General anesthesia is accompanied by decreased efficiency of oxygen exchange. This proposal will evaluate the role of hypoxic pulmonary vasoconstriction (HPV) in determining arterial oxygenation during normal and abnormal hemodynamic conditions with and without volatile and intravenous anesthetic agents. Initial studies in rats will define a unique model for rapid and economic study of the factors influencing HPV. The effects of mixed venous oxygen tension and content, and of carbon dioxide tension, pH, and temperature will be investigated. With this basis the influence of the volatile general anesthetics halothane, isoflurane and enflurane will be examined and compared with the intravenous anesthetic agents, pentothal, ketamine and fentanyl. Subsequent studies in dogs will test further the effects of anesthetic agents when the size of the hypoxic test segment is altered. From these results predictive equations will be derived including pulmonary artery pressure, cardiac output, PA02, PV02, PVC02, pHV, CV02, temperature, and anesthetic agents. All of these factors will be further defined in terms of the four physiologic determinants: test segment size, vascular smooth muscle constriction, and conductance change of the parallel circuits in normoxic and hypoxic lung regions. Further studies will investigate the responses in dogs with atalectasis or pneumonia with and without exposure to volatile anesthetics and with and without control of mixed venous oxygen tension. Finally observations will be recorded in human subjects undergoing one lung anesthesia for thoracic surgery and in patients following cardiopulmonary bypass procedures with and without pulmonary hypertension. The responses observed in these studies will be interpretated from the results of the previous investigations of variables, and the roles of anesthesia and of pulmonary hemodynamic changes in the etiology of hypoxemia will be evaluated.

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National Institute of General Medical Sciences (NIGMS)
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University of Pennsylvania
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Marshall, B E; Chen, L; Frasch, H F et al. (1998) Improved oxygenation with prostaglandin F2alpha with and without inhaled nitric oxide in dogs. J Appl Physiol 84:1350-8
Ozaki, M; Marshall, C; Amaki, Y et al. (1998) Role of wall tension in hypoxic responses of isolated rat pulmonary arteries. Am J Physiol 275:L1069-77
O'Hara, D A; Hexem, J G; Derbyshire, G J et al. (1997) The use of a PID controller to model vecuronium pharmacokinetics and pharmacodynamics during liver transplantation. Proportional-integral-derivative. IEEE Trans Biomed Eng 44:610-9
Hanson 3rd, C W; Marshall, B E; Frasch, H F et al. (1996) Causes of hypercarbia with oxygen therapy in patients with chronic obstructive pulmonary disease. Crit Care Med 24:23-8
Marshall, C; Mamary, A J; Verhoeven, A J et al. (1996) Pulmonary artery NADPH-oxidase is activated in hypoxic pulmonary vasoconstriction. Am J Respir Cell Mol Biol 15:633-44
Marshall, B E; Marshall, C; Frasch, F et al. (1994) Role of hypoxic pulmonary vasoconstriction in pulmonary gas exchange and blood flow distribution. 1. Physiologic concepts. Intensive Care Med 20:291-7
Marshall, B E; Hanson, C W; Frasch, F et al. (1994) Role of hypoxic pulmonary vasoconstriction in pulmonary gas exchange and blood flow distribution. 2. Pathophysiology. Intensive Care Med 20:379-89
Marshall, B E; Clarke, W R; Costarino, A T et al. (1994) The dose-response relationship for hypoxic pulmonary vasoconstriction. Respir Physiol 96:231-47
Marshall, C; Marshall, B E (1992) Hypoxic pulmonary vasoconstriction is not endothelium dependent. Proc Soc Exp Biol Med 201:267-70
Cohen, P J (1992) Allopurinol administered prior to hepatic ischaemia in the rat prevents chemiluminescence following restoration of circulation. Can J Anaesth 39:1090-3

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