The influence of acidosis on the myocardial uptake and electrocardiographic effects of disopyramide.
The time course for the ECG effects and myocardial uptake of disopyramide was studied in isolated perfused guinea pig hearts under different pH conditions. At pH 7.46 the drug depressed the overall AV conduction time (PR) by 16.64%, the His-ventriculum conduction time (HV interval) by 30.46% and delayed the ventricular repolarization (QT interval) by 8.08%, on average. The maximum intraventricular pressure (Pmax) was also depressed by 35.6%. The maximum effect on the QT interval (constant rate: 0.609 min-1) was reached faster than the maximum effect on the PR and HV intervals (constant rates: 0.399 and 0.400 min-1, respectively), while the myocardium uptake process was complete before any ECG parameter reached a steady state (uptake constant: 1.58 min-1). Under conditions of extracellular acidosis (pH 6.92), the disopyramide disposition parameters (uptake rate constant and myocardial concentration) were not modified. However, the drug exerted significantly smaller effects on the HV and QT intervals and on myocardial contractility. These results are in contrast with those obtained previously with lidocaine and quinidine, and indicate that the influence of acidosis on class 1 antiarrhythmic agents may also depend on the characteristics of the individual drug.
Bova
S
S
Department of Pharmacology, University of Padova, Italy.
Padrini
R
R
Cargnelli
G
G
Piovan
D
D
Ferrari
M
M
D000138:Acidosis / Q000503:physiopathology*; D000818:Animals; D004206:Disopyramide / Q000493:pharmacokinetics / Q000494:pharmacology*; D004562:Electrocardiography / Q000187:drug effects*; D005260:Female; D006168:Guinea Pigs; D006863:Hydrogen-Ion Concentration; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D010477:Perfusion
D004206:Disopyramide