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Biomedical subjects

R A Winkle

Publications and source records attributed to R A Winkle.

At least 91 records · Page 5Linked to original sources
PubMed1982

The relationship between ventricular ectopic beat frequency and heart rate.

We examined the relationship between the frequency of premature ventricle complexes (PVCs) and underlying heart rate in 24 patients with frequent PVCs using 24-hour ambulatory ECG recordings. Plots of PVC frequency vs heart rate were made at 1-beat/min intervals for all heart rates that were recorded for at least 5 minutes of the 24 hours. Heart rates during 24 hours ranged from 56 +/- 10.0 to 102.2 +/- 15.4 beats/min. Twenty-three of the 24 patients had a distinct relationship between PVC frequency and heart rate. Patterns included an approximate log-linear increase in PVCs at higher heart rates in 12 patients, a log-linear decrease (overdrive suppression) in one patient, flat curves in three patients, and a complex relationship (e.g., more PVCs at low rates and suppression at high rates) in seven patients. Patterns were reproducible in 21 of the 24 patients on repeat ambulatory ECG monitorings done 1 day to 2 months later. We conclude that most patients with frequent PVCs have a characteristic relationship between PVC frequency and heart rate over the range of heart rates achieved during routine daily activity. The most frequent relationship is a marked increase in PVC frequency with increasing heart rate. These observations may in part explain such phenomena as "spontaneous" variability of PVC frequency, sleep suppression of PVCs and suppression of PVCs by beta-blocking drugs.

Adult↗
PubMed1982

Antiarrhythmic drug combinations in the treatment of ventricular tachycardia.

Combinations of antiarrhythmic drugs are frequently used to treat refractory ventricular tachycardia (VT), but few scientific data support this practice. We examined the efficacy and electrophysiology of 110 antiarrhythmic drug combination trials at electrophysiologic study in 74 patients with recurrent ventricular tachycardia. Lidocaine was combined with quinidine in 33 trials, procainamide in 22 and encainide in 20. Propranolol was combined with quinidine in 17 trials, procainamide in 12 and encainide in six. All individual drugs tested (except propranolol, which was usually not tested individually) had failed at electrophysiologic study or clinically in the presence of usually accepted plasma concentrations. Lidocaine in combination with quinidine was effective in 3% of the trials, with procanamide in 5% and with encainide in none of the trials. Propranolol in combination with quinidine was effective in 18% of the trials, with procainamide in 17% and with encainide in none of the trials. The electrophysiologic effects of the tested drug combinations were dominated by the individual effects of the type 1 antiarrhythmic agents. We conclude that the tested antiarrhythmic drug combinations are infrequently effective in preventing VT induction at electrophysiologic study when each agent has failed individually. The addition of lidocaine or propranolol to quinidine, procainamide or encainide does not produce significant synergistic or new effects on the electrophysiologic variables analyzed.

Aged↗
PubMed1981

Malignant ventricular tachyarrhythmias associated with the use of encainide.

In patients treated with the antiarrhythmic drug, encainide, the agent appeared to cause or exacerbate malignant ventricular tachyarrhythmias in 11 cases. The most common type of arrhythmia associated with encainide toxicity was polymorphic ventricular tachycardia (VT) resulting in cardiac arrest. In contrast to drug-induced arrhythmias commonly encountered with quinidine and other type I antiarrhythmic drugs, encainide-induced rhythm was not associated with marked QT prolongation, was not necessarily initiated by R-on-T premature ventricular beats, and usually did not self-terminate. Two patients could not be resuscitated from the rhythm, and several others required prolonged or multiple resuscitations. The risk of encainide-induced ventricular tachyarrhythmias was 11% in 90 patients receiving the drug for recurrent sustained VT and/or fibrillation (VF), 2.2% in 47 patients receiving the drug for chronic complex ventricular ectopic activity. Encainide-induced arrhythmias occurred 29.8 +/- 11.3 hours (range 17 to 48 hours) after starting chronic oral maintenance doses or after dose increases, or 1 to 2 hours after single large doses. Patients experiencing this adverse effect could not be distinguished from those who did not on the basis of encainide dose, degree of QRS widening, or clinical status. We recommend that patients with history of sustained VT or VF have encainide therapy started only in a hospital setting with continuous ECG monitoring and capabilities for cardiopulmonary resuscitation. Dose changes should not be made more frequently than every 48 hours, and patients should not be discharged from the hospital until they have been on stable dose of encainide for a minimum of 48 hours.

