| Budget Amount *help |
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1989: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1988: ¥1,200,000 (Direct Cost: ¥1,200,000)
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| Research Abstract |
Extracellular potassium accumulation during acute myocardial ischemia has been implicated as a major cause of ventricular arrhythmias. However, the cause of the increased net outward movement of K^+ observed after acute coronary occlusion is not fully understood. This study was undertaken to determine whether an increase in outward current resulting from depletion of intracellular ATP is involved in potassium efflux from ischemic heart cells and a shortening of action potential duration (APD). Two sulfonyl-ureas, tolbutamide (2 mM) and glibenclamide (20 uM) inhibited the openings of the ATP- sensitive K^+ channels to the same extent in the open cell-attached patch of guinea-pig ventricular cells. These sulfonylureas completely antagonized the APD shortening induced by pinacidil (100 uM), a K^+ channel opener, in isolated guinea-pig papillary muscles.
However, tolbutamide potentiated the APD shortening in the hypoxic, glucose-free condition. Glibenclamide lessened but failed to abolish t
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he APD shortening in the hypoxic, glucose-free condition. In the papillary muscles exposed to a glucose-free solution containing dinitrophenol, tolbutamide unchanged while glibenclamide improved the APD shortening. In isolated right ventricular free wall preparation of the dog heart, experimental ischemia was produced by discontinuing the perfusion with oxygenated Tyrode solution through the coronary artery. Again, glibenclamide (20 uM) lessened but failed to abolish the APD shortening during myocardial ischemia. In anesthetized dogs, myocardial ischemia was produced by occlusion of the left anterior descending coronary artery, and changes in extracellular potassium and lactate concentrations were evaluated using micro- dialysis method. Increases in potassium and lactate concentrations of the effluent from the microdialysis tubes inserted into the ischemic myocardium were observed during coronary occlusion of 30 min. Pretreatment with glibenclamide (1 mg/kg) failed to decrease the potassium concentration of the effluent although it slightly decreased the lactate concentration. These findings suggest that an increase in outward current through ATP-sensitive K^+ channels may not play a major role in the potassium efflux during myocardial ischemia. Less
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