Myung S. Yoon

The role of local disparity in conduction and recovery time on ventricular vulnerability to fibrillation

Summary In experiments on 16 mongrel dogs, conduction time (CT), local refractory periods (RP), and recovery time (RT) of conducted beats were measured in the ventricles under local coronary perfusion and under systemic intravenous infusion with potassium chloride or epinephrine. The values of these parameters found in the locally perfused and in the non-perfused areas and the degree of local dispersion of these values were correlated with ventricular fibrillation thresholds. Regardless of potassium or epinephrine infusion, ventricular vulnerability to fibrillation was significantly lower with local infusions than with systemic infusions. It was found that changes of CT, RP, and RT in either direction would occur with increased and decreased fibrillation thresholds, and they were not directly correlated to ventricular vulnerability to fibrillation. The local dispersion of these parameters between the perfused and non-perfused areas, however, was always increased when ventricular vulnerability was high, and decreased when ventricular vulnerability was low. These results are strong evidence supporting the importance of local dispersion in excitability. The local dispersion was best represented by local variation in the RT of conducted beats, which under all experimental conditions correlated best with ventricular vulnerability. The other electrophysiological parameters seem to be of importance for the ventricular vulnerability when they contribute to an increased or decreased local dispersion of excitability.

Effects of verapamil on ventricular rhythm during acute coronary occlusion

The effects of verapamil on electrophysiologic parameters of the ventricle were studied during acute coronary occlusion in anesthetized open-chest dogs. Those parameters measured in the study were idioventricular automaticity, ventricular conduction, and fibrillation threshold. The incidence of rapidly repetitive beats and fibrillation induced by two successive premature beats was also studied. Verapamil significantly decreased idioventricular automaticity (in five dogs), improved conduction through the ischemic area (in six dogs), and increased fibrillation threshold of the ischemic ventricular (in eight dogs). The drug was effective in abolishing rapidly repetitive beats and fibrillation induced by closely coupled premature beats during acute coronary occlusion. Rapidly repetitive beats occurred in nine out of 15 dogs and these repetitive beats were degenerated into fibrillation in seven dogs before verapamil. Following pretreatment with the drug, rapidly repetitive beats and fibrillation occurred in none of the 15 dogs. The results indicate that verapamil can be very effective against ventricular arrhythmias occurring in association with myocardial infarction.

Effects of vagal stimulation, atropine, and propranolol on fibrillation threshold of normal and ischemic ventricles.

The effects of electrical stimulation of the vagus nerves and the administration of atropine on ventricular fibrillation threshold (VFT) were studied in open-chest hearts of 15 dogs anesthetized by alpha-chloralose. These studies were made in both normal and ischemic ventricles, i.e., before and during acute coronary occlusion. The ventricles were paces at a constant rate to eliminate rate-dependent changes and the minimal current required to induce ventricular fibrillation (or VFT) was determined by delivering a train of rapid rectanglular pulses (100 per second) to the venticle actoss the vulnerable period. In normal ventricles, VFTs were significantly increased by vagal stimulation (P less than 0.01) and decreased by atropine (P less than 0.05). Coronary occlusion markedly decreased VFTs (P less than 0.01), and vagal stimulation or atropine failed to alter VFTs significantly in these ischemic ventricles (P greater than 0.8). In additional 14 dogs, the effects of vagal stimulation and atropine were studied after the administration of propranolol. Propranolol alone increased VFTs significantly in boetreatment with propranolol, vagal stimulation and atropine failed to change VFTs significantly in both normal and ischemic ventricles (P greater than 0.8). These results indicate that the vagus nerves exert their effect on VFT by modifying the sympathetic nerve activity in normal ventricles, but such an effect is not significant enough to alter VFT in ischemic ventricles.