Adult↗
PubMed1981

Electrophysiologic effects of N-acetylprocainamide in human beings.

The electrophysiologic properties of N-acetylprocainamide (NAPA) were studied in 10 patients undergoing cardiac catheterization. Each patient received two successive intravenous infusions: one loading infusion over 15 minutes and one maintenance infusion at a slower rate for 30 minutes. Eight patients received 10.5 mg/kg body weight and two received larger doses (16 and 21 mg/kg, respectively). NAPA plasma concentration was measured at 5 minute intervals from 0 to 25 minutes, and then at 15 and 30 minutes of the second infusion. Mean blood pressure and electrophysiologic data obtained by programmed stimulation were recorded before drug administration and at 15 and 30 minutes of the infusion when the concentration of NAPA was nearly constant in each patient (range 12 to 35 microgram/ml). NAPA decreased blood pressure (p less than 0.005), increased corrected Q-T interval (p less than 0.01) and increased the atrial and ventricular effective refractory periods from 267 +/- 40 to 307 +/- 41 ms (p less than 0.01) and from 278 +/- 37 to 301 +/- 32.8 ms (p less than 0.05), respectively. NAPA did not significantly change sinus cycle length or sinus nodal recovery time, conduction intervals (A-H, H-V, P-R, QRS), atrioventricular nodal functional refractory period or nodal Wenckebach cycle length. The patient receiving the largest dose experienced mild nausea when the plasma concentration was above 35 microgram/ml. These data show that the electrophysiology of NAPA in human beings is different from that reported for procainamide. At the plasma concentrations studied NAPA increases atrial and ventricular refractory periods without increasing cardiac conduction times

Acecainide↗
PubMed1981

Clinical pharmacology and antiarrhythmic efficacy of N-acetylprocainamide.

Eleven patients with chronic ventricular arrhythmias took part in a study of N-acetylprocainamide (NAPA), the major metabolite of procainamide, in order to characterize further NAPA's clinical pharmacology and antiarrhythmic action. The frequency of ventricular arrhythmia on 24 hour ambulatory electrocardiographic recordings was comparable on recordings obtained in a prestudy screening, during treatment with placebo before administration of NAPA and after treatment with NAPA. The initial dosage of NAPA was 500 mg every 8 hours, which was increased by 500 mg increments every few days until 90 percent suppression of arrhythmia or intolerable adverse effects occurred. Only two patients achieved 90 percent suppression of ventricular ectopic complexes. The mean plasma concentration associated with 90 percent suppression of arrhythmia in these two patients ws 12.6 and 32.3 mg/ml, respectively. One of these two patients was unable to continue long-term therapy with NAPA because of a rash. Other adverse effects included gastrointestinal symptoms in seven patients with visual symptoms in four patients at plasma concentratons as low as 6.9 mg/ml. NAPA obeyed linear pharmacokinetics over the range of dosages studied (500 to 2,500 mg every 8 hours) and had a half-life of 10.7 +/- 1.98 hours (mean +/- standard deviation). There was no change in the P-R or QRS intervals and there was a dose-dependent prolongation of the Q-Tc interval. It is concluded that in this patient group, NAPA suppressed chronic ventricular ectopic complexes without adverse effects in only a minority of patients.

Acecainide↗
PubMed1981

Myocardial involvement in idiopathic hemochromatosis. Morphologic and clinical improvement following venesection.

