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Biomedical subjects

R A Winkle

Publications and source records attributed to R A Winkle.

At least 127 records · Page 7Linked to original sources
PubMed1977

Characteristics of ventricular tachycardia in ambulatory patients.

This study analyzes 94 episodes of the ventricular tachycardia recorded in the ambulatory electrocardiograms of 23 patients with stable cardiac disease. The episodes were asymptomatic in 19 patients, and only one episode resulted in ventricular fibrillation. Eighty-five percent of the episodes occurred when the underlying heart rate was less than 100 beats/min, and 17 percent occurred during sleep. The rate of the ventricular tachycardia was between 120 and 180 beats/min in 78 percent of the episodes and showed a modest correlation with the underlying heart rate (r = 0.59, P less than 0.001). Only 14 of the 94 episodes were initiated by R on T premature ventricular contractions, and the mean prematurity index (+/- standard deviation) (R-R'/Q-T) for all episodes was 1.31 +/- 0.28. Episodes of ventricular tachycardia recorded during ambulatory electrocardiographic monitoring are usually self-limited and asymptomatic. They occur during ordinary nonexertional activity and are frequently initiated by late couples premature ventricular contractions.

Ambulatory Care↗
PubMed1977

Acebutolol metabolite plasma concentration during chronic oral therapy.

1 We have measured the plasma concentration of acebutolol and a major metabolite in patients on chronic oral therapy with this drug, using a new assay, specific for each species. Our study suggests: 2 The acetyl metabolite was present in concentrations greater than those of acebutolol at all times during the dosing interval in all seven subjects. 3 The ratio of the mean steady-state plasma concentrations of the acetyl metabolite to unchanged acebutolol was 2.7 +/- 1.0. 4 Previous studies using non-specific methods that measure plasma concentrations of the acetyl metabolite and acebutolol as a single species cannot be used to determine pharmacokinetic parameters or to provide reliable correlations of plasma drug concentration with effect. 5 Future studies determining plasma concentration of acebutolol should take this metabolite into account. 6 Further work will be necessary to determine the metabolite's contribution to acebutolol's effects in man.

Acebutolol↗
PubMed1977

Suppression of premature ventricular contractions by acebutolol.

The antiarrhythmic action of the beta-blocking drug, acebutolol, was evaluated in patients with frequent premature ventricular contractions (PVCs). In the 12 hours following administration of a single 300 mg oral dose, 8 of 10 patients showed a greater than 50% reduction in PVC frequency, and statistical analysis indicated that PVC reduction persisted for 10 hours after the single dose. Analysis of plasma concentrations of acebutolol and an acetyl metabolite indicated that after single oral doses of plasma concentrations of the metabolite exceed those of unchanged acebutolol. When patients were studied during periods of 300 mg doses every 8 hours, eight of 11 showed a 70% reduction in PVC frequency, and analysis showed that the therapeutic effect was present throughout the 24-hour monitoring period. Acebutolol slowed the heart rate and prolonged the PR interval without affecting the QT interval. Significant clinical or laboratory toxicity was not encountered. In the small group studied, acebutolol was found to be safe and effective for short-term administration to patients with frequent PVCs and possessed a relatively long duration of antiarrhythmic action.

Acebutolol↗
PubMed1977

Surgical management of life-threatening ventricular arrhythmias in patients with coronary artery disease.

Twenty-one patients with coronary artery disease and severe, symptomatic ventricular arrhythmias underwent cardiac surgery after failure of medical managememt. All had coronary artery disease and either localized areas of severe hypokinesis (three patients), or ventricular aneurysms (18 patients) documented angiographically prior to surgery. Operation within one month after acute infarction resulted in an 80% in-hospital mortality, whereas operation more than one month postinfarction showed a 20% mortality. Operative treatment that included myocardial resection had a significantly lower mortality (P less than 0.05) than that which did not. With an average of 36.5 months of follow-up, 13 of the 21 patients were long-term survivors, despite the persistence of ventricular arrhythmias. Surgical treatment which includes myocardial resection and occurs more than one month after infarction should be considered in patients with symptomatic ventricular arrhythmias and severe, well-localized left ventricular wall motion abnormalities.

Adult↗
PubMed1977

The electrophysiologic effects of quinidine in the transplanted human heart.

