Myocardial uptake and pharmacodynamics of quinidine and propafenone in isolated rabbit hearts: metabolic versus respiratory acidosis.
The influence of metabolic and respiratory acidosis on the myocardial accumulation and pharmacodynamics of quinidine and propafenone was studied in isolated perfused rabbit hearts. Three pH groups were evaluated: physiologic buffer, pH 7.4; metabolic acidosis, pH 7.0; and respiratory acidosis, pH 7.0. Myocardial accumulation of quinidine and propafenone was significantly reduced during acidosis. Although myocardial quinidine concentrations were similar in the metabolic acidosis group (14.4 +/- 1.2 micrograms/g) and the respiratory acidosis group (14.5 +/- 1.3 micrograms/g), the myocardial propafenone concentration was significantly less during metabolic acidosis (8.9 +/- 2.0 micrograms/g) as compared with respiratory acidosis (12.7 +/- 2.4 micrograms/g, p less than 0.05). The myocardial concentration-effect relationships were linear over the observed myocardial concentration ranges. The slopes of the linear concentration-effect relationships describing QRS duration were increased twofold by both types of acidosis as compared with normal pH (p less than 0.05). In contrast, the slopes of the concentration-effect relationships describing changes in ventricular repolarization and refractoriness were increased only during metabolic acidosis as compared with pH 7.4 (p less than 0.05). Thus, for any given concentration of drugs, the effects of quinidine and propafenone on ventricular conduction time are dependent on the pH of the perfusate, whereas these drug effects on ventricular repolarization and refractoriness are dependent on the buffer composition.
Gillis
A M
AM
Department of Medicine, University of Calgary, Alberta, Canada.
Keashly
R
R
D000138:Acidosis / Q000378:metabolism*; D000142:Acidosis, Respiratory / Q000378:metabolism*; D000818:Animals; D003326:Coronary Circulation / Q000187:drug effects; D004562:Electrocardiography; D006321:Heart / Q000187:drug effects*; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D011405:Propafenone / Q000493:pharmacokinetics / Q000494:pharmacology*; D011802:Quinidine / Q000493:pharmacokinetics / Q000494:pharmacology*; D011817:Rabbits
D011405:Propafenone; D011802:Quinidine