We describe a 31 year old male patient who presented with severe cardiomyopathy caused by primary hemochromatosis. After a stormy course, complicated by heart failure and severe ventricular arrythmias, improvement in clinical status and myocardial function occurred. Depletion of myocardial iron was documented by the technique of serial endomyocardial biopsy. Myocardial iron stores were not yet depleted when hypoferremia and iron deficiency anemia occurred. This is the first reported study of myocardial morphology in a successfully treated patient with hemochromatotic cardiomyopathy.

Adult↗
PubMed1981

Characterization of ventricular tachyarrhythmias on ambulatory ECG recordings in post-myocardial infarction patients: arrhythmia detection and duration of recording, relationship between arrhythmia frequency and complexity, and day-to-day reproducibility.

We performed three consecutive 24-hour ECG recordings in 57 ambulatory patients approximately 8 to 11 days of post-myocardial infarction. There was considerable additional detection of each type of complex ventricular ectopic beat (VEB) with recordings beyond 24 hours. Multiform, R-on-T, pairs, and bigeminy were often first detected from 24 to 48 hours and 5 of 12 patients with ventricular tachycardia had this rhythm detected only after 48 hours of monitoring. Complex forms were deleted with short recording durations primarily in patients who had complex forms present during a large number of hours during the 72-hour recording session. The occurrence of each type of complex ectopic beat was strongly related to PVC frequency and some type of complex form was seen in virtually all 24-hour recordings with greater than a total of 100 VEBs. Sixty-five percent of 24-hour recordings with infrequent VEBs (2 to 10 per 24 hours) also had complex forms present. The day-to-day reproducibility of VEB frequency and complexity was reasonable, but was largely accounted for by the fact that most recordings were free of frequent ectopic beats and a given type of complex PVC. These data suggest that for longer ECG recording period, the frequency of occurrence of complex forms rather than simply their presence or absence may be important for identifying high risk subgroups.

Adult↗
PubMed1981

Clinical pharmacology and antiarrhythmic efficacy of encainide in patients with chronic ventricular arrhythmias.

We determined the pharmacokinetics, efficacy and therapeutic plasma concentration of encainide, a new antiarrhythmic drug that affects His-Purkinje conduction but not ventricular refractoriness. Nine patients with frequent and complex premature ventricular complexes were studied in a 3-day double-blind protocol. Each day, each patient received 75 mg of i.v. or oral encainide or placebo. Frequent blood samples for encainide plasma concentration determination and continuous ambulatory ECGs were obtained. There was a marked intersubject variation in bioavailability (mean 42 +/- 24%, range 7.4-82%), clearance (13.2 +/- 5.6 ml/min/kg, range 3.75-22.1 ml/min/kg) and half-life (3.4 +/- 1.7 hours i.v., 2.5 +/- 0.8 hours oral). Eight of nine patients had more than 90% suppression of premature ventricular complexes for 3-36 hours. Minimal antiarrhythmic plasma concentration was higher (39 +/- 54 ng/ml, range 3.5-170 ng/ml) after i.v. dosing than after oral dosing (14 +/- 16 ng/ml, range 1.5-48 ng/ml), suggesting an active metabolite after oral dosing in many patients. Minimal side effects were seen despite high peak plasma concentrations (range 794-1556 ng/ml i.v., 36-495 ng/ml oral). The minimal ratio of toxic to therapeutic plasma concentration ranged from 4.3-326 (median 23) after oral dosing. Antiarrhythmic action was associated with an 11-44% widening of the QRS complex that was not associated with other adverse effects. We conclude that encainide effectively suppresses ventricular arrhythmias. Despite a variable bioavailability, high clearance and short half-life, its wide ratio of toxic to therapeutic concentration and probable active metabolite permit a long duration of action, which should allow a reasonable dose schedule in most patients during chronic oral dosing.

Aged↗
PubMed1980

Accuracy of the ventricular tachycardia-induction study for predicting long-term efficacy and inefficacy of antiarrhythmic drugs.

