Pentobarbital augments pulmonary vasoconstrictor response to cyclooxygenase inhibition

Abstract

We utilized multipoint pulmonary vascular pressure-flow (P/Q) plots to investigate the effects of pentobarbital sodium anesthesia on regulation of the pulmonary circulation by endogenous metabolites of the cyclooxygenase pathway. Our specific objective was to characterize the effects of two chemically dissimilar inhibitors of the cyclooxygenase pathway, indomethacin and sodium meclofenamate, on the pulmonary vascular P/Q relationship measured in conscious and pentobarbital-anesthetized dogs. P/Q plots were generated by graded constriction of the thoracic inferior vena cava, which produced stepwise decreases in Q. Controlled ventilation during pentobarbital anesthesia (30 mg/kg iv) allowed the matching of systemic arterial and mixed venous blood gases to conscious values. Pentobarbital had no net effect on the base-line P/Q relationship compared with that measured in conscious dogs. Cyclooxygenase pathway inhibition with either indomethacin (5 mg/kg iv) or meclofenamate (2.5 mg/kg iv) resulted in active, flow-independent pulmonary vasoconstriction (P less than 0.01) in both conscious and pentobarbital-anesthetized dogs. However, the magnitude of the pulmonary vasoconstrictor response to indomethacin was increased (P less than 0.05) over a broad range of Q, and the pulmonary vasoconstrictor response to meclofenamate was increased (P less than 0.05) over the entire range of Q in pentobarbital-anesthetized compared with conscious dogs. Thus regulation of the base-line pulmonary vascular P/Q relationship by endogenous metabolites of the cyclooxygenase pathway in conscious dogs is altered during pentobarbital anesthesia.

Chronic intermittent hypoxia accelerates coronary microcirculatory dysfunction in insulin-resistant Goto-Kakizaki rats

“…Within the limitations of the synchrotron facilities, we have utilized pentobarbital anesthesia in our studies (16,34,37), which is known to depress myocardial contractility (21). We report here only the responses of rats after a similar period of stable anesthesia that has been shown to slightly reduce coronary and pulmonary vascular resistances in anesthetized dogs relative to conscious conditions (21,25). Therefore basal coronary flow in our anesthetized rats is likely to be slightly enhanced compared with conscious rats.…”

Selective endothelial dysfunction in conscious dogs after cardiopulmonary bypass

“…Our experimental approach has several unique features that allow our results to be attributed specifically to the effects of CPB. First, general anesthetics are recognized as modulators of vasoregulation, including pulmonary vasoregulation (5,12,22,23,25). The use of conscious animals avoids this potential confounding influence.…”

“…The LP-Q relationship was measured to determine the pulmonary vascular responses to endothelium-dependent and -independent vasodilators before and again 3-4 days after closed-chest CPB. This approach avoids the known effects of general anesthesia on neurohumoral (5,12,23,25) and local (12,19,22) mechanisms of pulmonary vasoregulation. Furthermore, measurement of continuous LP-Q plots avoids the inherent limitations of single-point calculations of pulmonary vascular resistance.…”