Superiority of hyperpolarizing to depolarizing cardioplegia in protection of coronary endothelial function

Objective: Hyperpolarizing cardioplegia has recently been proposed for myocardial protection, To compare the protective effect of hyperpolarizing cardioplegia and depolarizing (hyperkalemic) cardioplegia on coronary endothelium, we studied porcine coronary arteries in the organ chamber, Methods: Relaxation mediated by the endothelium-derived hyperpolarizing factor (EDHF) was used as the index of endothelial function because (1) hyperkalemia without ischemia does not impair the nitric oxide-mediated function according to previous studies and (2) EDHF relaxes vessels by hyperpolarizing the membrane potential. Therefore depolarizing cardioplegia may inhibit this function, but hyperpolarizing cardioplegia may preserve it. EDHF-mediated relaxation was induced by bradykinin and the calcium ionophore A23187 with the presence of indomethacin (7 mu mol/L; INN: indometacin), a cyclooxygenase inhibitor, and N-G-nitro-L-arginine (300 mu mol), a nitric oxide biosynthesis inhibitor in U46619 (30 nmol/L)-induced precontraction, The vessels were exposed to either hyperpolarizing cardioplegic solution (the potassium-channel opener aprikalim, 0.1 mmol/L) or depolarizing cardioplegic solution (high potassium concentration, 20 mmol/L for A23187 and 50 mmol/L for bradykinin experiments) for 1 hour with a constant supply of oxygen to exclude the effect of ischemia. Results: EDHF-mediated relaxation was significantly impaired in either A23187 or bradykinin studies (80.1% +/- 7.5% vs 24.9% +/- 14.2%, p = 0.004, n = 8 in each group for A23187, and 71.4% +/- 4.7%, n = 13, vs 40.5% +/- 12.9%, n = 7, p = 0.01, for bradykinin). The effective concentration causing 50% of maximal relaxation was significantly increased in the A23187 experiments with the treatment of hyperkalemia. In contrast, in aprikalim-treated arteries, the EDHF-mediated relaxation induced by either A23187 or bradykinin was unchanged. Conclusions: We conclude that EDHF-mediated coronary endothelial function is maximally preserved by hyperpolarizing cardioplegia but impaired by depolarizing cardioplegia. These findings support the use of hyperpolarizing cardioplegia in cardiac operations.