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

Louis Mathieu Stevens, Simon Fortier, Marie Claude Aubin, Ismail El-Hamamsy, Simon Maltais, Michel Carrier, Louis P. Perrault

Research output: Contribution to journalArticlepeer-review

8 Scopus citations


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 90 min 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.

Original languageEnglish (US)
Pages (from-to)464-471
Number of pages8
JournalEuropean Journal of Cardio-Thoracic Surgery
Issue number3
StatePublished - Sep 2006


  • Antioxidant
  • Cardiopulmonary bypass
  • Coronary artery
  • Endothelial dysfunction
  • Nitric oxide
  • Superoxide dismutase
  • Tetrahydrobiopterin

ASJC Scopus subject areas

  • Surgery
  • Pulmonary and Respiratory Medicine
  • Cardiology and Cardiovascular Medicine


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