Effects of unipolar cathodal and bipolar stimulation on vulnerability of ischemic ventricles to fibrillation

The effects of unipolar and bipolar stimulation on ventricular fibrillation threshold were studied during acute occlusion of the left anterior descending coronary artery in 13 anesthetized dogs. Values for ventricular fibrillation threshold were determined by delivering trains of rapid bipolar or unipolar pulses (100/sec) during the vulnerable period. The mean threshold value was found to be 13.0 ma for bipolar, 13.9 ma for unipolar anodal and 21.0 ma for unipolar cathodal stimulation. Ventricular fibrillation threshold was significantly lower (P less than 0.01) with both unipolar anodal and bipolar stimulation than with unipolar cathodal stimulation. In these animals, the first premature beats induced by the rapid stimuli occurred significantly earlier with unipolar anodal and bipolar stimulation than with unipolar cathodal stimulation. The effect of competition of unipolar or bipolar pacing stimuli with normally conducted ventricular beats was also studied in a group of 16 dogs. Repeated trials of competitive pacing during coronary occlusion showed that the incidence of ventricular fibrillation was significantly greater (P less 0.05) with bipolar pacing (36 percent) than with unipolar cathodal pacing (15 percent). These results indicate that bipolar pacing is potentially more dangerous than unipolar cathodal pacing and suggest that the incidence of pacemaker-induced ventricular fibrillation might be further reduced by the use of unipolar cathodal stimulation during acute myocardial infarction.

Effect of procainamide on fibrillation threshold of normal and ischemic ventricles

Abstract The effect of procainamide on ventricular fibrillation threshold was studied in anesthetized open chest hearts in 12 dogs without coronary occlusion and in 11 dogs during acute coronary occlusion. The minimal current required to induce ventricular fibrillation was determined by delivering a train of rapid rectangular pulses (100/sec) to the ventricle during its vulnerable period. Procainamide was administered as a single intravenous injection in a dose of 10 to 20 mg/kg body weight. Blood levels of the drug reached their peak immediately, fell to therapeutic levels (5 to 10 μg/ml) within about 30 minutes and then remained at those levels up to 80 minutes after the injection. The effect of procainamide on the fibrillation threshold correlated with procainamide blood levels. The increase, peak level and decrease in blood concentration paralleled changes in fibrillation threshold. Procainamide at therapeutic blood levels increased the mean fibrillation threshold from the control value of 16 to 30 ma (88 percent increase) in the normal ventricles. The effect was less pronounced during acute coronary occlusion, and the mean fibrillation threshold increased from 8 to 13 ma (63 percent increase) at therapeutic procainamide blood levels. In addition, procainamide failed to produce complete reversion of the decreased fibrillation threshold to the normal value during acute myocardial ischemia.

Effects of thioridazine (Mellaril) on ventricular electrophysiologic properties

The effects of therapeutic and toxic doses of thioridazine (Mellaril) (10 and 50 mg/kg body weight, respectively) on ventricular electrophysiologic properties were studied in 12 anesthetized dogs. Threshold pacing currents (diastolic threshold), effective refractory period and conduction time were significantly increased, and idioventricular automaticity was suppressed after administration of 10 mg/kg of thioridazine; the effects were much more pronounced after administration of 50 mg/kg. Rapidly repetitive responses or tachycardia could be induced in the ventricle by two early premature beats in 9 of the 12 dogs after the 50 mg/kg dose, but they did not occur before drug administration or after the 10 mg/kg dose. These results indicate that the antiarrhythmic and arrhythmogenic effects of thioridazine are dose-dependent and that careful monitoring with frequent electrocardiograms is needed for patients receiving large doses of this drug.

Effect of procainamide and lidocaine on ventricular automaticity and reentry during acute coronary occlusion

Abstract A model was developed to study ventricular automaticity and reentry in the heart of open chest dogs during myocardlal ischemia. Atrioventricular (A-V) block and the resultant idioventricular rhythm were induced by surgical destruction of the His bundle, and acute myocardial ischemia was produced by ligation of the left anterior descending coronary artery. The ventricle was paced by basic stimuli, and one or two premature beats were introduced at various coupling Intervals after the 10th basic beat. Two different types of response to these premature beats could be observed: (1) rapidly repetitive beats or fibrillation due to reentry after early premature beats, and (2) the appearance of escape beats from idioventricular automatic fibers after late premature beats. With this model of ventricular reentry and automaticity, the effect of procainamide (group I antiarrhythmic agent) was studied in 12 dogs, and that of lidocaine (group II) in 13 dogs. Both procainamide and lidocaine were effective in decreasing automaticity since they significantly increased postextrasystolic escape intervals of idloventricular beats. Although procainamide failed to abolish the reentrant beats induced by early premature beats in all 12 dogs, lidocaine abolished these beats in 10 of 13 dogs. The results indicate that lidocaine is much more effective than procainamide in preventing ventricular reentrant activity induced by early premature beats.

