Bromocriptine treatment of digitalis-induced ventricular tachyarrhythmias: studies in a canine model.

Ventricular tachyarrhythmias associated with digitalis toxicity are believed to be due, in part, to cardiac glycoside-mediated increased central sympathetic neural activity. Because dopaminergic receptor agonists reduce sympathetic outflow, this study assessed effectiveness of the available dopaminergic agonist, bromocriptine, in slowing or terminating ouabain-induced ventricular tachycardia in anesthetized dogs. In all experiments, ouabain was administered intravenously (20 micrograms/kg body weight bolus injection, followed by 2.5 micrograms/kg per min infusion) until the onset of stable ventricular tachycardia. Of seven untreated dogs (Group 1), ouabain-induced ventricular tachyarrhythmias resulted in ventricular fibrillation in three, while in four dogs tachycardia persisted without significant change in rate until the study was terminated. Fourteen dogs (Group 2) received bromocriptine, either 30 micrograms/kg (Group 2A) or 50 micrograms/kg (Group 2B), after the onset of ventricular tachycardia. Tachycardia slowed in all 14 dogs and terminated with resumption of sinus rhythm in 8 of the 14. In all six dogs pretreated with the peripheral dopaminergic antagonist domperidone (Group 3), bromocriptine, 50 micrograms/kg, slowed ventricular tachycardia and in three of the six, tachycardia terminated. In contrast, of five dogs pretreated with haloperidol, a central and peripheral dopaminergic receptor antagonist (Group 4), bromocriptine, 50 micrograms/kg, failed to slow ventricular tachycardia in three, and two of the three developed ventricular fibrillation. In summary, the dopaminergic receptor agonist, bromocriptine, presumably acting at central dopaminergic receptor sites, consistently slowed and in most cases reversed ouabain-induced ventricular tachycardia in a canine model.

Cellular electrophysiological changes in "round heart disease" of turkeys: a potential basis for dysrhythmias in myopathic ventricles.

Arrhythmias are commonly recorded in "round heart disease", a presumed viral, congestive cardiomyopathy of turkeys. To assess whether cellular electrophysiological changes may be associated with arrhythmia susceptibility, we compared transmembrane action potential characteristics in left and right ventricular endocardial muscle fibres from 19 inbred myopathic turkeys with findings in 13 normal control turkeys (age 1 to 74 days). In left ventricular tissue, as a group, action potential duration at 50% repolarisation (APD50) was reduced in myopathic hearts (201+/-6(SEM) vs 228+/-9 ms in controls. P less than 0.01), while the maximum rate of phase 0 (dV/dtmax) action potential amplitude, diastolic resting membrane potential and action potential duration at 90% repolarisation (APD90) did not differ from control turkeys. By contrast, in myopathic right ventricular tissue, as a group, both APD50 (186+/-5 vs 206+/-4 ms in controls) and APD90 (208+/-4 vs 228+/-3 ms in controls) were shorter (P less than 0.01). The plateau potential in both right and left ventricular tissue was significantly higher in inbred turkeys. Since a spectrum of cardiac dilatation and hypertrophy is present in myopathic turkeys, we examined the effect of hypertrophy on action potential characteristics. In "round heart disease" turkeys, left ventricular hypertrophy was characterised by reduced dV/dtmax (98+/- vs 274+/-26 V.s-1, P less than 0.01) and right ventricular hypertrophy by further shortening of both APD50 (174+/-7 vs 202+/-6 ms, P less than 0.01) and APD90 (193+/- vs 224+/-5 ms, P less than 0.01), but no change in dV/dtmax (105+/-13 vs 120+/-9 V.s-1, P = NS). These results indicate that certain electrophysiological differences (eg reduced action potential duration), may, in part, contribute to dysrhythmia susceptibility in this presumed viral cardiomyopathy model.

Cellular electrophysiologic effects of dexamethasone sodium phosphate: implications for cardiac stimulation with steroid-eluting electrodes.

Impregnation of implantable cardiac pacemaker electrodes with dexamethasone sodium phosphate dexamethasone) has been associated with reduced energy requirements for both atrial and ventricular stimulation. To determine whether cardiac cellular electrophysiologic effects of dexamethasone could in part account for lower stimulation thresholds, conventional microelectrode recording and stimulation techniques were used to assess both the immediate (acute) effects of dexamethasone (10(-6) and 10(-4) M) in superfused isolated rabbit right atrial and right ventricular preparations, and chronic effects in rabbit right ventricular tissue following 2 weeks of either daily parenteral dexamethasone (5 mg/kg, plasma concentration approximately 1 to 5 x 10(-5) M) or saline placebo injections. In acute superfusion studies, dexamethasone resulted in a concentration dependent prolongation of spontaneous right atrial cycle length, but did not significantly affect right atrial transmembrane action potential characteristics or refractoriness. However, acute dexamethasone superfusion tended to increase right ventricular resting membrane potential and diminish stimulation threshold. On the other hand, compared to findings in saline-injected control rabbits, chronic dexamethasone injection had little effect on right ventricular stimulation threshold transmembrane action potential characteristics, or right ventricular refractoriness. Thus, the acute direct electrophysiologic effects of high-dose dexamethasone are compatible with the early reduction of cardiac stimulation thresholds associated with dexamethasone impregnated pacing electrodes. On the other hand, electrophysiologic findings in the presence of chronic dexamethasone exposure do not fully account for long-term reduction of stimulation energy requirements.

Electrophysiological effects of transient aortic occlusion in intact canine heart.

This study utilized sonomicrometers transmural multipolar electrodes and cardiac electrical stimulation techniques to examine the effect on myocardial electrophysiological characteristics of altering ventricular systolic mechanical properties by transient aortic occlusion. Nine anesthetized open-chest dogs were atrially paced, and timed extrastimuli were inserted during alternate drive-train sequences at right or left ventricular (RV, LV) epicardial sites to measure ventricular effective refractory period (ERP). Sonomicrometer measurements of LV systolic mechanical parameters and both RV and LV electrophysiological findings were determined prior to and during periods of transient aortic occlusion. Aortic occlusion was applied just prior to the last beat of each eight-beat atrial drive train and released immediately following the programmed ventricular extrastimulus. Aortic occlusion increased LV systolic pressure (+42 +/- 26.6 mmHg, P less than 0.01) and diminished segmental stroke shortening (0.100 +/- 0.059 mm, P less than 0.02), shortening fraction (0.086 +/- 0.048, P less than 0.001), mean velocity of stroke shortening (0.444 +/- 0.186 mm/s, P less than 0.001), and stroke work (P less than 0.001). LV epicardial and endocardial ERP were prolonged as a result of aortic occlusion (5 +/- 7.2 and 6 +/- 6.5 ms, respectively, P less than 0.05), whereas RV ERP was unchanged. Latency of premature beats at equivalent coupling intervals was unaltered. ERP prolongation correlated most strongly with reductions of segmental stroke shortening (r = 0.928, P less than 0.001), shortening fraction (r = 0.901, P less than 0.001), and mean shortening velocity (r = 0.819, P less than 0.01). Thus transient aortic occlusion prolonged LV refractoriness, and electrophysiological changes closely paralleled the severity of systolic mechanical disturbance.