Hypothermic circulatory arrest causes multisystem vascular endothelial dysfunction and apoptosis

doi:10.1016/S0003-4975(99)01524-6

The Annals of Thoracic Surgery

Volume 69, Issue 3, March 2000, Pages 696-702

Presented at the Forty-Fifth Annual Meeting of the Southern Thoracic Surgical Association, Orlando, FL, Nov 12–14, 1998.

https://doi.org/10.1016/S0003-4975(99)01524-6 Get rights and content

Abstract

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°C, and had their circulation arrested (60 minutes) and reperfused at 37°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.

Section snippets

Material and methods

Animals were cared for in accordance with the guidelines of the Emory University Institutional Animal Care and Use Committee and the “Guidelines for the Care and Use of Laboratory Animals” published by the National Institutes of Health (NIH publication 85-23, revised 1985).

Pigs (17 to 25 kg) were premedicated with intramuscular ketamine (30 mg/kg), xylazine (20 mg/kg), and diazepam (0.2 mg/kg), and anesthetized with sodium thiopental 20 mg/kg intravenously. Subsequent dosing of 1 to 2 mg/kg of

In vivo transcranial cerebrovascular responses

Average body temperature during the circulatory arrest period was 17.5 ± 3.9°C (range 13.0°C to 22.1°C). Average time to rewarm to 37°C was 97.5 ± 13.5 minutes.

Comment

The activation of inflammatory processes associated with both CPB and systemic circulatory arrest contribute to endothelial dysfunction in a number of organs. In the present study, in vivo endothelial dysfunction in the transcranial circulation was not observed after either normothermic CPB or DHCA. However, endothelial dysfunction was observed in selected cerebral microvessels in the group exposed to CPB without circulatory arrest, while no endothelial dysfunction was observed in the DHCA

Acknowledgements

We wish to thank the Carlyle Fraser Heart Center for their continued support of the research efforts of the laboratory. We appreciate the technical assistance of Steve Shearer, Sara L. Katzmark, Jill R. Robinson, and L. Susan Schmarkey.

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Original ArticlesHypothermic circulatory arrest causes multisystem vascular endothelial dysfunction and apoptosis

Abstract

Section snippets

Material and methods

In vivo transcranial cerebrovascular responses

Comment

Acknowledgements

Ann Thorac Surg

Ann Thorac Surg

Ann Thorac Surg

Ann Thorac Surg

J Thorac Cardiovasc Surg

Ann Thorac Surg

J Thorac Cardiovasc Surg

J Thorac Cardiovasc Surg

J Thorac Cardiovasc Surg

Original Articles
Hypothermic circulatory arrest causes multisystem vascular endothelial dysfunction and apoptosis