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Biomedical subjects

D C Harrison

Publications and source records attributed to D C Harrison.

427 records · Page 24Linked to original sources
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

The stereoselective disposition of disopyramide in the dog.

The disposition of d-, 1-, and d,1-disopyramide was studied in 5 conscious dogs after intravenous administration (15 mg/kg) of each compound using a balanced crossover design. The clearance of d-disopyramide (15.4 +/- 5.10 ml/min/kg) was significantly greater than that of the l-isomer (9.45 +/- 2.52 ml/min/kg) (p < 0.001). The clearance of the d,1-mixture was intermediate between that obtained for the d- and l-isomers. The steady-state volume of distribution of the three compounds was similar (approximately 1.4 liters/kg). The elimination half-life reflected differences in clearance, being 76.4 +/- 7.30 min for d-disopyramide, 112 +/- 23.4 min for 1-disopyramide, and 97.2 +/- 15.1 min for d,1-disopyramide. The effect of general anesthesia with urethane and chloralose on the disposition of the compounds was also examined. General anesthesia decreased the clearance and increased the half-life of all three compounds. No consistent differences in the volume of distribution were observed with anesthesia as compared to control. Thus, there is stereoselective elimination of the optical isomers of disopyramide in the dog, and general anesthesia decreases the clearance of d-, 1-, and d,1-disopyramide.

Anesthesia↗
PubMedDate not supplied

Effects of equipotent blocking doses of acebutolol, acebutolol's primary metabolite, and propranolol on left ventricular hemodynamics in conscious awake dogs.

In six conscious dogs we compared the hemodynamic effects of propranolol, acebutolol, and acebutolol's primary metabolite at equipotent beta-blocking doses. Aortic pressure, heart rate, left ventricular end-diastolic pressure, dP/dt, and aortic flow velocity were measured 3 weeks after sterile surgery during three infusions of each drug. Only one drug was given on each day. The equipotent beta-blocking dose of each drug was obtained by comparing isoproterenol dose-response curves. All three drugs produced a fall in dP/dt. Left ventricular end-diastolic pressure increased in most dogs, but this was only significant for acebutolol. The heart rate tended to fall and the blood pressure rise, but this was variable and not significant. The concentration of the equipotent blocking dose of acebutolol was 44 times that of propranolol, and while the concentration of acebutolol's metabolite was 1.6 times that of acebutolol. In conclusion, at a concentration similar to acebutolol, acebutolol's metabolite has heart rate blocking and myocardial depressive effects similar to those of propranolol and acebutolol.

Acebutolol↗
PubMedDate not supplied

Electrophysiology of the enantiomers of disopyramide in dogs.

The antiarrhythmic agent disopyramide comprises two enantiomers. In the present study, we examined the effects of the individual enantiomers on in vivo electrophysiology in anesthetized, closed-chest dogs. Six dogs received d-disopyramide, seven received l-disopyramide, and three dogs served as controls. Electrophysiologic measurements were performed at a series of geometrically increasing steady-state plasma concentrations of d- or l-disopyramide. Concentration-response curves were constructed for each electrophysiologic parameter, and the slopes of the regression lines of response versus plasma concentration were compared between enantiomers. Electrophysiologic parameters in the control dogs did not significantly change with time. However, stereoselective electrophysiologic effects were observed, with l-disopyramide being more potent than d-dispopyramide in prolonging sinus cycle length, Wenckebach cycle length, and atrioventricular nodal refractoriness (p less than 0.05). These findings are consistent with the established increased anticholinergic activity of the d-enantiomer which appeared to offset its local anesthetic or sodium channel inhibiting properties. Interrelationships between the autonomic nervous system and the cardiac electrophysiologic effects of disopyramide may be important in its antiarrhythmic effects.

Anesthesia↗
PubMedDate not supplied

Automated family classification in ambulatory arrhythmia monitoring.

A system to analyze ambulatory arrhythmia monitoring has been developed which is highly specific and sensitive. It has been used to process seven tapes per day (comprising clinical caseload and data for antiarrhythmic drug studies) in a clinical environment. This system has also been used to investigate two-channel ambulatory electrocardiograms, where the additional information provided is expected to improve the ability to deal with artifact and the problem of isoelectric premature ventricular contractions. A correlation of QRS complexes with operator-selected decisions has also been tested. While time-consuming, it is reliable and amenable to optimization solutions.

Ambulatory Care↗
PubMedDate not supplied

Perspectives on cardiovascular monitoring in 1977.

During the past several decades, cardiovascular monitoring has been used with increasing frequency. Measurement of pressures, flows, cardiac rhythm, and blood gases permits the physician and surgeon to apply physiological concepts for treating patients with disease. More complex surgical procedures are now possible. Higher postoperative survival rates have resulted directly from careful monitoring and treatment in the postoperative care units. Operations may be performed with greater safety because of cardiovascular monitoring in the operating room. The relationship between the respiratory system and the circulatory system in managing patients with disease and in patients who are postoperative has been elucidated by new monitoring techniques. The value of extending monitoring to ambulatory patients is just being appreciated, and techniques to do so have been developed. The future offers much promise for an improved quality of medical care, with advanced techniques in cardiovascular monitoring that will be developed for use in the very near future. It is our hope that this symposium will provide useful information for those responsible for selecting such systems in future years.

Arrhythmias, Cardiac↗