We made continuous electrocardiographic recordings on magnetic tape during 15 episodes of ischemia in five patients with variant angina to determine the characteristics of the QRS changes. Orthogonal leads were used and the electrocardiograms were analyzed visually and by digital computer. Changes were quantified by subtracting baseline electrocardiograms from those obtained during ischemia. Large changes in the QRS occurred during ischemia but the waveform quickly returned to baseline when the episode subsided. In all patients there was prolongation of the QRS duration and an increase in QRS voltage during the terminal 40 msec of the waveform in the lead(s) showing the most marked ST displacement. The increase in the terminal QRS could be represented by a vector directed toward the ischemic zone. In a given patient the amplitude of ST displacement varied between episodes, presumably because of variation in the intensity of ischemia, but the QRS changes were directionally similar in each episode. In two patients there was also a smaller change involving the initial 40 msec of the QRS that could be represented by a vector directed away from the ischemic zone. To determine the possible mechanism for the electrocardiographic changes, ischemic episodes of 120 to 150 sec were produced in seven dogs and electrocardiographic recording and analysis techniques similar to those used in patients were employed. Myocardial conduction velocity was measured in three directions in the ischemic zone and was correlated with simultaneous electrocardiographic recordings from the body surface. The electrocardiographic changes in the dog preparation were virtually identical to those in the patients and strongly correlated with a fall in myocardial conduction velocity. We conclude that the QRS changes during variant angina result from the altered excitation pattern produced by conduction delay in the ischemic zone. The probable cause for the increase in terminal QRS voltage is delayed (and uncanceled) activation of the ischemic zone.Circulation 71, No. 5, 901-911, 1985. WE HAVE investigated the QRS changes during spontaneous ischemia in patients with variant angina by performing a detailed analysis of electrocardiograms from orthogonal leads. To

The authors have previously shown that 40% of patients whose ventricular arrhythmias respond to propranolol require plasma concentrations in excess of those producing substantial beta-receptor blockade (greater than 150 ng/ml). However, the electrophysiologic actions of propranolol have only been examined in human beings after small intravenous doses achieving concentrations of less than 100 ng/ml. In this study, the electrophysiologic effects of a wider concentration range of propranolol was examined in nine patients. Using a series of loading and maintenance infusions, measurements were made at baseline, at low mean plasma propranolol concentrations (104 +/- 17 ng/ml) and at high concentrations (472 +/- 68 ng/ml). Significant (p less than 0.05) increases in AH interval and sinus cycle length were seen at low concentrations of propranolol, with no further prolongation at the high concentrations; these effects are typical of those produced by beta-blockade. However, progressive shortening of the endocardial monophasic action potential duration and QTc interval were seen over the entire concentration range tested (p less than 0.05). At high concentrations, there was significant (p less than 0.05) further shortening of both the QTc and monophasic action potential duration beyond that seen at low propranolol concentrations, along with a progressive increase in the ratio of the ventricular effective refractory period to monophasic action potential duration. No significant changes were seen in HV interval, QRS duration or ventricular effective refractory period. In summary, the concentration-response relations for atrioventricular conductivity and sinus node automaticity were flat above concentrations of 150 ng/ml.(ABSTRACT TRUNCATED AT 250 WORDS)

No abstract

Differences between the electrophysiologic actions of the antiarrhythmic agent encainide have been reported after short-term intravenous and oral administration. Only prolongation of the HV interval and QRS duration have been described immediately after short-term intravenous administration of encainide in dogs and man. However, during oral therapy or more prolonged infusions, prolongation of the AH interval and atrial and ventricular effective refractory periods have also occurred. In most patients receiving encainide therapy, metabolites (O-demethyl encainide and 3-methoxy-0-demethyl encainide) accumulate during prolonged therapy to concentrations greater than those of the parent drug. We compared the electrophysiologic action of 0-demethyl encainide with that of saline in anesthetized dogs to determine if this metabolite has pharmacologic activity and whether its electrophysiologic effects could account for the disparities noted between effects of intravenous and oral encainide therapy. An initial pharmacokinetic evaluation allowed design of a series of loading and maintenance infusions that produced plasma concentrations similar to those seen during encainide therapy in man (concentration after first maintenance dose, 149 + 27 ng/ml [A+ SE] and after second maintenance dose, 230 + 45 ng/ml). Significant increases in atrial effective refractory period and ventricular refractoriness, and prolongation of AH interval and HV conduction time were observed. These effects are similar to those reported after prolonged oral encainide therapy but are substantially different from those seen after short-term infusions of encainide. These findings indicate that the difference between the electrophysiologic actions of intravenous and oral encainide may be due to pharmacologic effects of at least one encainide metabolite, 0-demethyl encainide. Circulation 68, No. 2, 385-391, 1983. ENCAINIDE is an investigational antiarrhythmic agent that has been found to be effective in the treatment of ventricular arrhythmias.' 6 Differences have been noted between the electrophysiologic actions of encainide observed immediately after an intravenous infusion and those during long-term oral therapy.

Ventricular fibrillation threshold (VFT), frequently determined in dogs during pentobarbital sodium anesthesia, usually is replaced by a single repetitive extrasystole threshold (SRET) or a multiple repetitive extrasystole threshold (MRET) determination in conscious animals and in the human being. In the present study SRET, MRET, and VFT were determined initially in 39 pentobarbital sodium-anesthetized dogs. One week later these three thresholds were redetermined during anesthesia in 13 of the 39 dogs (control group). In the remaining 26 dogs (experimental group), thresholds were redetermined while the dogs were conscious. Significant changes in threshold values occurred only in the experimental group for VFT (P < 0.001) and MRET (P < 0.02). The square of the linear correlation coefficient showed conscious state MRET to be a good predictor of conscious state VFT (R2 = 0.90). Conscious state SRET and anesthetized state VFT showed less predictiveness for the conscious VFT (R2 = 0.72 and 0.51, respectively). These data indicate that MRET may be preferable to SRET as an index of VFT. The SRET, MRET, and VFT determined during pentobarbital anesthesia may not accurately reflect the value of these parameters in the conscious animal.

No abstract

No abstract

No abstract