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Ann Thorac Surg 2005;80:1803-1811
© 2005 The Society of Thoracic Surgeons

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Original article: Cardiovascular

Hypoxia-Reoxygenation, St. Thomas Cardioplegic Solution, and Nicorandil on Endothelium-derived Hyperpolarizing Factor in Coronary Microarteries

^a Department of Surgery, The Chinese University of Hong Kong, Hong Kong
^b Department of Surgery, Providence Heart Institute, Albert Starr Academic Center, Oregon Health and Science University, Portland, Oregon; and Wuhan Heart Institute, The Central Hospital of Wuhan, Wuhan, China

Accepted for publication April 25, 2005.

^_* Address correspondence to Prof He, Department of Surgery, The Chinese University of Hong Kong, Block B, 5A, Prince of Wales Hospital, Shatin, NT, Hong Kong SAR, China (Email: gwhe{at}cuhk.edu.hk).

BACKGROUND: We investigated effects of hypoxia-reoxygenation (H-R) with and without St. Thomas solution under clinically relevant temperatures and effects of nicorandil on endothelium-derived hyperpolarizing factor (EDHF)–mediated relaxation in porcine coronary microarteries.

METHODS: In a myograph, rings of porcine microarteries (diameter 200 to 450 µm) were subjected to hypoxia (PO₂ <5 mm Hg) for 30 minutes in Krebs at 37°C, or for 60 minutes in Krebs and St. Thomas solution with or without nicorandil (0.1 µM) at 37°C or 4°C, followed by 30-minute reoxygenation. The EDHF-mediated relaxation by bradykinin (–10 to approximately –6 logM) with inhibitors of nitric oxide and prostacyclin was studied.

RESULTS: The maximal EDHF-mediated relaxation was reduced after hypoxia for 30 minutes (59.9%% ± 1.6% versus 81.2%% ± 3.5%, p < 0.05) or 60 minutes (44.4% ± 6.0% versus 82.7% ± 7.4%, p < 0.001) in Krebs or St. Thomas (28.9% ± 1.8% versus 78.1% ± 3.0%, p < 0.001) at 37°C and at 4°C (Krebs: 49.3% ± 3.0%, p < 0.001; ST: 43.1% ± 2.6%, p < 0.001) and it was less in St. Thomas solution at 37°C than at 4°C (p < 0.001). The reduced relaxation was recovered by nicorandil (Krebs at 37°C: 81.7% ± 3.4%, p < 0.001; St. Thomas at 37°C: 71.0% ± 7.9%, p <0.001; St. Thomas at 4°C: 85.3% ± 3.3%, p < 0.001).

CONCLUSIONS: We conclude that (1) H-R impairs EDHF-mediated relaxation in the coronary microarteries with more injury during prolonged H-R, and this can be partially eliminated by St. Thomas at 4°C but not at 37°C; and (2) as an additive, nicorandil may fully restore EDHF-mediated endothelial function after prolonged H-R.

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