Decreased Myogenic Reactivity in Skeletal Muscle Arterioles after Hypothermic Cardiopulmonary Bypass

Abstract

Cardiopulmonary bypass (CPB) is associated with a generalized defect in the intrinsic control of vascular smooth muscle. To determine if myogenic reactivity of skeletal muscle arterioles was altered by CPB, sheep (n= 7) were placed on hypothermic CPB (27°C) for 90 min and hearts were arrested by cold blood cardioplegia ([K+] = 25 mM) for 60 min. Arterioles (70–180 μm) were isolated from the gracilis muscle before (control) and 15 min after CPB.In vitroarteriolar responses were studied with video-microscopy. Myogenic reactivity was examined to stepwise increases in intraluminal pressure from 10 to 100 mm Hg. Mean arterial pressure was decreased from 80 ± 15 prior to CPB to 55 ± 4 mm Hg (P< 0.01) 15 min after CPB. Myogenic contraction was observed in control vessels and was markedly attenuated by the protein kinase C inhibitor staurosporine (P< 0.01). CPB decreased myogenic contraction and shifted the pressure–diameter relation upward, suggesting a decrease in the intrinsic tone (bothP< 0.05 vs control). CPB reduced contractile responses to the α1-adrenoceptor agonist phenylephrine from −43 ± 7% to −23 ± 5% (P< 0.01) and the protein kinase C activator 12-deoxyphorbol 13-isobutyrate 20-acetate (phorbol ester) from −64 ± 6% to −38 ± 16% (P< 0.01). CPB-associated decrease in myogenic reactivity of skeletal muscle arterioles is likely due to alterations in protein kinase C and/or downstream signal transduction. This may account in part for reduction in systemic vascular resistance and hypotension associated with CPB.