TITLE

Effect of tetrahydrobiopterin on selective endothelial dysfunction of epicardial porcine coronary arteries induced by cardiopulmonary bypass

AUTHOR(S)
Stevens, Louis-Mathieu; Fortier, Simon; Aubin, Marie-Claude; El-Hamamsy, Ismail; Maltais, Simon; Carrier, Michel; Perrault, Louis P.
PUB. DATE
September 2006
SOURCE
European Journal of Cardio-Thoracic Surgery;Sep2006, Vol. 30 Issue 3, p464
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
Abstract: Background: We hypothesized that cardiopulmonary bypass induces a selective alteration of the coronary arterial endothelial cell signal transduction which could be explained by a state of depletion and/or decreased activity of endogenous tetrahydrobiopterin (BH4). The aim of this study was to assess the effects of cardiopulmonary bypass and BH4 on the endothelial function of epicardial coronary arteries in a swine model of cardiopulmonary bypass. Methods: Swine underwent 90min of cardiopulmonary bypass alone (N =19) or in association with a brief cardioplegic arrest with (N =6) or without (N =5) in vivo BH4 administration, followed by a 60-min period following weaning from cardiopulmonary bypass and were compared to a control group (N =7). Endothelium-dependent relaxations of epicardial coronary artery rings were studied using standard organ chamber experiments in the presence or absence of in vitro BH4 or superoxide dismutase (SOD) and catalase. Results: Cardiopulmonary bypass caused a statistically significant reduction of endothelium-dependent relaxations to serotonin (p <0.0001), bradykinin (p <0.001), UK14304 (p <0.0001) and calcium ionophore (p <0.01) in epicardial porcine coronary arteries. In vitro and in vivo BH4 supplementation improved endothelium-dependent relaxations to serotonin and bradykinin, which were left unchanged by SOD-catalase administration. Cardiopulmonary bypass was associated with a decrease in nitric oxide availability (p =0.002) and increased oxidative stress (p <0.001), which were both restored by in vivo BH4 administration (p <0.001). Conclusion: Treatment with BH4 improves the endothelial dysfunction of porcine epicardial coronary arteries, restores nitric oxide availability and reduces the oxidative stress associated with cardiopulmonary bypass.
ACCESSION #
21920245

 

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