Electrophysiologic and mechanical evidence of superiority of hyperpolarizing versus depolarizing cardioplegia in protection of endothelium-derived hyperpolarizing factor-mediated endothelial function: a study in coronary resistance arteries

OBJECTIVE: The advantages of hyperpolarizing cardioplegia with potassium-channel openers versus depolarizing cardioplegia have been suggested but not demonstrated in coronary microarteries. This study examined the simultaneous electric and tonic alteration of coronary microarteries at the cellular level during and after exposure to depolarizing cardioplegia or hyperpolarizing cardioplegia, with emphasis on endothelium-derived hyperpolarizing factor-mediated relaxation and hyperpolarization. METHODS: Porcine coronary microarteries (diameter, approximately 200-400 microm) were incubated with depolarizing cardioplegia (20 mmol/L KCl) or hyperpolarizing cardioplegia (10 micromol/L aprikalim) for 1 hour. Cellular membrane potential with a glass microelectrode in a coronary smooth muscle cell and isometric force of the muscle were simultaneously measured in a myograph. RESULTS: Depolarizing cardioplegia incubation produced a stable contraction (from 4.9 +/- 0.3 mN to 7.3 +/- 0.4 mN) and depolarization (from -51 +/- 1 mV to -41 +/- 2 mV). In contrast, hyperpolarizing cardioplegia relaxed (from 4.8 +/- 0.3 mN to 3.5 +/- 0.3 mN) and hyperpolarized (from -51 +/- 2 mV to -56 +/- 1 mV) the smooth muscle. After exposure to depolarizing cardioplegia, the bradykinin-induced, endothelium-derived hyperpolarizing factor-mediated relaxation reduced from 66.2% +/- 5.0% to 18.4% +/- 3.7% (P <.001), and the membrane hyperpolarization reduced from 18 +/- 1 mV to 7 +/- 1 mV (P <.001) in the presence of indomethacin and N(G)-nitro-L-arginine. In contrast, hyperpolarizing cardioplegia did not affect the bradykinin-induced responses. CONCLUSIONS: In the coronary microarteries, exposure to hyperpolarizing cardioplegia preserves whereas depolarizing cardioplegia reduces the endothelium-derived hyperpolarizing factor-mediated electric (hyperpolarization) and mechanical (relaxation) responses. Thus hyperpolarizing cardioplegia is superior to depolarizing cardioplegia in protecting the endothelial function in the coronary microcirculation.