Anesthetic modulation of pulmonary vascular regulation

These results provide compelling evidence that general anesthesia can alter neural, hymoral, and local mechanisms of pulmonary vascular regulation. A clear strength of these studies is that we have assessed these various mechanisms of pulmonary vascular regulation in the conscious state, and then again in the same animal during general anesthesia. Our studies in chronically instrumented conscious dogs have documented that regulation of the pulmonary vascular P/Q relationship is multifactorial, and that these vascular mechanisms are interactive. These results in conscious animals serve as a database to assess the specific effects of general anesthesia on pulmonary vascular regulation. A striking finding in these studies is that different anesthetics can have differential effects on neural, humoral, and local mechanisms of pulmonary vascular regulation. Without this fundamental information, it is difficult to interpret previous experimental studies that have utilized background anesthetics. Moreover, this information is essential for the adequate clinical management of patients in the perioperative period. These in vivo studies have allowed us to identify the overall effects of general anesthetics on the integrative response of the intact organism to these diverse pulmonary vasoregulatory pathways. Our next objective is to elucidate the cellular mechanisms that mediate the effects of general anesthetics on these various mechanisms of pulmonary vasoregulation. To that end, we are now performing in vivo studies utilizing isolated pulmonary arterial rings to elucidate abnormalities in the various signal transduction pathways that could be responsible for the effects of general anesthetics. We propose to identify the loci of dysfunction in the signal transduction pathways that mediate the pulmonary vascular effects of general anesthetics on cAMP-, cGMP-, and K+ATP channel-mediated pulmonary vasodilation, as well as alpha 1- and angiotensin-mediated pulmonary vasoconstriction. These combined in vivo and in vitro approaches are complementary and can be used to delineate the effects and mechanisms of action of general anesthetics on pulmonary vasoregulation.