Hypothermic circulatory arrest causes multisystem vascular endothelial dysfunction and apoptosis.
BACKGROUND
Multiple organ failure after deep hypothermic circulatory arrest (DHCA) may occur secondary to endothelial dysfunction and apoptosis. We sought 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 normothermic controls on bypass (CPB, n = 6). Endothelial function in cerebral, pulmonary, and renal vessels was assessed by vasorelaxation responses to endothelial-specific bradykinin (BK) or acetylcholine (ACh), and smooth muscle-specific nitroprusside.


RESULTS
In vivo transcranial vasorelaxation responses to ACh were similar between the two groups. In small-caliber cerebral arteries, endothelial relaxation (BK) was impaired in CPB vs DHCA (maximal 55% +/- 2% [p < 0.05] vs 100% +/- 6%). Pulmonary artery ACh responses were comparable between CPB (110% +/- 10%) and DHCA (83% +/- 6%), but responses in pulmonary vein were impaired in DHCA (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 primarily 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 microvessels but not in the in vivo transcranial vasculature; in addition, endothelial dysfunction was noted in large-caliber renal arteries and pulmonary veins. DHCA is also associated with duodenal apoptosis. Vascular endothelial dysfunction and apoptosis may be involved in the pathophysiology of multisystem organ failure after DHCA.
Cooper
W A
WA
Cardiothoracic Research Laboratory, Carlyle Fraser Heart Center of Crawford Long Hospital, and Emory University School of Medicine, Atlanta, Georgia 30365, USA.
Duarte
I G
IG
Thourani
V H
VH
Nakamura
M
M
Wang
N P
NP
Brown
W M
WM
Gott
J P
JP
Vinten-Johansen
J
J
Guyton
R A
RA
D000818:Animals; D017209:Apoptosis; D001921:Brain / Q000098:blood supply; D002315:Cardiopulmonary Bypass / Q000009:adverse effects; D004730:Endothelium, Vascular / Q000503:physiopathology*; D006324:Heart Arrest, Induced / Q000009:adverse effects*; D007036:Hypothermia, Induced / Q000009:adverse effects*; D007668:Kidney / Q000098:blood supply; D008168:Lung / Q000098:blood supply; D013552:Swine; D014652:Vascular Diseases / Q000209:etiology*