Potassium channels in the cardiovascular system.

In vitro and in vivo studies suggest that opening of ATP-sensitive potassium channels following ischaemia enhances recovery of myocardial contraction, dilates blood vessels and has an antiarrhythmic effect. Different sulphonylurea compounds that block the ATP-sensitive potassium channels exert different effects on cardiac functions. Glibenclamide decrease, arrhythmogenesis during acute myocardial infarction in rats and reduces strophanthin cardiotoxicity in rabbits. Other sulphonylurea compounds, but not glibenclamide, increase arterial blood pressure and myocardial contractility. These effects may be partly secondary to blockade of ATP-sensitive potassium channels and partly due to independent cardiac and extracardiac actions. Glimepiride may have a more advantageous cardiovascular effect than glibenclamide. The studies suggest the hypothesis that deleterious cardiovascular effects of some hypoglycaemic sulphonylurea drugs may contribute to the high cardiovascular mortality rate in diabetes mellitus. An observational study suggested glibenclamide decreased the incidence of fatal myocardial infarction and development of ventricular fibrillation in patients suffering from acute myocardial infarction. Glibenclamide may also decrease the incidence of ventricular ectopic beats in digitalized patients compared with other sulphonylurea compounds. The studies suggested the survival of subjects treated with glibenclamide, insulin, or diet alone after the first attack of angina pectoris or after first acute myocardial infarction may be longer compared with those on other sulphonylurea therapies. Further large scale prospective, randomised studies are needed to determine whether the reported effects can be verified and are sufficiently large to affect clinical prescribing.

Adaptogenic and cardioprotective action of Galleria mellonella extract in rats and frogs.

Pharmacological and metabolic effects of Galleria mellonella larvae extract used in Russian folk medicine to treat cardiovascular and senile diseases were studied. It was shown that the extract possesses adaptogenic, cardiotropic, cardioprotective, and hypocoagulant properties. The extract possesses low toxicity and does not cause significant changes in biochemical parameters in the blood serum of laboratory animals. Increase in catecholamine content in the heart and aortic tissues and their decrease in adrenal glands are unfavourable effects of high doses of the extract.

[Changes in the myocardium damaged by strophanthin]. / Izmeneniia miokarda, povrezhdennogo strofantinom.

The mechanism of intoxication, produced with strophanthin (10 mg/kg) has been studied in myocardium of white rats. Area, perimeter and factor of form in mitochondria, ratio of the mitochondrial surface area with injured external membranes to the whole mitochondrial area, agranular sarcoplasmic network and T-system area, changes in myofilaments, Z-lines, length of sarcomeres have been estimated. Changes in succinate dehydrogenase, lactate dehydrogenase and in reduced forms of nicotinamide coenzymes activity has been investigated histochemically. Adenosine triphosphate (ATP) prevents appearance of ultrastructural and histochemical disturbances, produced with strophanthin. However, the protective effect of ATP is not sufficient. Adenosine monophosphate, penetrating across the cell membrane, is supposed to produce a greater curative effect.

[Relation between extra- and intracardiac anti-strophanthin properties of anti-arrhythmic agents]. / Sootnoshenie ékstra- i intrakardial'nykh antistrofantinovykh svoistv antiaritmicheskikh veshchestv.

Animal experiments have shown that beta-adrenoblockers have the most marked antistrophanthin properties while antiarrhythmic agents with locally anesthetic attributes are less active. All the substances studied have proved to be ineffective on the cellular model of strophanthin arrhythmia. The data obtained suggest that the antiarrhythmic effect of the substances under study including beta-adrenoblockers is exercised on the level of the receptor apparatus of the postsynaptic membrane. The membrane stabilizing properties do not play the decisive role in ensuring the antiarrhythmic effect in strophanthin arrhythmia.

[Cardiotoxicity of strophanthin for rats and its correction with anaprilin in coronary-related and non-coronary-related damage to the myocardium and acute cardiac insufficiency]. / Kardiotoksichnost' strofantina dlia krys i ee korrektsiia anaprilinom pri koronarogennom i nekoronarogennom porazhenii miokarda i ostroi serdechnoi nedostatochnosti.

