Venoarterial ECMO Impairs Myogenic Reactivity and Nitric Oxide Synthase Activity in Cerebral Arteries of Lambs

Abstract 233 Poster Session III, Monday, 5/3 (poster 119)

Previous studies in our laboratory have shown that exposure of newborn lambs to venoarterial extracorporeal membrane oxygenation (VA ECMO) alters cerebral blood flow autoregulation. We postulate that this altered vascular reactivity is mediated through changes in blood pulsatile flow patterns caused by the pumping systems used in VA ECMO. These alterations result in changes in blood flow and shear stress patterns which may affect endothelial function. To test this hypothesis, 2 groups of newborn lambs were studied: ECMO animals (n=4) exposed to 2 hrs of VA ECMO, and control animals (n=3) maintained under similar conditions for 2 hrs on the ventilator without ECMO. After the 2 hr period, animals were sacrificed and their brains were removed. Third order branches of the middle cerebral arteries (150 to 300 µm diameter) were isolated and mounted on glass cannulae in an arteriograph, and superfused with Krebs-Ringer buffer. The diameter of the vessels was monitored using a video dimension analyzer. While increase in intra luminal pressure of the arteries from 45 to 85 mmHg decreased the diameter of vessels from control animals (97.8 ± 2.5 %), the diameter was increased (108.3 ± 3.1 %) in those from animals exposed to ECMO. Decrease in the diameter of the arteries induced by exposure of the vessels to nitric oxide synthase inhibitor N^G-nitro-L-arginine methyl ester (L-NAME; 2 × 10^-4 M) for 30 min was significantly less (p< 0.05) in arteries from lambs exposed to ECMO compared to that in control animals (26 ± 4.7 % decrease in controls compared to 7.2 ± 3.2 % in ECMO). There were no significant differences between the two groups in the contractile activity of the arteries to increasing concentrations of serotonin. These results demonstrate that 2 hours of exposure of newborn lambs to non-pulsatile venoarterial ECMO results in impairment of myogenic tone and decrease in basal activity of nitric oxide synthase in cerebral arteries, and suggest that venoarterial ECMO impairs cerebral arterial endothelial function.