Rafael Mendez

The Action of Several Cardiac Glycosides on Conduction Velocity and Ventricular Excitability in the Dog Heart

The effects of digitoxin, ouabain, lanatoside C and K-strophanthoside on ventricular excitability and conducion velocity were studied. All agents caused an initial slight increase followed by a decrease of ventricular excitability, and depression of A-V and intraventricular conduction. Conduction, while depressed in the specialized tissue, was well maintained in the muscle itself until death of the heart. No significant qualitative differences between the glycosides were observed.

The search for a digitalis substitute II milrinone (Win 47203) its action on the heart-lung preparation of the dog

Milrinone (Win 47203) is a dipyridine related to amrinone, which is about 20-50 times as effective as amrinone when assayed on cardiac contractility. In dog heart-lung preparations, milrinone in a concentration of 0.25-0.5 microM produced a near maximal positive inotropic effect on a variety of acute heart failures. This dosage produced a minimal increase in heart rate and reduced the PR interval. Large doses of milrinone did not produce cardiac irregularities and in Nifedipine heart failure with ventricular irregularities, it eliminated these irregularities. Papaverine-induced heart failure was resistant to ouabain, epinephrine and milrinone therapy. In the presence of positive inotropic amounts of papaverine or theophylline, a pentobarbital heart failure was superimposed. This heart failure responded poorly to milrinone, although it responded to both the addition of epinephrine and ouabain. It is thus possible that milrinone, papaverine and theophylline have closely related sites of action.

Singular effects of a new short acting cardiac glycoside in Purkinje cells

Abstract A new cardiac glycoside, which possessed all the actions of digitalis, differed in its effects on isolated Purkinje fibers in the 2 following respects: (1) the effects developed very quickly and were quickly reversible even after automaticity and excitability were lost; (2) a given effect could be maintained at a stable level for relatively long periods.

Cardiac effects of six actodigin (AY-22,241) - related semisynthetic glycosides

Six actodigin (AY-22,241)-related semisynthetic glycosides (with the C-3 natural linkage of the lactone ring to the steroid nucleus, transposed to C-2) were assayed in failing hearts of canine heart-lung preparations. Two compounds, with additional small modifications in the steroid nucleus, were incapable of reversing heart failure. Two others, an isodigoxigenin and an isogitoxigenin derivative, were only slightly active. However, the two other actodigin-derived compounds, with methyl groups at the lactone C-4, were very active. Compound 5 had the methyl group in beta position and was 2.5 times more potent than actodigin. Compound 6, with the methyl group in alpha position, had a potency similar to that of actodigin. In the anesthetized and vagotomized dog, their toxic effects (to the point of atrioventricular dissociation) were short lasting and completely reversible. Both of these agents had a wide margin of safety (relationship between the minimal therapeutic, irregularity and lethal doses).

Antiarrhythmic actions of clemizole as pharmacologic evidence for a circus movement mechanism in atrial flutter

SummaryThe antihistaminic clemizole was studied as an antiarrhythmic in a preparation in which two arrhythmias of different nature and mechanism were produced in the right atrium of anesthetized dogs. One of the arrhythmias was a circus movement flutter induced by the method of Rosenblueth and García Ramos; the other, an ectopic focus induced by local application of aconitine in the auricular appendage, electrically isolated from the rest of the atrium. Clemizole selectively converted the flutter to sinus rhythm with little action on the coexistent aconitine dysrhythmia. It did not modify arterial pressure. In effective doses the wave length of the impulse was increased by prolongation of the refractory period without significant reduction in conduction velocity. Similarly, in subendocardial cells of isolated rat atria, clemizole in appropriate concentrations retards repolarization with little effect on the rate of depolarization. These results afford pharmacological evidence for the existence of atrial circus movement arrhythmias which can respond to prolongation of the refractory period unaccompanied by effects on other properties of the tissue. Other arrhythmias, self-sustained by the discharge of an ectopic focus, such as the tachysystole produced by aconitine, are not suppressed by similar increase in the refractory period.

A Study of the Digitalis-like Action of Thevetoidin in Man

The effect of thevetoidin in heart failure has been studied. Thevetoidin has a prompt and partly transient digitails-like effect which is shown on the heart rate, the circulatory velocity and on the P-R and Q-T intervals of the electrocardiogram, and also a cumulative effect similar to that of strophanthin. Due to its intense vagal effect and its quick digitails-like action, paroxysmal auricular tachycardia was stopped in two patients out of three in from three to four minutes. Its therapeutic advantages and disadvantages are discussed.

Disparity between the antihistaminic and antiarrhythmic activities of chlorpheniramine and its isomers

Abstract The antiarrhythmic activity of chlorpheniramine and its dextro and levo isomers as maleates was determined in experimental cardiac arrhythmias produced in the anesthetized dog. We investigated whether there is a correlation between their H 1 antihistaminic and their antiarrhythmic activities. The antihistaminic potency of the dextro form is 100 times greater than that of the levo isomer, and 2.5 times greater than that of the racemic form. In contrast, their antiarrhythmic potency is as follows: 1) on circus-movement atrial flutter, the activity of the levo isomer is 1.4 and 2.3 times that of the racemic and dextro compounds respectively. This order of antiarrhythmic effectiveness is proportional to the degree by which each compound prolongs the wave length of the auricular impulse. None of the compounds had any significant effect on the excitability of the atrium. 2) In experimental digitalis intoxication, the levo form is 2.5 times more active than the racemic, while the dextro isomer has no effect. 3) In the ectopic focus induced in the right auricular appendix by local application of aconitine, the racemic form is 1.8 and 2.2 times more active than the dextro and levo isomers respectively. The three forms of chlorpheniramine showed weak and similar anticholinergic activity. These results indicate that, in some types of arrhythmias, the activity of chlorpheniramine and its isomers is not related to its antihistaminic potency, and that the antiarrhythmic properties of these agents may vary according to both the isomer and the type of arrhythmia being studied.

The action of perseitol heptanitrate on the coronary circulation in dogs

SummaryPerseitol heptanitrate, prepared by nitration of the 7 carbon heptanol, perseitol, extracted from the seed of the Mexican avocado, was compared with other organic nitrates in its action on the coronary circulation of dogs. When injected into the coronary circulation of isolated hearts perfused from a donor dog, or of hearts prepared in situ, its coronary dilator action was qualitatively similar to the effects of nitroglycerin, mannitol hexanitrate, and pentaerythrityl tetranitrate. Upon intravenous injection, the longer chain nitrates were from 8 to 15 times less active than nitroglycerin in their effects upon coronary flow and arterial pressure.