It has been shown in rat experiments that non-coronarogenic injury to the myocardium induced by isadrin reduces the tolerance to the cardiotoxic action of strophanthine more powerfully than coronary artery occlusion. The physical overloading until complete exhaustion induced by swimming raises the cardiotoxicity of strophanthine to the same degree as non-coronarogenic injury to the myocardium. Hypersensitivity to strophanthine is successfully corrected by the beta-adrenoblocker anaprilin.

Effect of cardiac glycosides on the coronaries: physiologic and morphologic studies in the dog heart.

The effect of K- strophanthoside on coronary blood flow (CBF) was studied in open chest dogs anaesthetized with pentobarbital sodium. K- strophanthoside (3.5 and 7.0 X 10(-8) mol X kg-1 i.v.) elicited a dose-dependent decrease of CBF and an increase of late diastolic coronary resistance. Intracoronary injections of the drug (1.2 X 10(-8) mol) produced selective coronary constriction. The haemodynamic pattern indicated a direct vasoconstrictor effect, independent of the extracoronary (cardiotonic) action of the drug. In the polarization microscope Romh anyi 's aldehyde bisulphite-toluidine blue (ABT) reaction as adapted for the detection of cardiac glycosides showed profuse binding of strophanthoside to the coronary vessel wall. K- strophanthoside significantly reduced the CBF increase elicited by adenosine infusion (2 X 10(-7) mol X kg-1) into the left heart. Verapamil (4 X 10(-7) mol X kg-1, i.v.), on the other hand, counteracted the strophanthoside action on CBF. The results suggest that restricted intracellular availability of Ca2+, a prerequisite of physiologic CBF increase, is opposed by cardiac glycosides.

Effects of calcium antagonists on coronary spasm and pulmonary artery contraction in comparison to their antagonistic action against K-strophanthin in isolated guinea pig atria.

The contraction of the potassium depolarized pulmonary artery of the guinea pig was diminished by the calcium antagonists nifedipine, gallopamil, diltiazem, verapamil and prenylamine. The drugs are listed here in order of activity. The uptake of 45Ca of the depolarized pulmonary artery was reduced by nifedipine, verapamil and prenylamine in this order of activity. The depression of the coronary flow of the isolated guinea pig heart, which was brought about by barium chloride, antigenic rabbit serum or vasopressin plus oxytocin was reduced by infusion of prenylamine. The positive inotropic effect of K-strophanthin on the isolated, electrically stimulated left atrium of the guinea pig heart was reduced by gallopamil, verapamil, prenylamine, diltiazem and nifedipine in this order of activity.

[Correction of hypersensitivity to strophanthin in experimental myocardial infarction by pharmacologic effects on extracardiac innervation]. / Korrektsiia giperchuvstvitel'nosti k strofantinu pri éksperimental'nom infarkte miokarda farmakologicheskimi vozdeistviiami na ékstrakardial'nuiu innervatsiiu.

Experiments on 176 cats with experimental myocardial infarction were made to study alterations in ouabain tolerance under pharmacological effects on extracardial innervation. It was shown that elimination of sympathetic innervation at different levels by benzohexonium, ornid and anapriline, as well as its relative weakening by proserine favoured the correction of hypersensitivity to ouabain in acute myocardial ischemia. Potentiation of sympatic effects by ephedrine and abolition of parasympathetic innervation by atropine increased ouabain cardiotoxicity.

[Effect of lithium preparations on cardiac arrhythmias induced by strophanthin]. / Vliianie preparatov litiia na serdechnye aritmii, vyzvannye strofantinom.

It was shown in experiments on cats that when strophanthin K injected intravenously induced ventricular arrhythmias followed by an insignificant reduction of the sympathetic activity (recorded from the cardiac nerve), lithium chloride and lithium hydroxybutyrate did not produce any effect on arrhythmia but lowered the sympathetic activity. When strophanthin-induced arrhythmias were accompanied by an increase in the sympathetic activity (animals with vagus section and denervation of the sinocarotid and cardioaortal zones), lithium hydroxybutyrate led to the diminution of the sympathetic activity and exerted antiarrhythmic effects. It is concluded that in the mechanisms of the antiarrhythmic effect an important role belongs to its depressant effect on the hyperactivated adrenergic extracardiac apparatus.

