Studies on digitalis. 13. A comparison of the effects of potassium on the inotropic and arrhythmia-producing actions of ouabain.

Abstract

Although it is generally recognized that digitalis-induced arrhythmias can be suppressed by the administration of potassium (1-3), it is not clear whether the potassium ion also influences the positive inotropic effect exerted by the glycosides on the intact mammalian heart. Clarification of this problem is important in the understanding of the interrelationships between the actions of glycosides and potassium, and is clinically significant in view of the frequency with which potassium is administered to patients who are or have been receiving digitalis. Accordingly, the present investigation was undertaken to determine the manner in which potassium suppression of ouabaininduced arrhythmias affects the augmentation of ventricular contractile force produced by the administration of the glycoside. MethodsTen mongrel dogs, weighing between 10 and 25 kg, were anesthetized with intravenous sodium pentobarbital (35 mg per kg) and ventilated with a positive displacement pump that was supplied with a mixture of room air and 100% 02. The right ventricle was exposed through a median sternotomy, a Walton-Brodie strain gauge arch (4) was sutured to the right ventricle, and the muscle segment beneath the gauge was stretched approximately 50% beyond its initial length. This maneuver allows recording of the changes in contractile force of the segment of myocardium between the points of attachment of the gauge despite some changes in right ventricular dimensions (5). Heparin, 5 mg per kg, was administered intravenously. With a compressed air-blood reservoir that was connected to a femoral artery through a large bore cannula, mean arterial pressure was maintained constant despite any changes in blood volume that might have occurred as a consequence of bleeding or blood withdrawal for plasma K concentration. Body tempera-* Submitted for publication June 9, 1965; accepted November 26, 1965. f Address requests for reprints to Dr. Eugene Braunwald, Cardiology Branch, National Heart Institute, Bethesda, Md. 20014. ture was monitored with a thermistor probe placed in the superior vena cava and was maintained constant with heating pads. Femoral arterial pressure was measured with a Statham P23D strain gauge transducer, and arterial blood was withdrawn at intervals for determinations of plasma K by flame photometry. Right ventricular contractile force, arterial pressure, and a limb lead of the electrocardiogram were recorded continuously on a direct-writing oscillograph. In two of the ten animals the sinoatrial node was crushed and heart rate maintained constant by stimulating the right atrium at a rate just above the spontaneous rate. Two animals had undergone bilateral adrenalectomy 1 week before the experiment and were then maintained on steroid replacement therapy.After control measurements, an intravenous dose of ouabain, 30 tzg per kg, was administered over a 5-minute period. Ten to 15 minutes later a constant infusion of ouabain, 30 jzg per kg per hour, was begun and was continued for the remainder of the experiment. Ouabai...

Effects of 4 Classes of Cardiovascular Drugs on Ventricular Function in Dogs with Mitral Regurgitation

“…The single dose of each drug used was obtained from the literature as a common or usual dose. 15,[17][18][19] An additional study might be to select doses escalating from no effect to one in which signs of toxicity are manifested.…”

The effects of diphenylhydantoin and potassium on the biological activity of ouabain in the guinea‐pig heart

“…The results of this study would suggest that the effect of DPH and K on the positive inotropic response of ouabain should be examined under conditions in which only positive inotropy and not arrhythmia is present. Apparent increases in ouabain inotropy due to DPH and K measured near the time of ouabain toxicity (see Scherlag et al, 1968;Williams et a!., 1966) may be misleading if the enhancement in inotropy seen in the presence of the antiarrhythmic agents is thought to occur at all time periods of drug interaction.…”

The influence of reduced serum potassium level on the toxicity of some cardenolides in guinea pigs

“…A similar change in toxicity by variation of the extracellular potassium concentration has already been reported in the intact animal (Marcus et al, 1969 andHall et al, 1977;Steiness, 1978) On the contrary, reports on the influence of extracellular potassiumvariations on the ouabain-induced toxicity are rather divergent and support in part the (unexpected) missing effect of the altered serum-potassium concentration in the present study. Whereas some findings in the dog as well as in the rabbit indicate the well-known potassium-digitalis antagonism for ouabain (Baker, 1947;Williams et al, 1966; Lown and Wittenberg, 1968), contradictory results have been reported in the guinea pig by Greeff and Knippers (1964) and Schaumann and Chatoor (1966). Thus these differences of the potassium variation on the ouabain-induced toxicity may result from the different species used.…”