Protection of ischemic hearts by Ca2+ antagonists.
Treatment of isolated, working rat hearts with equiactive conditions of buffer containing low Ca2+ (LC), verapamil (Ver), diltiazem (Dil) or nifedipine (Nif) prior to global ischemia (33 min, 37 degrees C) resulted in an equal enhancement in recovery of contractile function, and high energy phosphate (HEP) stores in reperfused hearts. Treatment only during reperfusion did not enhance recovery or HEP stores. Pretreatment with doses which did not depress preischemic contractile function did not afford protection to globally ischemic hearts. In contrast with Dil (2.5 uM), pretreatment with an equiactive concentration of bepridil (Bep) (20 uM) did not preserve contractile function, HEP, or mitochondrial function and did not reduce Ca2+ overload. The Ca2+ was concentrated in mitochondria of hearts receiving no drug or Bep pretreatment (oxalate-pyroantimonate stain). Increasing concentrations of Ver or Dil given before ischemia resulted in a progressive increase in recovery of contractile function which was proportional to depression of preischemic function. The increase in HEP in these hearts was not proportional to drug concentration, preischemic or postischemic function. Pretreatment with Dil reduced lactate production in both normal and K+-arrested ischemic hearts. Energy preservation is only part of the protective mechanisms of Ca2+ antagonists. The Ca2+ antagonists also reduce Ca2+ overload from reperfusion, and may alter Ca2+ compartmentation during ischemia.
D000818:Animals; D015764:Bepridil; D002118:Calcium / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology / Q000627:therapeutic use*; D003327:Coronary Disease / Q000188:drug therapy*; D004110:Diltiazem / Q000494:pharmacology; D004734:Energy Metabolism; D007773:Lactates / Q000096:biosynthesis; D019344:Lactic Acid; D008929:Mitochondria, Heart / Q000378:metabolism; D009200:Myocardial Contraction / Q000187:drug effects; D009543:Nifedipine / Q000494:pharmacology; D011759:Pyrrolidines / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D014700:Verapamil / Q000494:pharmacology
D002121:Calcium Channel Blockers; D007773:Lactates; D011759:Pyrrolidines; D019344:Lactic Acid; D015764:Bepridil; D014700:Verapamil; D004110:Diltiazem; D009543:Nifedipine; D002118:Calcium