Effect of ventricular aberrancy on fibrillation threshold

VFTs were determined in 12 open-chest dogs at epicardial sites in the right and left ventricles (RV and LV) following normally or aberrantly conducted beats. The normal beats were produced by right atrial pacing, and the aberrant beats by surgical RBBB or ventricular pacing at an RV or LV site. The mean VFT following normal beats was 21.2 plus or minus 1.8 ma. in RV and 23.0 plus or minus 2.7 ma. in LV. The mean VFT following aberrant beats of RBBB was 21.3 plus or minus 2.6 ma. in RV and 25.0 plus or minus 2.8 ma. in LV. The difference between the mean VFT of normal beats and that of aberrant beats was not statistically significant. The mean values of VFTs determined in RV or LV following aberrant beats produced by pacing of the contralateral ventricle were not significantly different from those of the normal beats. The mean VFT was 22.9 plus or minus 3.1 ma. in RV and 20.1 plus or minus 2.1 ma. in LV. These results indicate that the aberrancy of ventricular beats per se is not associated with decreased VFT or increased ventricular vulnerability to fibrillation. The most predictable observation was that the mean VFTs were significantly lower in both ventricles when they were determined at the site of application of pacing stimuli. The mean values were 12.4 plus or minus 1.2 ma. in RV and 13.6 plus or minus 1.6 ma. in LV. This decrease in VFT may be due to slow conduction and increased asynchrony of recovery of excitability at or near the site of application of pacing stimuli.

Electrophysiologic effects of mexiletine on normal and ischemic ventricles.

The effects of mexiletine on ventricular electrophysiologic properties were studied in seven normal and ten ischemic canine ventricles. Ventricular fibrillation threshold was significantly increased and idioventricular automaticity was significantly suppressed after intravenous administration of 2 mg/kg of mexiletine. Diastolic threshold, effective refractory period and ventricular conduction time were all increased slightly after the drug administration, although the changes were not statistically significant. Rapidly repetitive responses and/or fibrillation were induced in the ischemic ventricle by two early premature beats in six of ten dogs, but these serious arrhythmias could be induced in none of the ten dogs after mexiletine pretreatment. The study indicates that the mode of action of mexiletine is similar to that of lidocaine and the drug is an effective antiarrhythmic agent in preventing ventricular arrhythmias in dog ventricles during myocardial ischemia.

Facilitation of A-V nodal reciprocation by procainamide*

Procainamide is known to depress conduction through the A-V node, and this property may facilitate the development of ventricular reciprocal beats or echoes. The occurrence of ventricular reciprocal beats was studied in 20 open-chest dogs before and after the administration of procainamide. While the ventricle was paced by basic stimuli, early ventricular premature beats were introduced at various coupling intervals to induce ventricular echoes. When ventricular echoes could be induced in a given heart, there was a continuous range of coupling intervals (or echo zone) within which ventricular echoes occurred. In the control state, no echo occurred in eight dogs and the echoes developed in 12 dogs with the mean echo zone of 38.3 msec. The effect of procainamide was studied at its therapeutic blood levels about 25 minutes after an intravenous injection of the drug in a dose of 10 mg. per kilogram. Of the first group of eight dogs, in which no echo occurred in the control state, four dogs developed ventricular echoes after the administration of procainamide with the mean echo zone of 29.3 msec. for the group. Of the second group of 12 dogs, in which ventricular echoes were induced in the control state, the administration of procainamide increased the echo zone in 10 dogs with the mean echo zone of 67.8 msec. for the group. Ventricular reciprocal beats were often sustained to produce short runs of supraventricular tachycardia in five dogs after the administration of procainamide. The results demonstrated a potentially deleterious effect of procainamide in facilitating the inducation of A-V nodal reciprocation by closely coupled ventricular premature beats.