title: 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.
authors.affiliation: Department of Anesthesiology and Critical Care Medicine, Johns Hopkins Medical Institutions, Baltimore, Maryland 21287-8711, USA.
authors.forename: P
authors.initials: P
authors.lastname: Zanaboni
authors.forename: P A
authors.initials: PA
authors.lastname: Murray
authors.forename: B A
authors.initials: BA
authors.lastname: Simon
authors.forename: K
authors.initials: K
authors.lastname: Zehr
authors.forename: K
authors.initials: K
authors.lastname: Fleischer
authors.forename: E
authors.initials: E
authors.lastname: Tseng
authors.forename: D P
authors.initials: DP
authors.lastname: Nyhan
mesh_terms: D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001808:Blood Vessels / Q000187:drug effects; D001920:Bradykinin / Q000494:pharmacology; D001026:Coronary Artery Bypass; D004285:Dogs; D004730:Endothelium, Vascular / Q000503:physiopathology*; D008297:Male; D009599:Nitroprusside / Q000494:pharmacology; D011184:Postoperative Period; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology; D011652:Pulmonary Circulation / Q000187:drug effects; D013928:Thromboxane A2 / Q000031:analogs & derivatives / Q000494:pharmacology; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D011450:Prostaglandin Endoperoxides, Synthetic; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D009599:Nitroprusside; D013928:Thromboxane A2; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000109:Acetylcholine; D001920:Bradykinin