[Effect of strophanthin and cytochrome C on myocardial contraction and the incidence of shock and ventricular fibrillation in experimental myocardial infarct]. / Vliianie strofantina i tsitokhroma C na sokratitel'nuiu funktsiiu miokarda, chastotu shoka i fibrilliatsii zheludochkov pri eksperimental'nom infarkte miokarda.

High ligation of the interventricular artery caused ventricular fibrillation in the first 2--4 minutes in 20% of cats. In the remaining animals myocardial contractility diminished to half its initial value. After that, contractility increased gradually. In cardiosclerosis myocardial contractility reduced by 20--30%. Ligation of the interventricular artery on the background of cardiosclerosis induced cardiogenic shock in half of the animals. Cytochrome C does not reduce the diminution of myocardial contractility after ligation and has a marked antifibrillatory effect. Strophantin does not affect the diminution of contractility of a healthy myocardium but reduces the decrease in contractility of a sclerosed myocardium and also promotes the development of ventricular fibrillation following ligation of the interventricular artery.

[Inhibitory effect of the calcium antagonist fendiline on digitalis glykosides induced contractions in the guinea pig terminal ileum (author's transl)]. / Die Hemmwirkung des Ca++-Antagonisten Fendilin auf die durch Herz-Glykoside erzeugten Kontraktionen am terminalen Ileum des Meerschweinchens.

The 10 mm muscle-strips from the guinea pig terminal ileum digitalis glycosides (0.4 microgram/ml beta-acetyl-digoxin or 0.5 microgram/ml k-strophanthin) induce contractions which are dose-dependently and reversibly prevented by the calcium antagonist N-(2-benzyl-ethyl)-N-(1-phenyl-ethyl)-amine hydrochloride (fendiline, Sensit) (0.01--1 microgram/ml). Therapeutic use of calcium antagonists for manifest symptoms of digitalis intoxication (diarrhoea, intestinal infarctions) is discussed as these symptoms may be caused by digitalis-induced increase of intracellular calcium ions.

[Strophanthin sensitivity in disorders of cardiac blood supply, altered immunologic reactivity and under the influence of several pharmacologic agents]. / Chuvstvitel'nost' k strofantinu pri narushennom krovosnabzhenii miokarda, izmenennoi immunologicheskoi reaktivnosti i pod vliianiem nekotorykh farmakologicheskikh sredstv

Tests conducted with 125 cats demonstrated that occlusion of the coronary artery causes a higher sensitivity to the bathmotropic action of strophanthin, but does not have any effect on the magnitude of its lethal dose. The efficaciousness of potassium orotate and also of Na2EDTA in combinations with anapriline and isadrine, as regulators of the sensitivity to the toxic effect of strophanthin, was investigated. Immunization of cats with a homocardiac antigen was found to produce biphasic changes in the sensitivity to the toxic effect of strophanthin associated with the duration of antigenic stimulation.

[Antiarrhythmic activity of trimecaine in experimental arrhythmia and its effect on the heart conduction system]. / Protivoaritmicheskaia aktivnost' trimekaina pri eksperimental'nykh aritmiiakh i ego vliiani na provodiashchuiu sistemu serdtsa.

The anesthetic trimecaine is shown to be capable of eliminating the flutter of atria in dogs simulated by an electric stimulation of the myocardium and atrial fibrillation in cats induced with aconitin and precludes ventrical fibrillation in rats arising due to intoxication with calcium chloride. Trimecaine noticeably mitigates the toxic effect of strophanthin. While depressing the automatism of the sinoatrial node the drug does not affect the conduction function.

The entity of non occlusive mesenteric ischemia: strophanthin effect on mesenteric blood flow in experimental animals.

Digitalis glycosides have the well known positive inotropic effect on the heart. Their effect on extracardiac vascular smooth muscle receives increasing attention. In experimental animals a significant decrease in mesenteric blood flow and an increase in mesenteric vascular resistance could be shown. Angiography of main mesenteric arteries, smaller arteries, and arterioles reveal typical vasoconstriction. Angiomorphometric measurements show good correlation between the decrease in vascular diameter and the increase in vascular resistance.