Altered -adrenergic and cholinergic pulmonary vascular responses after total cardiopulmonary bypass. Friedman, Menachem, Steven Y. Wang, Gregory L. Stahl, Robert G. Johnson, Frank W. Sellke. Division of Cardiothoracic Surgery, Department of Surgery, Beth Israel Hospital, Department of Anesthesiology*, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA
APStracts 2:0340A, 1995.
Cardiopulmonary bypass is often followed by pulmonary hypertension, but the effects of extracorporeal circulation on vascular reactivity remain largely unknown. In this study, the influence of total cardiopulmonary bypass (t-CPB) on -adrenergic and cholinergic receptor-mediated pulmonary microvascular responses was examined. Sheep were placed on t-CPB without ventilation. After 90 minutes, sheep were separated from t-CPB and the lungs were perfused normally for 60 minutes. Pulmonary artery infusion of ACH (muscarinic cholinergic agonist, ACH) increased pulmonary vascular resistance (PVR) significantly more and ISO ( -adrenergic agonist, ISO) decreased PVR less after, than prior to t-CPB. The response to sodium nitroprusside (SNP, guanylate cyclase activator) was similar before and after t-CPB. Relaxations (in vitro) of isolated, pressurized (20 mmHg) microvessels to ISO and ACH were markedly reduced after t- CPB. Treatment with NPC 15669 [N-(9H-)2,7,-dimethylfluorenyl-9 -methoxy)carbonyl)L-leucine] did not affect these changes in vessel reactivity, although leukocyte sequestration in the lungs was reduced with the drug. The in vitro response to forskolin (adenylate cyclase activator, FSK) and SNP was similar before and after t-CPB. Complement-activated serum caused microvessels to contract in response to ACH, but it had no effect on ISO, FSK, or SNP responses, suggesting activation of the alternate complement pathway causes a selective reduction in endothelium-dependent relaxation. We conclude that t-CPB impairs both cholinergic and -adrenergic pulmonary vascular responses, due to effects at the level of the transmembrane receptor or coupling to the second messenger systems. 

Received 9 February 1995; accepted in final form 24 July 1995.
APS Manuscript Number A153-5.
Article publication pending Journal of Applied Physiology.
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 10 August 1995.