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Biomedical subjects

R A Winkle

Publications and source records attributed to R A Winkle.

134 records · Page 8Linked to original sources
PubMedDate not supplied

Patterns of cognitive recovery in sudden cardiac arrest survivors: the pilot study.

OBJECTIVE: To determine the prevalence, type, severity, and natural evolution of cognitive impairments in survivors of sudden cardiac arrest over time and to assess the relation of selected clinical and psychologic variables to those outcomes. DESIGN: Longitudinal with repeated measures. Twenty-five consecutive patients underwent extensive neuropsychologic testing during hospitalization within 3 weeks of their initial cardiac arrest. Of these, 17 completed additional testing at 6 to 9 weeks, 12 to 15 weeks, and 22 to 25 weeks after the event. SETTING: Cardiac electrophysiologic services at a university teaching hospital, a community hospital, and home. OUTCOME VARIABLES: Orientation, attention, concentration, immediate recall, early retention, delayed recall, reasoning, motor speed, and motor regularity were measured. RESULTS: During hospitalization, 72% of the patients had mild to severe impairments in one or more cognitive areas. Memory, particularly delayed recall, was the most common deficit. At 6 months after the arrest event, 29% (5 of 17) of the patients continued to be impaired, and all had deficits in delayed recall. Depression was significantly related to deficits in attention and delayed recall at 6 months only. Time to postarrest awakening was the most reliable predictor of long-term cognitive functioning in this patient sample. CONCLUSION: A significant minority of sudden death survivors incur long-term cognitive impairments, particularly in delayed recall or short-term memory. The occurrence of long-term cognitive deficits in these patients can be estimated from the duration of unconsciousness after resuscitation (time-to-awakening).

Adult↗
PubMedDate not supplied

Effects of encainide (MJ9067) on the ventricular fibrillation threshold in anesthetized dogs.

The right ventricular epicardial ventricular fibrillation threshold (VFT) was determined during paced supraventricular rhythm using 100 Hz trains of stimuli at 15 min intervals in dogs before and during the intravenous administration of encainide, a new antiarrhythmic drug. With each VFT determination, simultaneous blood samples were obtained for determination of drug concentration. In 6 control dogs, VFT determined every 15 min during a 210 administered as a 90 min intravenous infusion at three successive rates (0.01, 0.02 and 0.04 mg/kg/min) for 30 min each. VFT measured at 5 and 20 min of each infusion increased from a mean control of 11.5 +/- 1.5 (+/-SE) to 20.2 +/- 2.2 mA (p less than 0.01) after 20 min of the third infusion. The maximal effect occurred during the second infusion with plasma concentration of 594 +/- 46 ng/ml and then reached a plateau. In group II (n = 6), encainide was administered in four successive sequences, each one including a bolus loading intravenous dose followed by a 45 min intravenous infusion. VFT measured at 30 and 45 min of each infusion when the encainide plasma concentration was close to a steady state increased significantly (p less than 0.01) after the second infusion from 11.8 +/- 2 to 27.3 +/- 4 mA. Two dogs in group II developed transient complete atrioventricular block at an encainide plasma concentration of greater than 800 ng/ml. These results show that the new antiarrhythmic drug encainide increases the VFT in anesthetized dogs.

Anesthesia↗
PubMedDate not supplied

Comparative electrophysiology of lorcainide and norlorcainide in the dog.

Electrophysiologic effects of intravenous lorcainide and its major metabolite, norlorcainide, were examined in 18 anesthetized dogs, using intracardiac electrophysiologic measurements and programmed stimulation. Lorcainide and norlorcainide were studied separately, using six dogs for each experiment. Each compound was administered by a series of 5 one-h graded infusions each involving a loading dose over 15 min followed by a 45-min maintenance infusion. Plasma concentrations ranged from 94 +/- 34 to 1345 +/- 471 ng/ml for lorcainide and 81 +/- 22 to 1344 +/- 458 ng/ml for norlorcainide. Six additional dogs were studied, using a combination of a constant lorcainide infusion and four progressively increasing doses of norlorcainide. Both lorcainide and norlorcainide caused concentration-dependent prolongation of PR interval, QRS duration, AH and HV intervals, atrial and ventricular effective refractory periods, and the atrioventricular nodal functional refractory period. For each electrophysiologic parameter, plots of percent change as a function of log plasma concentration were nearly superimposable for lorcainide and norlorcainide. Plots for the combined treatment group using the total plasma concentration of lorcainide and norlorcainide were similar to those for each compound alone. We conclude that in dogs norlorcainide has considerable electrophysiologic activity, and is approximately equieffective and equipotent when compared with lorcainide, and that the electrophysiologic effects of the two compounds appear additive.

Animals↗
PubMedDate not supplied

Pharmacokinetics of oral cibenzoline in arrhythmia patients.

The pharmacokinetics of oral cibenzoline were studied in 30 arrhythmia patients as part of an ascending multiple-dose efficacy study. The elimination half-life of the drug following repetitive dosing ranged from 7.6 to 22.3 hours, with a harmonic mean of 12.3 hours (n = 24), and increased with age and decreasing renal function. The drug exhibited apparent dose proportional and linear pharmacokinetics over the range of doses studied. Multivariate analysis revealed that the patients' age and serum creatinine concentration accounted for 71% of the variability in the range of beta values (terminal elimination rate constant), and that 69.5% of the intersubject variability in the steady-state trough plasma concentrations could be accounted for by the patients' age, weight and serum creatinine concentration. These data suggest that, although there is some intersubject variability in the elimination and accumulation of cibenzoline, much of the variability can be explained by the patients' age, weight and renal function.

Administration, Oral↗
PubMedDate not supplied

Monitoring electrocardiographic data in ambulatory patients.

Sustained periods of extremely rapid or slow heart rate or initiation of the heartbeat from an ectopic focus can lead to serious clinical impairment or even death. Because disturbances of cardiac rhythm are ofter intermittent and evanescent, the development of systems for recording electrocardiograms in ambulatory patients for later analysis has been of clinical utility in diverse forms of heart disease. The basic components of such systems include a compact portable tape recorder for recording electrocardiographic data and a playback system with facilities for data analysis. Recently, semi-automated, computer-assisted analysis of this electrocardiographic data and quantitative analysis of the frequency of abnormal rhythms have become possible. In addition to widespread application for diagnostic purposes, ambulatory electrocardiographic techniques are now being used to evaluate new drugs for the treatment of cardiac rhythm disturbances and to define subsets of cardiac patients in whom treatment of rhythm disturbances may be desirable.

Ambulatory Care↗