We evaluated the prophylactic effect of antiarrhythmic agents against induction of ventricular tachycardia by extrastimulation in 51 patients with recurrent ventricular tachycardia. These patients subsequently underwent 58 long-term trials with tested agents. In 39 trials an agent predicted to be effective by electrophysiologic study was administered, and in 19 a drug predicted to be ineffective was used. There were no clinical differences between the two treatment groups. During a mean follow-up period of 8.2 months, arrhythmias recurred significantly less frequently in the group treated with drugs predicted to be effective than in the other group (P < 0.001); at six months 80 per cent of the patients in the former group were successfully treated, as compared with 33 per cent in the latter group. At 18 months the corresponding figures were 68 per cent and 11 per cent. We conclude that the arrhythmia-induction technique accurately predicts the clinical effectiveness of drugs used in the long-term treatment of recurrent ventricular tachycardia.

Adult↗
PubMed1980

Tocainide for drug-resistant ventricular arrhythmias: efficacy, side effects, and lidocaine responsiveness for predicting tocainide success.

Tocainide therapy has been evaluated in 38 patients with ventricular arrhythmias. Thirty-one had recurrent sustained ventricular tachycardia and/or fibrillation and 29 required prior cardioversions. These arrhythmias could not be managed with quinidine, procainamide, disopyramide, or propranolol. Tocainide doses averaged 1,500 mg/day (range 600 to 2,400) and the majority of patients had plasma concentrations from 6 to 12 micrograms/ml. Twenty-two patients (61%) had their arrhythmias controlled with tocainide and 16 (39%) did not. Tocainide dose and plasma concentrations were similar for responders and nonresponders. Lidocaine was effective in 26 patients and 16 (63%) of these had their arrhythmias controlled with tocainide. Of 12 patients in whom lidocaine was known to be ineffective or who had not been previously treated, only two (17%) had arrhythmias controlled with tocainide (P < 0.02). Side effects occurred in approximately two thirds of patients but required discontinuation of long-term tocainide in only three patients.

Aged↗
PubMed1980

Intravenous N-acetylprocainamide disposition kinetics in coronary artery disease.

N-Acetylprocainamide (NAPA) disposition kinetics was studied in eight patients with coronary artery disease. NAPA was given over a 45-min period by intravenous infusion, and blood samples were drawn at specified times for 24 hr. NAPA plasma levels were determined by a specific high-pressure liquid chromatography (HPLC) procedure and the concentration-time data were fit to a three-compartment model. Mean (+/- SD) values for the elimination half-life, the total body clearance, and the steady-state volume of distribution were 9.53 +/- 3.22 hr, 1.98 +/- 0.40 ml/min/kg, and 1.30 +/- 0.18 1/kg. There was moderate intersubject variability in disposition. The data reported here differ from those reported for normal subjects.

Acecainide↗
PubMed1980

Time dependency of ventricular fibrillation thresholds determined using trains of stimuli.

When determining ventricular fibrillation threshold (VFT), considerable time elapses from beginning a VFT measurement until the actual occurrence of ventricular fibrillaion (VF). We have defined this elapsed time as the "time to VF" and examined the effect of varying time to VF on the measured value of VFT. We induced VF in anesthetized dogs with a 100-Hz train of 16 4-ms stimuli applied to the right ventricular epicardium. The time to VF was varied by changing either the increment of fibrillation current increase (0.5, 1.0, or 2.0 mA) from one train to the next and/or the number of atrial paced beats between trains (6-192 beats). For 0.5-mA current increments, as time to VF increased from 66 to 454 s, VFT fell progressively from 15.3 +/- 4.8 to 6.7 +/- 1.1 mA. When time to VF exceeded 454 s, VFT increased again. Current increments of 1.0 and 2.0 mA had a similar time dependency of VFT. For any time to VF the VFT was lower when small current increments (i.e., more trains) were used to induce VF. Pretreatment with reserpine in six dogs abolished the time dependency. We conclude that time elapsed from the beginning of a VFT determination until VF actually occurs and the total number of trains used are important determinants of the VFT, probably because of local catecholamine release by the stimuli.

Animals↗