Selective endothelial dysfunction in conscious dogs after cardiopulmonary bypass

Abstract

It has previously been demonstrated that cardiopulmonary bypass (CPB) causes prolonged pulmonary vascular hyperreactivity (D.P. Nyhan, J.M. Redmond, A.M. Gillinov, K. Nishiwaki, and P.A. Murray. J. Appl. Physiol. 77: 1584-1590, 1994). This study investigated the effects of CPB on endothelium-dependent (acetylcholine and bradykinin) and endothelium-independent (sodium nitroprusside) pulmonary vasodilation in conscious dogs. Continuous left pulmonary vascular pressure-flow (LP-Q) plots were generated in conscious dogs before CPB and again in the same animals 3-4 days post-CPB. The dose of U-46619 used to acutely preconstrict the pulmonary circulation to similar levels pre- and post-CPB was decreased (0.13 +/- 0.01 vs. 0.10 +/- 0.01 mg.kg-1.min-1, P < 0.01) after CPB. Acetylcholine, bradykinin, and sodium nitroprusside all caused dose-dependent pulmonary vasodilation pre-CPB. The pulmonary vasodilator response to acetylcholine was completely abolished post-CPB. For example, at left pulmonary blood flow of 80 ml.kg-1.min-1 acetylcholine (10 micrograms.kg-1.min-1) resulted in 72 +/- 15% reversal (P < 0.01) of U-46619 preconstriction pre-CPB but caused no change post-CPB. However, the responses to bradykinin and sodium nitroprusside were unchanged post-CPB. The impaired pulmonary vasodilator response to acetylcholine, but not to bradykinin, suggests a selective endothelial defect post-CPB. The normal response to sodium nitroprusside indicates that cGMP-mediated vasodilation is unchanged post-CPB.

The effects of sympathetic activity induced by ice water on blood flow and brachial artery flow-mediated dilatation response in healthy volunteers

“…Brachial artery FMD measures vasodilation following an acute increase in blood flow (reactive hyperemia), typically induced by a period of circulatory occlusion [4]. It has been suggested that major surgery–and in particular, the use of cardiopulmonary bypass surgery (CBS)–triggers a systemic inflammatory response, resulting in endothelial dysfunction [5–11].…”

Inhaled prostacyclin reduces cardiopulmonary bypass–induced pulmonary endothelial dysfunction via increased cyclic adenosine monophosphate levels

“…21 ACh-related NO pathway appears to be preferentially damaged. 10,22 Indeed, Gagnon and colleagues 10 have shown in a porcine model that CPB with reperfusion of the pulmonary tree induces a decrease in endotheliumdependent relaxation mediated by muscarinic receptors, which was also demonstrated in a dog model by Zanaboni and colleagues. 22 Although ACh induces endothelium-dependent relaxation through both the NO and cAMP pathways, 23 more specific signal transduction pathways alterations may explain the lack of benefit of inhaled PGI 2 in ACh-induced dysfunction in this study.…”