B. B. Chen

Pulmonary vasoregulation by cyclooxygenase metabolites and angiotensin II after hypoperfusion in conscious, pentobarbital-anesthetized, and halothane-anesthetized dogs

The authors investigated the extent to which endogenously produced metabolities of the cyclooxygenase pathway and angiotensin II modulate the pulmonary vascular response to increasing pulmonary blood flow after a period of systemic and pulmonary hypotension and hypoperfusion (defined as posthypoperfusion) in conscious, pentobarbital-anesthetized, and halothane-anesthetized dogs. The authors tested the hypothesis that vasodilator metabolites of the cyclooxygenase pathway offset the vasoconstrictor influence of angiotensin II to prevent pulmonary vasoconstriction posthypoperfusion. Baseline and posthypoperfusion pulmonary vascular pressure-cardiac index (P/Q) plots were constructed by stepwise inflation and deflation, respectively, of a hydraulic occluder implanted around the inferior vena cava to vary Q. In intact (no drug), conscious dogs, the pulmonary vascular P/Q relationship posthypoperfusion was not altered significantly compared with baseline. In contrast, after cyclooxygenase inhibition, active flow-independent pulmonary vasoconstriction (12-17%; P less than 0.01) was observed posthypoperfusion, and this response was abolished entirely by angiotensin converting-enzyme inhibition. During pentobarbital anesthesia, significant pulmonary vasoconstriction (27%; P less than 0.01) occurred posthypoperfusion in the no-drug condition. However, the magnitude of the posthypoperfusion vasoconstriction was not increased by cyclooxygenase inhibition, nor was it reduced by converting-enzyme inhibition. During halothane anesthesia, pulmonary vasoconstriction was not observed posthypoperfusion in the no-drug condition, but it was unmasked (8-13%; P less than 0.05) by cyclooxygenase inhibition and attenuated partially by converting-enzyme inhibition. These results indicate that cyclooxygenase metabolites and angiotensin II exert opposing vasodilator and vasoconstrictor effects, respectively, on the pulmonary circulation of conscious dogs posthypoperfusion. These competing mechanisms are active during halothane anesthesia but are abolished during pentobarbital anesthesia.

Hemodynamic effects and onset time of increasing doses of vecuronium in patients undergoing myocardial revascularization

Study objectives were (1) to compare the hemodynamic effects of increasing doses of vecuronium, given as a bolus during induction of anesthesia using high-dose fentanyl, in patients undergoing myocardial revascularization; and (2) to determine whether increasing the dose of vecuronium would decrease the onset time to maximal depression of twitch response. Forty patients scheduled for elective coronary artery bypass surgery were randomly assigned to four equal groups to receive either 0.1, 0.2, 0.3, or 0.4 mg/kg of vecuronium. Hemodynamic measurements and neuromuscular blockade were recorded at five time points: A, awake state; B, anesthetized state after the administration of fentanyl, 10 micrograms/kg; C, 2 minutes after vecuronium bolus; D, 5 minutes after vecuronium bolus; and E, after intubation. Increasing the dose of vecuronium from 0.1 to 0.2 mg/kg decreased the onset time from 3.8 +/- 0.3 minutes to 1.8 +/- 0.2 minutes (P less than 0.05). However, higher doses of vecuronium (0.3 or 0.4 mg/kg) did not result in further decreases in onset time. There were no significant differences in any hemodynamic parameter measured among the four groups in the anesthetized baseline state. Compared with the anesthetized state, the administration of vecuronium resulted in few alterations in hemodynamics within the groups studied. There were no changes in any hemodynamic parameter at 2 and 5 minutes following administration of 0.4 mg/kg of vecuronium. There were also no dose-related changes in any hemodynamic parameter. Thus, high doses of vecuronium of up to 0.4 mg/kg may be administered to patients with coronary artery disease with few hemodynamic changes.(ABSTRACT TRUNCATED AT 250 WORDS)

PULMONARY VASCULAR RESPONSE TO INCREASING CARDIAC INDEX FOLLOWING SYSTEMIC HYPOTENSION IS MODIFIED BY PENTOBARBITAL ANESTHESIA

We examined the effect of sodium pentobarbital (PB) anesthesia on the pulmonary vascular response to increasing cardiac index (CI) following systemic hypotension (H). The pulmonary vascular pressure gradient (pulmonary arterial-pulmonary capillary wedge pressure:AP) was measured at multiple levels of CI (ml/min/kg) during stepwise inflation and deflation of an inferior vena cava (IVC) occluder in 10 conscious dogs, and again during PB anesthesia (30 mg/kg, iv). Maximum IVC constriction decreased (p<0.01) CI (131 ± 9 to 46 ± 4 vs 120 ± 8 to 39 ± 4) and systemic arterial pressure (113 ± 2 to 51 ± 2 mmHg vs 94 ± 4 to 47 ± 2 mmHg) in conscious and PB dogs, respectively. Following 15 rain of H, CI was gradually increased by deflation of the IVC occluder. Compared to values obtained during inflation of the IVC occluder, AP was not significantly changed at any level of CI following H in conscious dogs. For example, δP was 6.0 ± 0.5 mmHg before and 6.0 ± 0.6 mmHg after H at CI = 60, and 11.7 ± 0.7 mmHg before and 11.8 ± 0.8 mmHg after H at CI - 120. In contrast, pulmonary vasoconstriction was observed following H during PB, i.e. ΔP was increased (p<0.01) 24 ± 5% from 6.1 ± 0.4 mmHg at CI - 60, and 30 ± 7% from 10.5 ± 0.6 mmHg at CI = 120. Thus, pulmonary vascular regulation following H is altered by PB anesthesia.

NEURAL REGULATION OF THE PULMONARY CIRCULATION FOLLOWING SYSTEMIC HYPOTENSION IN CONSCIOUS DOGS

To investigate autonomic nervous system (ANS) regulation of the pulmonary vascular response to increasing cardiac index (CI:ml/min/kg) following systemic hypotension (H), the pulmonary vascular pressure gradient (pulmonary arterial-pulmonary capillary wedge pressure: ΔP) was measured at multiple levels of CI during stepwise inflation and deflation of an inferior vena cava (IVC) occluder. In intact dogs, maximum IVC constriction decreased (p<0.01) CI from 139±9 to 46±3, and systemic arterial pressure from 108±2 to 55±3 mmHg. Following 15 minutes of H, CI was gradually increased by deflation of the IVC occluder. Surprisingly, ΔP was not significantly changed at any level of CI following H in intact dogs or after cholinergic block (atropine 0.1 mg/kg). In contrast, β adrenergic block (propranolol 1 mg/kg) increased ΔP at every level of CI following H, e.g. at CI = 100, ΔP was increased (p<0.01) 16±2% from 10.2±0.5 mmHg. Pulmonary vasoconstriction following H was not observed during total autonomic ganglionic block (hexamethoniura 30 mg/kg), i.e. AP at CI - 100 was slightly decreased (p<0.05) 6±2% from 9.7±0.8 mmHg following H. These results suggest that the pulmonary circulation is actively modulated by the ANS following H. ANS-mediated vasodilator and vasoconstrictor influences appear to offset one another in the intact and cholinergic blocked conscious dog.