Verapamil protection of ischemic isolated rabbit heart: dependence on pretreatment.
Verapamil may protect ischemic myocardium by several mechanisms: prevention of Ca overload as a direct effect of blocking Ca influx through slow channels, coronary vasodilatation, decreased contractility, or cardioplegia produced by high doses. We manipulated the experimental situation to ask whether the first mechanism alone could be protective. We studied isovolumically contracting rabbit hearts perfused at 37 degrees C, paced at 150/min, and maximally vasodilated by dipyridamole. Hearts were subjected to 60 min of low flow ischemia followed by 60 min reperfusion. Two groups were exposed to verapamil 0.5 microM beginning either 2 to 4 min before ischemia or 10 min after the onset of ischemia (when pressure development had ceased) and continuing until reperfusion. Developed pressure recovered during reperfusion to 70 +/- 4% of its initial value in hearts treated with verapamil before ischemia compared to 40 +/- 5% for control hearts and 35 +/- 11% for hearts treated with verapamil 10 min after the onset of ischemia. There was significant preservation of phosphocreatine at 10 min of ischemia and of ATP at 60 min in the early verapamil group compared to the other two. When verapamil was present before ischemia, pressure development during early ischemia was reduced to about 50% of control. Consequently there was substantial sparing of high energy phosphates and enhanced recovery of mechanical function. If verapamil was added 10 min after the onset of ischemia, when it no longer could affect cardiac work, there was no protection. Therefore, in the isolated rabbit heart, verapamil had an important protective effect only by reducing contractility of ischemic myocardium.
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002118:Calcium / Q000378:metabolism*; D003327:Coronary Disease / Q000503:physiopathology*; D003401:Creatine / Q000378:metabolism; D066298:In Vitro Techniques; D007473:Ion Channels / Q000187:drug effects; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D010725:Phosphocreatine / Q000378:metabolism; D011817:Rabbits; D013326:Strontium Radioisotopes / Q000378:metabolism; D014664:Vasodilation / Q000187:drug effects; D014700:Verapamil / Q000494:pharmacology*
D007473:Ion Channels; D013326:Strontium Radioisotopes; D010725:Phosphocreatine; D000255:Adenosine Triphosphate; D014700:Verapamil; D003401:Creatine; D002118:Calcium