HYPERKALEMIA EXPOSURE IMPAIRS EDHF-MEDIATED ENDOTHELIAL FUNCTION IN THE HUMAN CORONARY-ARTERY

Background. My colleagues and I have found in the porcine coronary art ery that the pathway other than the nitric oxide (N-G-nitro-L-arginine [L-NNA]-sensitive) and cyclooxygenase (indomethacin-sensitive) pathwa ys of endothelium-dependent relaxation, related to the endothelium-der ived hyperpolarizing factor (K+ channel-related), are altered after ex posure to hyperkalemia. The present study was designed to examine whet her this effect exists in the human coronary artery. Methods. Coronary artery rings obtained from explanted fresh human hearts were studied in organ chambers under physiologic pressure. The endothelium-dependen t relaxation in response to calcium ionophore A23187 was studied in U4 6619 (30 nmol/L)-induced precontraction in the presence of the cycloox ygenase inhibitor indomethacin (7 mu mol/L) and the nitric oxide biosy nthesis inhibitor L-NNA (300 mu mol/L). The effect of incubation with 20 mmol/L K+ for 1 hour on the relaxation was examined in other corona ry rings. Results. In control rings, A23187 induced a maximal relaxati on of 50.7% +/- 3.2% (n = 6). After 1 hour of exposure to 20 mmol/L K, the relaxation was reduced to 30.4% +/- 4.6% (n = 6; p = 0.005). Inc ubation with hyperkalemia also significantly reduced the sensitivity ( increased effective concentration that caused 50% of maximal relaxatio n) of the indomethacin- and L-NNA-resistant relaxation (-7.37 +/- 0.17 versus -8.28 +/- 0.27 log mol/L; p = 0.019). Conclusions. Exposure to hyperkalemia reduces the indomethacin- and L-NNA-resistant, endotheli um-dependent (endothelium-derived hyperpolarizing factor-related) rela xation in the human coronary artery. This suggests that the previously proposed mechanism of coronary dysfunction after exposure to cardiopl egic and organ preservation solutions in animal vessels is also valid in the human heart. (C) 1997 by The Society of Thoracic Surgeons