POTASSIUM-CHANNEL OPENER IN CARDIOPLEGIA MAY RESTORE CORONARY ENDOTHELIAL FUNCTION

Background. Depolarizing (hyperkalemic) solutions impair the coronary endothelial function through an endothelium-derived hyperpolarizing fa ctor mechanism, I examined the hypothesis that potassium-channel opene rs may restore the impaired endothelium-derived hyperpolarizing factor -mediated coronary vasorelaxation when added to hyperkalemic cardiople gia. Methods. The porcine coronary arteries were exposed to hyperkalem ia (potassium, 20 or 50 mmol/L) or hyperkalemia plus the potassium-cha nnel opener aprikalim at 0.1 mmo/L for 1 hour. Endothelium-derived hyp erpolarizing factor-mediated relaxation (percentage of 30 nmol/L U4661 9 precontraction) was induced by calcium ionophore A23187 and bradykin in in the presence of indomethacin (7 mu mol/L) and N omega-nitro-L-ar ginine (300 mu mol/L). Results. The endothelium-derived hyperpolarizin g factor-mediated relaxation was significantly impaired by exposure to hyperkalemia (20 mmol/L: 24.9% +/- 14.1% versus 88.0% +/- 3.3% in con trol, 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 signifi cantly recovered by addition of aprikalim into the hyperkalemic (20 mm ol/L) solution in A23187 experiments (81.2% +/- 4.8%, p = 0.002) but o nly slightly recovered when added into the higher concentration of pot assium (50 mmol/L) in bradykinin experiments (56.1% +/- 4.7%, p = 0.2) . Conclusions. Potassium-channel openers may preserve endothelium-deri ved 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 r eaches 50 mmol/L. This study may provide new insights into cardioprote ction during open heart operations. (Ann Thorac Surg 1998;66:1318-22) (C) 1998 by The Society of Thoracic Surgeons