19. Deep Hypothermic Circulatory Arrest Causes Multisystem Vascular Endothelia Dysfunction and Apoptosis

William A. Cooper, Ignacio G. Duarte, Vinod H. Thourani, Masanori Nakamura, W. Morris Brown, III, John Parker Gott, Jakob Vinten-Johansen, Robert A. Guyton

Emory University School of Medicine

Atlanta, Ga.

Background: Multisystem organ failure after hypothermic circulatory arrest (HCA) may occur secondary to endothelial dysfunction and apoptosis. Hypothesis: HCA causes endothelial dysfunction and apoptosis in brain, kidney, lungs and other tissues.

Methods: Pigs on cardiopulmonary bypass were 1) cooled to 18°C, circulation arrested (60 minutes) and reperfused at 37°C for 90 minutes (HCA, n=8) or 2) time-matched normothermic controls (CPB, n=6). Endothelial function was assessed by vasorelaxation responses to endothelial-specific bradykinin (BK) or acetylcholine (ACh), and smooth muscle-specific nitroprusside.

Results: In cerebral arteries, endothelial relaxation (BK) was impaired in HCA versus CPB [maximal 55±2 percent* vs 100±6 percent]. Pulmonary artery (ACh) responses were comparable between CPB (110±3 percent*) relative to CPB (137±6). In renal arteries, endothelial responses (ACh) were impaired in HCA (71±13 percent) relative to CPB (129±14 percent). Apoptosis (DNA laddering) occurred only in duodenal tissue in HCA (78 percent*) compared to CPB (17 percent) and non-bypass controls (nine percent).

Conclusions: HCA is associated with vascular endothelial dysfunction in cerebral and renal arteries and pulmonary veins, and localized apoptosis. Vascular endothelia dysfunction may be involved in the pathophysiology of multisystem organ failure after HCA. *p<0.05.