Hypothermic circulatory arrest causes multisystem vascular endothelial dysfunction and apoptosis

Background, Multiple organ failure after deep hypothermic circulatory arres t (DHCA) may occur secondary to endothelial dysfunction and apoptosis. We s ought to determine if DHCA causes endothelial dysfunction and apoptosis in brain, kidney, lungs, and other tissues. Methods, Anesthetized pigs on cardiopulmonary bypass were: (1) cooled to 18 degrees C, and had their circulation arrested (60 minutes) and reperfused at 37 degrees C for 90 minutes (DHCA, n = 8); or (2) time-matched normother mic controls on bypass (CPB, n = 6). Endothelial function in cerebral, pulm onary, and renal vessels was assessed by vasorelaxation responses to endoth elial-specific bradykinin (BK) or acetylcholine (ACh), and smooth muscle-sp ecific nitroprusside. Results, In vivo transcranial vasorelaxation responses to ACh were similar between the two groups. In small-caliber cerebral arteries, endothelial rel axation (BK) was impaired in CPB vs DHCA (maximal 55% +/- 2% [p < 0.05] vs 100% +/- 6%). Pulmonary artery ACh responses were comparable between CPB (1 10% +/- 10%) and DHCA (83% +/- 6%), but responses in pulmonary vein were im paired in DI-ICA (109% +/- 3%, p < 0.05) relative to CPB (137% +/- 6%), In renal arteries, endothelial (ACh) responses were impaired in DHCA (71% +/- 13%) relative to CPB (129% +/- 14%), Apoptosis (DNA laddering) occurred pri marily in duodenal tissue, with a greater frequency in DHCA (56%, p < 0.05) compared with normothermic CPB (17%) and nonbypass controls (0%), Conclusions, DHCA is associated with endothelial dysfunction in cerebral mi crovessels but not in the in vivo transcranial vasculature; in addition end othelial dysfunction was noted in large-caliber renal arteries and pulmonar y veins. DHCA. is also associated with duodenal apoptosis. Vascular endothe lial dysfunction and apoptosis may be involved in the pathophysiology of mu ltisystem organ failure after DHCA, (C) 2000 by The Society of Thoracic Sur geons.