Using His bundle recording techniques, we examined direct and autonomically mediated conduction system effects of quinidine in five cardiac transplant recipients who have anatomically denervated hearts. We made control conduction interval and refractory period measurements, and then infused 10 mg/kg quinidine gluconate over a 20-min period. At 30 min, we determined the electrophysiologic changes induced by quinidine. Quinidine significantly increased the atrial-His (AH) interval (from 97+/-9 [SEM] to 108+/-7 ms, P less than 0.001), the His-ventricular (HV) inteval (from 43.9 +/- 1 to 52.8 +/- 3 ms, P less than 0.01), the donor heart sinus cycle length (from 599 +/- 38 to 630 +/- 56 ms, P less than 0.08), and the atrial effective refractory period (from 214 +/- 14 to 241 +/- 11 ms, P less than 0.01). Quinidine significantly decreased the innervated, remnant atrial sinus cycle length (from 847 +/- 104 to 660 +/- 96 ms, P less than 0.01) and the blood pressure. The mean plasma concentration of quinidine at the time that electrophysiologic measurements were repeated was 4.37 +/- 0.449 micrograms/ml. We conclude that quinidine's predominant sinus nodal and atrioventricular nodal effects in man are autonomically mediated and opposite to its direct actions upon these structures. On the other hand, quinidine's prevailing effect on atrial refractoriness and His-Purkinje conduction in man is direct.

Blood Pressure↗
PubMed1977

Benign slow paroxysmal atrial tachycardia.

Review of 203 24-h ambulatory electrocardiographic tapes of 140 patients disclosed 32 patients with 66 episodes of paroxysmal atrial tachycardia. In contrast to classic sustained paroxysmal supraventricular tachycardia, these episodes were relatively slow and brief. The median duration was 7 beats and the mean 116 beats/min. All episodes were asymptomatic except for three prolonged paroxysms that produced mild palpitation. Sixty-eight percent (45/66) of these episodes occurred during sleep or sinus bradycardia. This was the most common paroxysmal supraventricular arrhythmia observed, and it occurred in patients with a wide variety of cardiac diagnoses. The majority of these episodes appear to arise from an atrial ectopic origin. We conclude that these brief slow atrial paroxysms represent a benign arrhythmia. This rhythm disturbance is present in as many as one quarter of cardiac patients undergoing ambulatory electrocardiographic monitoring. It should not be confused clinically with classic sustained paroxysmal supraventricular tachycardia.

Adult↗
PubMed1976

Life-threatening arrhythmias in the mitral valve prolapse syndrome.

This study describes seven patients with the mitral valve prolapse or click-murmur syndrome who have survived one or more episodes of life-threatening ventricular arrhythmias. These arrhythmias include cardiac arrest due to ventricular fibrillation, recurrent ventricular tachycardia causing syncope or sustained ventricular tachycardia requiring electroversion. These patients were seen over a two-year period in a single medical center. Five of the seven had repolarization abnormalities in the resting electrocardiogram. Premature ventricular contractions were present in the routine resting electrocardiograms of six of the seven patients and were frequent during treadmill testing and ambulatory electrocardiographic monitoring in all six tested. There were electrolyte abnormalities or changes in medications known to affect myocardial repolarization during the week before the episode in three of the four patients with cardiac arrest. The diagnosis of mitral valve prolapse click-murmur syndrome was made prior to the episode of life-threatening arrhythmia in only two of the seven patients. Varying forms of antiarrhythmic therapy were given to these patients during follow-up periods of five to 26 months. Although the incidence of fatal arrhythmias in the mitral prolapse syndrome is probably small, we suggest that such arrhythmias may not be extremely rare, particularly among those patients who have repolarization abnormalities in the resting electrocardiogram and frequent premature beats. Patients with unexplained ventricular arrhythmias should be screened for mitral valve prolapse.

Adult↗
PubMed1976

Echocardiographic evaluation of propranolol therapy for mitral valve prolapse.

This study evaluates the effect of propranolol on the echocardiogram of 8 patients with late systolic mitral value prolapse. Echocardiograms were performed with the patients on no medication and again while on oral propranolol therapy. Propranolol caused a statistically significant increase in left ventricular volume; however, neither the echocardiographic pattern nor the timing of mitral valve prolapse was altered by propranolol. These findings suggest that factors in addition to left ventricular volume play a role in regulating valvular dysfunction in this condition.

Cardiac Volume↗
PubMed1976

Clinical efficacy and pharmacokinetics of a new orally effective antiarrhythmic, tocainide.

