow in seven dogs during sevoflurane anesthesia. The magnitude of HPV was flow-dependent (*P < 0.01).
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Figure 4. Composite HPV responses as a function of left pulmonary flow in the same seven chronically instrumented dogs in the conscious state and during sevoflurane and desflurane anesthesia. Neither anesthetic had an effect on the magnitude of HPV compared with the response measured in the conscious state.
Figure 4. Composite HPV responses as a function of left pulmonary flow in the same seven chronically instrumented dogs in the conscious state and during sevoflurane and desflurane anesthesia. Neither anesthetic had an effect on the magnitude of HPV compared with the response measured in the conscious state.
Figure 4. Composite HPV responses as a function of left pulmonary flow in the same seven chronically instrumented dogs in the conscious state and during sevoflurane and desflurane anesthesia. Neither anesthetic had an effect on the magnitude of HPV compared with the response measured in the conscious state.
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Figure 5. (A) Composite LPQ plots in seven dogs in the conscious state during normoxia, normoxia with desflurane, and hypoxia with desflurane. During desflurane anesthesia, hypoxia resulted in a leftward shift (*P < 0.01) in the LPQ relationship indicating pulmonary vasoconstriction. (B) Composite HPV response as a function of left pulmonary flow in seven dogs during desflurane anesthesia. The magnitude of HPV was flow-dependent (*P < 0.01).
Figure 5. (A) Composite LPQ plots in seven dogs in the conscious state during normoxia, normoxia with desflurane, and hypoxia with desflurane. During desflurane anesthesia, hypoxia resulted in a leftward shift (*P < 0.01) in the LPQ relationship indicating pulmonary vasoconstriction. (B) Composite HPV response as a function of left pulmonary flow in seven dogs during desflurane anesthesia. The magnitude of HPV was flow-dependent (*P < 0.01).
Figure 5. (A) Composite LPQ plots in seven dogs in the conscious state during normoxia, normoxia with desflurane, and hypoxia with desflurane. During desflurane anesthesia, hypoxia resulted in a leftward shift (*P < 0.01) in the LPQ relationship indicating pulmonary vasoconstriction. (B) Composite HPV response as a function of left pulmonary flow in seven dogs during desflurane anesthesia. The magnitude of HPV was flow-dependent (*P < 0.01).
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Table 1. Regression Parameters for Left Pulmonary Vascular Pressure-Flow Plots
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Table 1. Regression Parameters for Left Pulmonary Vascular Pressure-Flow Plots
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Table 2. Steady-state Hemodynamics
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Table 2. Steady-state Hemodynamics
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Table 3. Steady-state Blood Gases
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Table 3. Steady-state Blood Gases
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