Abstract :
Background. Depolarizing (hyperkalemic) solutions impair the coronary endothelial function through an endothelium-derived hyperpolarizing factor mechanism. I examined the hypothesis that potassium-channel openers may restore the impaired endothelium-derived hyperpolarizing factor-mediated coronary vasorelaxation when added to hyperkalemic cardioplegia.
Methods. The porcine coronary arteries were exposed to hyperkalemia (potassium, 20 or 50 mmol/L) or hyperkalemia plus the potassium-channel opener aprikalim at 0.1 mmol/L for 1 hour. Endothelium-derived hyperpolarizing factor-mediated relaxation (percentage of 30 nmol/L U46619 precontraction) was induced by calcium ionophore A23187 and bradykinin in the presence of indomethacin (7 μmol/L) and Nω-nitro- -arginine (300 μmol/L).
Results. The endothelium-derived hyperpolarizing factor-mediated relaxation was significantly impaired by exposure to hyperkalemia (20 mmol/L: 24.9% ± 14.1% versus 88.0% ± 3.3% in control, p = 0.002 for A23187; 50 mmol/L: 40.5% ± 12.3% versus 76.5% ± 3.8%, p = 0.003 for bradykinin). This reduced relaxation was significantly recovered by addition of aprikalim into the hyperkalemic (20 mmol/L) solution in A23187 experiments (81.2% ± 4.8%, p = 0.002) but only slightly recovered when added into the higher concentration of potassium (50 mmol/L) in bradykinin experiments (56.1% ± 4.7%, p = 0.2).
Conclusions. Potassium-channel openers may preserve endothelium-derived hyperpolarizing factor-mediated coronary relaxation when added to traditional hyperkalemic cardioplegia. This effect is significant when the potassium concentration is 20 mmol/L but partially lost when it reaches 50 mmol/L. This study may provide new insights into cardioprotection during open heart operations.