Tocainide, a new oral antiarrhythmic agent, was studied in man in a short-term protocol designed to evaluate the efficacy, kinetics, and toxicity of this compound. Premature ventricular contractions (PVCs) were suppressed by less than 70% in 11 of 15 patients compared with pre-drug placebo controls. For these 11 responders, there was an average PVC reduction of 91% +/- 10 (range 70 to 100%) at tocainide doses not associated with side effects. Mild transient central nervous system toxicity was observed in some patients near the time of peak concentrations during the highest dose administered. The drug was found to have linear kinetics over the dose range studied and a plasma half-life of 13.5 +/- 2 hours. Plasma concentration-response curves indicate antiarrhythmic activity over all plasma concentrations, with 70% PVC reduction above 6.0 mug/ml. This study suggests that tocainide is a safe and effective antiarrhythmic agent during short-term administration and is worthy of further clinical trials.

Administration, Oral↗
PubMed1976

Treatment of recurrent symptomatic ventricular tachycardia.

Eleven consecutive patients with recurrent ventricular arrhythmias were treated by an aggressive protocol and followed up prospectively. Arrhythmias, symptoms, and cardiac lesions were defined. Antiarrhythmic drugs were given on schedule, with blood levels determining dose; success or failure was defined by elimination or recurrence of symptomatic arrhythmias. When drug therapy failed, left ventricular aneurysmectomy was done when appropriate. Recurrent ventricular tachycardia was most frequently responsible for symptoms; coronary artery disease was the most frequent underlying disease. Symptomatic arrhythmias were eliminated in 8 of 11 patients (5 with drugs and 3 with aneurysmectomies), with a 16.5-month symptom-free average follow-up. An average of 2.9 therapeutic trials per patient was needed to control symptomatic arrhythmias. The average time from entry into the study until the start of ultimately effective therapy was 18 days. Therapy that eliminated symptoms did not eliminate all premature ventricular contractions, and occasionally even brief asymptomatic episodes of ventricular tachycardia persisted. Recurrent symptomatic ventricular arrhythmias can be controlled in many patients by rigorous application of current therapies.

Adult↗
PubMed1975

Pharmacologic therapy of ventricular arrhythmias.

To treat patients with ventricular arrhythmias properly, one must characterize the arrhythmia, define the underlying heart disease and look for and treat reversible causes. When arrhythmias are suitable for pharmacologic suppression, it is necessary to predefine therapeutic goals, then carefully document that the drug accomplishes these goals. Knowledge of a drug's metabolism, excretion, active metabolites and plasma protein binding is often required for full understanding of its clinical effect. Pharmacokinetic principles require that antiarrhythmic drugs be given on a rigid schedule and that plasma drug levels be frequently determined. Use of compartment models and the principle of superposition can enable one to achieve and maintain therapeutic drug concentrations while avoiding toxic side effects. The drugs commonly used to treat arrhythmias, lidocaine, propranolol, procainamide, diphenylhydantoin and quinidine, as well as some newer agents, have specific pharmacokinetics and toxic effects that must be understood.

Anti-Arrhythmia Agents↗
PubMed1975

Pharmacokinetics and metabolism of lidocaine in patients with renal failure.

The kinetics of distribution and elimination of lidocaine and two of its metabolites, monoethylglycinexylidide (MEGX) and glycinexylidide (GX), were studied in 4 uremic patients on chronic hemodialysis. Each patient received a loading dose of 75 mg of lidocaine, followed by a 30 mug/kh/min lidocaine infusion. No toxic side effects from lidocaine were seen during the study. Average values for lidocaine steady-state plasma levels (2.3 mug/ml) clearance (12.3 ml/min/kg), terminal half-life (148 min), and total volume of distribution (1.9 L/kg) were found, and are similar to those values reported for normal subjects MFGX and after lidocaine infusion averaged 1/5-2/3 of the corresponding lidocaine level, as in nonuremic subjects, and plateaued by 6-8 hr. GX levels did not reach plateau by 12 hr and remained relatively unchanged after infusion. It is concluded that lidocaine infusion in uremic patients is safe, with no abnormal cumulation of lidocaine or MEGX. GX levels, however, may increase progressively, even after 12 hr.

Computers↗
PubMed1975

Simultaneous echocardiographic phonocardiographic recordings at rest and during amyl nitrite administration in patients with mitral valve prolapse.

