Influence of pretreatment with phenytoin, lidocaine and quinidine on the cardiodynamic and electrophysiological effects of ouabain in the cat heart-lung preparation
Simaan, J.A.
Archives Internationales de Pharmacodynamie et de Therapie 324: 47-59
1993
ISSN/ISBN: 0003-9780 PMID: 8297185 Document Number: 406283
The effect of pretreatment with phenytoin (diphenylhydantoin), lidocaine, and, for comparison, quinidine, on the doses of ouabain which produce a maximal inotropic effect, onset of arrhythmias and cardiac arrest, was explored in the cat heart-lung preparation. Ouabain was administered as an infusion (0.5 mu-g/min) either alone or after treatment with phenytoin (0.095 +- 0.012 mM), lidocaine (0.090 +- 0.004 mM) or quinidine (0.028 +- 0.006 mM) and the cardiodynamic and electrophysiological changes monitored. Phenytoin, lidocaine and quinidine were administered in doses which were maximally tolerated by the preparations to ensure full effect, as evidenced by early cardiac depression. Ouabain alone produced a maximal increase in contractility prior to the development of arrhythmias at a blood concentration of 0.212 +- 0.014 mu-M, onset of arrhythmias at 0.227 +- 0.015 mu-M, stable ventricular tachycardia at 0.269 +- 0.010 mu-M and cardiac arrest at 0.342 +- 0.014 mu-M. Pretreatment with phenytoin or lidocaine did neither modify these values nor change the pattern of the arrhythmias or the terminal cardiac event. Pretreatment with quinidine prevented the development of ventricular extrasystoles and aberrant ventricular conduction, which were the earliest arrhythmias in all other series. It also made the preparations develop stable ventricular tachycardia at an ouabain blood concentration of 0.246 +- 0.007 mu-M, which was not significantly different from the concentration at which early arrhythmias were noted in the other series. In addition, quinidine decreased the dose of ouabain producing cardiac arrest by 13% but did not modify the terminal event. Pretreatment with phenytoin, lidocaine and quinidine did not affect the electrocardiographic pattern, but at the maximal increase in contractility with ouabain prior to the development of arrhythmias, the PR interval increased to comparable limits with ouabain alone and ouabain after quinidine and lidocaine. However, with ouabain after phenytoin, this increase was 61% less than that with ouabain alone and 31% less than that with ouabain after quinidine. Ouabain given alone or after phenytoin, lidocaine or quinidine produced comparable maximal effects on dp/dt, -dp/dt and left atria) pressure. It may be concluded that pretreatment with phenytoin and lidocaine does not modify the maximal inotropic dose of ouabain prior to the development of arrhythmias, the arrhythmogenic dose or the dose producing cardiac arrest, and that phenytoin partly counters the ouabain-induced depression of AV conduction. Quinidine has an additive effect on the ouabain-induced depression of AV conduction, prevents the ouabain-induced increase in idioventricular rhythm responsible for extrasystoles but not that responsible for ventricular tachycardia, and reduces the dose of ouabain producing cardiac arrest. The discrepancy between these results and reports in the literature in which phenytoin and lidocaine were found to control digitalis-induced arrhythmias when given after arrhythmias developed, cannot be explained from the available data but is more likely to be due to the doses used which may be much higher than those needed to produce only early cardiac depression.