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 micrograms/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 microM, onset of arrythmias at 0.227 +/- 0.015 microM, stable
ventricular tachycardia at 0.269 +/- 0.010 microM and
cardiac arrest at 0.342 +/- 0.014 microM. 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 microM, 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 atrial 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.(ABSTRACT TRUNCATED AT 400 WORDS)