Regulation of pulmonary resistance during cardiopulmonary preservation.
To characterize the neural and vasoactive mediators of pulmonary vasoconstriction and determine whether the beneficial effect of isoproterenol could be mimicked by other agents that increase cyclic adenosine monophosphate, heart and lung organ blocks were harvested from calves and studied in a normothermic autoperfusion circuit. In the experimental protocol, measurements were obtained (A) after sternotomy but before autoperfusion (in vivo); (B) during stimulation of in vivo control with tert-butyl hydroperoxide (t-BuOOH), a lipid peroxide; (C) after cannulation and institution of in situ autoperfusion (innervated preparation); (D) following denervation and explanation (ex vivo); (E) during stimulation of ex vivo preparation with t-BuOOH; and (F,G) after administration of isoproterenol, aminophylline and prostaglandin E1 to the ex vivo preparation with (time G) and without (time F) stimulation using t-BuOOH. Plots of transpulmonary pressure gradient versus cardiac output were generated for each animal, and an index of pulmonary vascular resistance was obtained from the slope of the linear relationship. Blood samples were collected for measurement of thromboxane-B2, 6-keto-prostaglandin-F1 alpha, and complement activation products C3a and C5a. Pulmonary vasoconstriction occurred during in situ autoperfusion prior to denervation and increased further following denervation and ex vivo autoperfusion; vasoconstriction correlated with increased levels of circulating vasoactive mediators. The pulmonary vasoconstrictor response was greater in the denervated vascular bed compared with the innervated state. All agents reduced postexplant pulmonary vasoconstriction. We conclude that agents that increase cyclic AMP modulate the pulmonary vasoconstrictor response and thus may enhance lung preservation in the autoperfusion model as well as with other current preservation methods.
Kontos
G J
GJ
Division of Thoracic and Cardiovascular Surgery, Mayo Clinic, Rochester, Minnesota 55905.
Hashimoto
K
K
Mashburn
J P
JP
Schaff
H V
HV
D000527:Alprostadil / Q000494:pharmacology; D000628:Aminophylline / Q000494:pharmacology; D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D001784:Blood Gas Analysis; D002417:Cattle; D003167:Complement Activation; D015926:Complement C3a / Q000032:analysis; D000242:Cyclic AMP / Q000032:analysis; D003714:Denervation; D005260:Female; D006321:Heart; D016041:Heart-Lung Transplantation / Q000502:physiology*; D006439:Hemodynamics; D007545:Isoproterenol / Q000494:pharmacology; D007958:Leukocyte Count; D008168:Lung / Q000502:physiology*; D009926:Organ Preservation; D010477:Perfusion; D011651:Pulmonary Artery / Q000294:innervation / Q000502:physiology; D014655:Vascular Resistance; D014661:Vasoconstriction / Q000276:immunology
D000628:Aminophylline; D016718:Arachidonic Acid; D015926:Complement C3a; D000242:Cyclic AMP; D000527:Alprostadil; D007545:Isoproterenol