Effects of diltiazem and propranolol on irreversibility of ischemic cardiac function and metabolism in the isolated perfused rat heart.
Ischemia was induced by lowering the afterload pressure of the perfused working rat heart, and continued until the heart was reperfused by raising the after load. After ischemia, the following changes were observed: decreases in the pressure-rate product (peak aortic pressure X heart rate) and coronary flow; depletion of adenosine triphosphate and creating phosphate; and accumulation of lactate. When the heart was exposed to ischemia for more than 20 min, reperfusion of the ischemic heart could not restore the pressure-rate product and the tissue adenosine triphosphate completely, suggesting that irreversible ischemic damage occurred. Diltiazem (2.41 X 10(-6), 1.21 X 10(-5), and 2.41 X 10(-5) M) or propranolol (1.69 X 10(-5) and 3.38 X 10(-5) M) was provided for the heart 5 min before the onset of ischemia. In the presence of diltiazem or propranolol, the levels of adenosine triphosphate and creatine phosphate were preserved even after 20 min of ischemia. Reperfusion with the normal perfusate after 20 min of ischemia. Reperfusion with the normal perfusate after 20 min of ischemia with the buffer containing diltiazem or propranolol recovered the pressure-rate product that had been decreased by ischemia, depending on the concentration of diltiazem or propranolol provided. These results indicate that diltiazem, as well as propranolol, delays the onset of irreversible ischemic damage of the heart, suggesting their protective effects on the ischemic myocardium.
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001552:Benzazepines / Q000494:pharmacology*; D003327:Coronary Disease / Q000188:drug therapy* / Q000378:metabolism; D004110:Diltiazem / Q000494:pharmacology*; D006321:Heart / Q000502:physiology*; D066298:In Vitro Techniques; D007773:Lactates / Q000378:metabolism; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D010477:Perfusion; D010725:Phosphocreatine / Q000378:metabolism; D011433:Propranolol / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
D001552:Benzazepines; D007773:Lactates; D010725:Phosphocreatine; D000255:Adenosine Triphosphate; D011433:Propranolol; D004110:Diltiazem