Contrasting effects of verapamil and nifedipine on pH of ischemic myocardium in the dog.
It remains unknown whether the actions of verapamil to depress and nifedipine to enhance contractile function of ischemic myocardium influence the degree of myocardial ischemic injury. Thus, we measured intramyocardial pH using fiberoptic pH probes in 43 anesthetized open-chest dogs pretreated for 30 min with verapamil, or nifedipine in doses that decreased aortic pressure 10 to 15 mm Hg before ligation of the left anterior descending coronary artery for 15 min. Drugs were continued during the 15-min ischemic period until the animals were euthanized without reperfusion: verapamil, 10-20 micrograms/kg/min and nifedipine, 2 to 4 micrograms/kg/min i.v. Verapamil-treated dogs showed higher pH of ischemic subendocardium after 15 min ischemia (6.75 +/- 0.07) than did the nifedipine (6.48 +/- 0.04) or placebo (6.43 +/- 0.05) groups, even if the animals were paced (6.71 +/- 0.11) to prevent the negative chronotropic effect of verapamil (P less than 0.01). Neither verapamil nor nifedipine changed collateral myocardial blood flow from 0.10 +/- 0.02 in the subendocardium and 0.17 +/- 0.03 ml/min/g in the subepicardium. Left ventricular function estimated by left ventricular dp/dt was depressed 15% by verapamil and enhanced 26% by nifedipine. Thus, verapamil, but not nifedipine, relieves acidosis of ischemic myocardium after acute coronary occlusion in doses that sustain a 10 to 15 mm Hg decrease in aortic pressure. Nifedipine, in doses that produced the same 10 to 15 mm Hg decrease in mean aortic pressure, did not increase intramyocardial pH, as it enhanced contractile function, estimated by left ventricular dp/dt.(ABSTRACT TRUNCATED AT 250 WORDS)
Ro
Y M
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Experimental Physiology and Pharmacology Section, National Heart, Lung and Blood Institute, Bethesda, Maryland.
Markle
D R
DR
Goldstein
S R
SR
Speir
E
E
Greene
R
R
Steadman
K
K
Aamodt
R
R
Epstein
S E
SE
Patterson
R E
RE
D000818:Animals; D003326:Coronary Circulation / Q000187:drug effects; D003327:Coronary Disease / Q000188:drug therapy / Q000378:metabolism*; D004285:Dogs; D006439:Hemodynamics / Q000187:drug effects; D006863:Hydrogen-Ion Concentration; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism*; D009543:Nifedipine / Q000494:pharmacology* / Q000627:therapeutic use; D014700:Verapamil / Q000494:pharmacology*
D014700:Verapamil; D009543:Nifedipine