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The results of experiments on narcotized cats and rats showed that the drug zatebradin produces a specific bradycardic action by reducing the heart rate and the double product, while virtually not influencing vitally important parameters of the heart activity such as the cardiac output and the mean acceleration of the aorta blood flow. The drug reduced the rise of ST segment recorded in multiple epicardial ECG leads made in narcotized cats during a 5-min occlusion of the anterior descending branch of the left coronary artery. Zatebradin was found to increase the cardiac rhythm variability in narcotized rats and decrease the rate of ventricular fibrillations during a 7-min occlusion with the subsequent 3-min coronary artery reperfusion.

The experiments with anesthetized rats showed that drugs belonging to various subclasses of class I antiarrhytmic agents (novocainamide, IA; lidocaine, IB; ethacizine, IC) produce a pronounced antifibrillatory and antiarrhythmic action under the conditions of a 7-min occlusion followed by reperfusion of the anterior descending branch of the left coronary artery. In the arrhythmia model with beta-adrenoreceptors stimulated by isoproterenol, novocainamide (IA) and lidocaine (IB) retained their efficacy, in contrast to ethacizine (IC). This difference in the behavior of antiarrhythmic drugs may be related to their different antiarrhythmogenic potentials.

Experiments with a 7-min occlusion followed by reperfusion of the left coronary artery in narcotized rats showed that antiarrhythmic drugs of various classes--ethacizin (class I), AL-275 (class III), and CM-345 (class V)--produce pronounced antifibrillatory and antiarrhythmic effects. AL-275 and CM-345, in contrast to ethacizin, retained their efficacy under the conditions of isoproterenol-induced stimulation of beta-adrenoceptors. This difference in behavior is probably explained by dissimilar effects of the antiarrhythmics on the ion channels of cardiomyocite membranes.

The new drug Bradizol (SM-345), a 2-mercaptobenzimidazole derivative producing a specific bradycardic effect, is quite rapidly eliminated upon intravenous bolus in anaesthetiezed cats. After a combined injection (bolus followed by a 60-min infusion), a constant bradizol concentration in the blood plasma is observed over a time period of 90 min. The bradizol-induced bradycardic effect and the drug concentration in the blood plasma are tightly correlated. Upon per os administration of bradizol to the experimental animals, neither the drug is detected in the blood plasma, nor the bradycardic effect is observed. It is suggested that bradizol, possessing antiarrhythmic, antifibrillator, and antiischemic properties, can be used (by intravenous injections) for the therapy of patients with diverse tachyarrhythmia geneses, including those with the ischemic heart disease.

Experiments on narcotized cats demonstrated that the derivatives of 2-mercaptobenzimidazole possessing the properties of specific bradycardic agents and coded as CM-251, CM-266, and CM-345, reduce the mean rise of segment ST on numerous leads of the epicardial electrogram during 5-min occlusion of the anterior descending branch of the left coronary artery. The agents stabilize the heart pumping and contracting functions under conditions of 30- and 60-min reperfusion of the coronary artery, respectively. It is concluded on the grounds of the obtained data that the 2-mercaptobenzimidazole derivatives possess a marked anti-ischemic action.

It was shown in experiments on aconitine, calcium chloride, and epinephrine models of heart rhythm disorders that derivatives of 2-mercaptobenzimidasole possessing the properties of specific bradycardiac agents coded as SM-251, SM-266, and SM-345 cause a marked antiarrhythmic effect. SM-266 and SM-345 reduce considerably the number of ventricular fibrillations and the life-hazardous arrhythmia occurring during 7-min occlusion and subsequent reperfusion of the coronary artery in anesthetized rats. The agents under study reduced the ectopic heart rate in Harris' conscious dogs. It is concluded that the studied 2-mercaptobenzimidasole derivatives exert a marked antiarrhythmic and antifibrillatory effect.

Experiments on anesthetized cats and rats showed that 2-mercaptobenzimidazole derivatives, known as SM-266 and SM-345, induced marked and long-term bradycardia, increased the stroke output, and reduced the requirements of the heart of oxygen. The drugs had practically no effect on systemic arterial pressure, cardiac output, and heart contractility. Studies on isolated frog venous sinuses disclosed that bradycardia induced by the drugs under study was related to the decrease caused by them in the velocity of slow diastolic depolarization directly in the pacemaker cells on the sinus node. On grounds of the obtained results it is concluded that the drugs under study may be related to a new group of specific bradycardiac agents.

The experiments with unconscious cats and dogs have demonstrated that the calcium antagonist nimodipine has a profound anti-ischemic property. The drug reduces the average value of ST-segment elevation in multiple epicardial ECG leads, during acute myocardial ischemia. Nimodipine maintains cardiac pump and contractile functions, elevates ATP levels in the arbitrarily intact and ischemic myocardium of the left ventricle during 40-min occlusion and 60-min reperfusion of the coronary artery. The protective action of the drug is unassociated with enhanced collateral coronary circulation.

In the experiments on anesthetized cats and dogs it was shown that calcium antagonists nimodipine and flunarisine possessing the predominant action on the cerebral vessels exert a significant effect on the blood supply and the activity of the cardiac muscle. Administration of the drugs causes bradycardia, increases the total coronary blood flow. Nimodipine enhances the contractile function of the myocardium, flunarisine fails to change it. Under ischemia of the cardiac muscle the drugs increase the blood supply of only the intact zones of the left ventricle without influencing positively the blood supply of the ischemic focus itself.

In experiments on anesthetized cats and dogs it was shown that the anti-ischemic action of verapamil and diltiazem injected intravenously in acute permanent occlusion of the coronary artery is not related to their effect on the collateral blood supply to the myocardial ischemic focus. The protective effect of the drugs in this case is due to other mechanisms one of which is a decrease of oxygen consumption by the heart.

In the experiments on different animal species (mice, cats, dogs) lithium hydroxybutyrate has been shown to have antihypoxic and anti-ischemic effects. Lithium hydroxybutyrate improved the functional state of the ischemic myocardium, stimulated the accumulation of macroergic phosphates (ATP) in the heart, protected the ischemic myocardium and delayed the progression of the reversible ischemic damage into the irreversible one. The improvement of the collateral coronary circulation plays an important role in the anti-ischemic action of the drug.