Biomedical subjects

D G Pace

Publications and source records attributed to D G Pace.

4 recordsLinked to original sources

PubMed1979

Digoxin-induced decrease in intraocular pressure in the cat.

A constant intravenous infusion of digoxin (2 micrograms/kg/min) to alpha-chloralose-anesthetized cats produced a progressive decrease in intraocular pressure with increasing doses of digoxin between 60 micrograms/kg and drug-induced ventricular arrhythmia which occurred at a mean dose of 172 micrograms/kg. Digoxin elicited a 40% decrease in intraocular pressure just prior to ventricular arrhythmia compared to a decrease of only 10% with a control infusion of diluent in the same animal (P less than 0.05). There was no significant difference (P less than 0.1) between changes in blood pressure and heart rate observed in the experimental versus the control infusions. The decrease in intraocular pressure may result from inhibition of the Na-K-ATPase in the ciliary body.

Animals↗

PubMed1978

Interactions between digoxin and brief vagal bursts influencing atrioventricular conduction.

The interaction between intravenous injections of digoxin (20 microgram/kg every 15 minutes) and brief electrical bursts of vagal stimulation was determined in chloralose-anesthetized dogs. Vagal effect curves were generated to characterize the effect of brief vagal stimulus bursts on atrioventricular conduction. These curves were fit with an analytic expression from which the following parameters were derived as the experimental observations: 1) the maximal change in atrioventricular conduction (deltaPRmax), 2) the time after the stimulus at which atrioventricular conduction was maximally inhibited (Tmax) and 3) the width of the vagal effect curve at one-half the maximal amplitude (TD). Digoxin administration significantly (P less than .05) increased deltaPRmax, Tmax and TD by 21.6 +/- 4.3, 50.0 +/- 16.1 and 125.5 +/- 42.4 msec, respectively, before the disruption of sinus rhythm. Diluent or saline administration did not alter deltaPRmax, Tmax or TD. In addition, digoxin produced dose-dependent increases in deltaPRmax. These results suggest that digoxin vagal interactions not only affect the PR interval but also the time to the maximum delay in atrioventricular conduction and the length of time for depressed conduction after brief bursts of vagal activity.

Animals↗

PubMed1976

Role of the nervous system in experimentally induced arrhythmias.

The purpose of our studies was to examine the role of the nervous system in arrhythmias produced by digitalis overdose and coronary artery occlusion in the cat. This was done by observing the effect of these arrhythmogenic procedures on cardiac efferent neural activity and then determining whether any observed alteration in neural activity contributed to the cardiac rhythm disturbances evoked by digitalis and coronary artery occlusion. Our data indicate that both procedures used to evoke arrhythmias activate each division of the autonomic nervous system. Activation of the sympathetic nervous system resulted in a deleterious effect on cardiac rhythm whereas activation of the parasympathetic nervous system, in general, resulted in a beneficial effect on cardiac rhythm. With coronary occlusion, the role exerted by the nervous system depended on the anatomic location of the involved myocardium. Studies directed at elucidating the mechanisms whereby the nervous system caused cardiac rhythm disturbances indicated that there may be an important difference between the antiarrhythmic efficacy of beta-adrenergic blockade and bilateral stellate ganglionectomy. The latter procedure proved to be a more effective way of removing deleterious sympathetic neural effects on the heart. In conclusion, our findings suggest that the development of new drugs for treating arrhythmias resulting from digitalis and coronary occlusion should be aimed at finding drugs that act to either depress central sympathetic outflow or enhance parasympathetic effects on the ventricle.

Animals↗

PubMed1976

Neuroexcitatory effects of digoxin in the cat.

The effect of intravenous injections of digoxin (20 mug/kg every 15 minutes) on spontaneously occurring activity in autonomic efferent nerves, motor nerves, afferent nerves, electrocardiogram and on arterial blood pressure was evaluated in chloralose-anesthetized cats. Administration of digoxin enhanced neural activity in pre- and postganglionic cardiac synpathetic nerves and this enhancement occurred near the time the disturbances in ventricular rhym were noted. Neural activity continued to increase during ventricular tachycardia and maximum enhancement was observed just proir to ventricular fibrillation. Similar results were observed when digoxin was administered to animals in which neural activity was recorded from preganglionic splanchnic and superior cervical nerves. Digoxin administration also increased discharge frequency from vagus (efferent fibers), phrenic and carotid sinus nerves. Denervation of cardiovascular reflexogenic areas prevented the increased discharge in vagus nerves, reduced it in phrenic nerves, but did not affect nerve discharge in sympathetic nerves. These results suggest that digoxin-induced hyperactivity in synpathetic nerves was related to a central nervous system effect of the drug, whereas the mechanism for the digoxin-induced hyperactivity in vagus nerves involved a peripheral reflex effect of the drug. Both sites were involved in the digoxin-induced hyperactivity in phrenic nerves. Enhancement of cardiac sympathetic nerve activity appeared to be responsible for the ventricular arrhythmias provoked by digoxin as 1) a temporal relationship was observed between augmented nerve activity and arrhythmia development, 2) a centrally acting sympathetic nervous system depressant drug, clonidine, converted the ventricular arrhythmia to normal rhythm, and 3) removal of sympathetic influence to the heart by spinal cord transection decreased the sensitivity of the heart to the arrhythmogenic effect of digoxin. These results suggest that digoxin partially responsible for its cardiotoxic effects.

Adrenal Glands↗