Potassium-channel opener in cardioplegia may restore coronary endothelial function.
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 micromol/L) and Nomega-nitro-L-arginine (300 micromol/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.
He
G W
GW
Department of Surgery, University of Hong Kong, Grantham Hospital, Aberdeen. gwhe@hkucc.hku.hk
D000818:Animals; D001639:Bicarbonates / Q000494:pharmacology; D002122:Calcium Chloride / Q000494:pharmacology; D002314:Cardioplegic Solutions / Q000737:chemistry* / Q000494:pharmacology; D003331:Coronary Vessels / Q000187:drug effects*; D004730:Endothelium, Vascular / Q000187:drug effects*; D005260:Female; D008274:Magnesium / Q000494:pharmacology; D008297:Male; D010847:Picolines / Q000494:pharmacology*; D015221:Potassium Channels / Q000187:drug effects*; D011189:Potassium Chloride / Q000494:pharmacology; D011714:Pyrans / Q000494:pharmacology*; D012965:Sodium Chloride / Q000494:pharmacology; D013552:Swine; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology*
D001639:Bicarbonates; D002314:Cardioplegic Solutions; D010847:Picolines; D015221:Potassium Channels; D011714:Pyrans; C041711:St. Thomas' Hospital cardioplegic solution; D014665:Vasodilator Agents; C061043:aprikalim; D012965:Sodium Chloride; D011189:Potassium Chloride; D008274:Magnesium; D002122:Calcium Chloride