Simultaneous electrocardiograms, phonocardiograms, and echocardiograms were recorded in 21 patients with mitral valve prolapse. Four patients with holosystolic mitral valve prolapse on echocardiogram had smaller resting end-diastolic volumes than the remaining 17 patients with late systolic echocardiopraphy prolapse (p greater than 0.01). Thirteen of the 17 patients with late systolic prolapse had phonocardiograhically recorded auscultatory phenomena. The initial vibrations of the auscultatory phenomena occurred after the onset of echocardiographic prolapse, but prior to maximal echocardiographic mitral valve prolapse. Amyl nitrite was administered to all patients. Three of the 17 patients with late systolic prolapse developed holosystolic prolapse, while the remaining 14 retained the late systolic prolapse pattern during amyl nitrite inhalation. In these 14 patients, the onset of mitral prolapse occurred earlier in systole due to decrease in the duration of systole prior to onset of mitral valve prolapse (p greater than 0.001). This corresponded with the occurrence of auscultatory phenomena earlier in systole. Twelve patients had left ventricular volumes recorded during amyl nitrite inhalation and all showed a decrease in left ventricular volumes (greater than) 0.001). These findings confirm the temporal relationship of mitral valve prolapse and onset of auscultatory phenomena in these patients. It suggests that the movement of auscultatory phenomena earlier in systole during amyl nitrite inhalation is related to earlier prolapse of the mitral valve, and that a decrease in ventricular valume is a tenable explanation for the earlier onset of prolapse.

Administration, Intranasal↗
PubMed1975

Arrhythmias in patients with mitral valve prolapse.

Resting ECGs, exercise treadmill tests and 24-hour ambulatory ECGs were recorded and analyzed in 24 unselected patients with mitral valve prolapse. Arrhythmias were frequent. There were three distinct groups of patients, defined on the basis of total number of premature ventricular contractions (PVCs) during the 24 hours; there were no PVCs in 25%, and frequent PVCs in 50%. Complex ventricular arrhythmias, including ventricular tachycardia in five patients, were found almost exclusively in the group with frequent PVCs. Fifteen of the 24 patients demonstrated atrial premature contractions (APCs) during the 24 hours. Complex atrial arrhythmias were found among patients with infrequent, as well as those with frequent, APCs. Supraventricular tachycardia was detected in seven of these patients. The incidence of ACPs decreased during sleep in 67% of the patients and showed no change during sleep in 33%. A poor correlation was found between symptoms recorded in patient diaries and changes noted on 24-hour ECG recordings. The peak PVCs/15 min and peak ACPs/15 min during a 24-hour period of monitoring was found to be an excellent guide to the total number of PVCs and APCs occurring during that period. This permits an accurate prediction of the total number of PVCs in 24 hours after performing an exact PVC count on only 15 minutes of ECG data. Finally, the 24-hour ambulatory ECG was sensitive than the treadmill test and both were superior to the 12-lead ECG for detecting arrhythmias in these patients.

Adult↗
PubMed1975

The status of cardiac transplantation, 1975.

Since December 1967, 263 human cardiac transplant operations have been performed throughout the world. Eighty-two of these were performed at Stanford University Medical Center, In 1974, 27 such operations were performed, 15 at Stanford Survival rates for the entire Standford series are 48% at one year and 25% at three years; survival rates at one and three years for patients surviving the first three critical months after transplantation are 77% and 42%, respectively. Recipients under the age of 55 years, with New York Heart Association Class IV cardiac disability, are selected for transplant procedures according to criteria dictated by experience over the past seven years. A routine immunsuppressive regimen for organ transplantation, incorporating prednisone, azathioprine, and antithymocyte globulin is employed early postoperatively, and prednisone and azathioprine are used for indefinite maintenance therapy. Acute cardiac graft rejection in nearly all recipients is diagnosed by clinical signs, electrocardiographic changes, and percutaneous transvenous endomyocardial biopsy. Ninety-five percent of acute rejection episodes are reversible with appropriate immunosuppressive treatment, but infectious complications are common and have accounted for 56% of all postoperative deaths. The Stanford experience in cardiac transplantation has demonstrated the potential therapeutic value of this procedure. Maximum survival now extends beyond five years. Satisfactory graft function has been documented in long-term surviving patients, the majority of whom have enjoyed a high degree of social and physical rehabilitation.

Acute Disease↗