Effect of pinacidil on rat hearts undergoing hypothermic cardioplegia.
We studied the effect of pinacidil, a potassium-channel opener, on the hemodynamic, biochemical, and ultrastructural changes in rat hearts undergoing hypothermic cardioplegia. Fifty-four male Wistar rats weighing 250 to 300 g were used. Isolated hearts were prepared for modified Langendorff circulation in the working mode using modified Krebs-Henseleit bicarbonate solution bubbled with a 95% O2 and 5% CO2 gas mixture. Eighty minutes of cardioplegia at 25 degrees C was followed by normothermic reperfusion for 30 minutes. Pinacidil, 5, 10, or 50 mumol/L added to the cardioplegic solution, did not affect heart rate, but is significantly improved the recovery of aortic flow as compared with controls (88.1% +/- 4.3 [5 mumol/L]; 83.2% +/- 8.5% [10 mumol/L]; 90.3% +/- 5.3% [50 mumol/L] compared with 55.6 +/- 4.3% [control]; p < 0.05). Administration of pinacidil during reperfusion did not further enhance the recovery of aortic flow. The dose-response curve of aortic flow to the pinacidil concentrations was flat from 5 to 50 mumol/L. However, preservation of myocardial adenosine triphosphate and calcium concentrations and mitochondrial morphology suggested that the optimal concentration of pinacidil cardioplegia is 10 mumol/L.
Department of Thoracic-Cardiovascular Surgery, Tokyo Medical and Dental University, School of Medicine, Japan.
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H
Hosoda
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Sunamori
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A
Suzuki
D000818:Animals; D004305:Dose-Response Relationship, Drug; D006146:Guanidines / Q000008:administration & dosage / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology; D006324:Heart Arrest, Induced; D007036:Hypothermia, Induced; D008297:Male; D015425:Myocardial Reperfusion; D009206:Myocardium / Q000166:cytology; D020110:Pinacidil; D051381:Rats; D017208:Rats, Wistar; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000494:pharmacology*; D016277:Ventricular Function, Left / Q000187:drug effects
D006146:Guanidines; D014665:Vasodilator Agents; D020110:Pinacidil