On the cardioprotective effect of adenosine.

In isovolumically perfused Langendorff heart preparations of guinea pigs adenosine-depending on the experimental protocol-more or less could prevent the hypoxia-induced decrease in myocardial adenosine triphosphate [ATP], creatine phosphate [CP], glycogen and increase in lactate, i.e. showed cardioprotection.

Long-lasting treatment with adenosine receptor antagonists: effects on hypoxic tolerance and vascular responsiveness.

In electrically driven myocardial preparations obtained from chronically methylxanthine-[aminophylline (APH) and 8-phenyltheophylline (8-PT)] or solvent(DMSO)-treated guinea pigs no differences were found in alteration of mechanical activity under hypoxia and reoxygenation. The vasoconstrictor effects observed after in vitro exposure of pulmonary arterial preparations (excised from either methylxanthine- or solvent-treated guinea pigs) to both noradrenaline and PGF2 alpha were also similar. In methylxanthine-treated vascular tissues, however, nitroglycerin and NO exerted more pronounced vasorelaxant effect than in specimens prepared from solvent-treated guinea pigs.

[Effect of Chinoin-103 on K(+)-activated pNPPase in the rat heart].

Effect of a new beta receptor blocking agent, an aryl oxybutanolamine derivative, the Chinoin--103 on K(+)-activated pNPP-ase activity has been studied. Propranolol and practolol were used as reference substances. It has been established that Chinoin-103 in concentration of 10(-4) M significantly hindered total pNPP-ase activity.

Changes in sarcolemmal adenosine triphosphatase activity and in ouabain sensitivity of rat myocardium in isoproterenol-induced cardiac hypertrophy.

Sodium, potassium-activated adenosine triphosphatase (ATPase) activity and the sensitivity of rat myocardium to ouabain was studied in isoproterenol (IPR)-induced cardiac hypertrophy. IPR in a dose of 5 mg/kg was administered to rats intraperitoneally, once daily, for seven days. Left ventricular trabeculae originating from IPR-treated rats were significantly less sensitive than controls to ouabain-induced positive inotropy.

Adenosine decreases the fibrillation threshold in atrial myocardium.

The action of adenosine on the fibrillation threshold, effective refractory period, electric diastolic threshold and mechanical activity of the atrial and ventricular myocardium was studied in vivo and in vitro. In anaesthetized, open-chest cats, the atrial fibrillation threshold significantly decreased under adenosine-infusion (1 mumols/kg/min). In electrically stimulated atrial myocardium of cats, adenosine (10 mumols/l-1 mmol/l) was capable of evoking a concentration-dependent decrease in electric diastolic threshold and shortening the functional refractory period.

[Effect of propranolol on ouabain-sensitive Na+,K+-ATPase activity of the rat heat].

Effect of propranolol on activity of basal ATP-ase measured in presence of Mg2+ activator, on that of total ATP-ase determined in presence of Mg2+, Na+, K+ activators and on that of Na+,K+-activated ATP-ase calculated from the difference of the previous two ones has been studied. Propranolol has not considerably influenced basal ATP-ase activity in 10(-7)-10(-4) M concentrations, 30-50% inhibition has been found in 1 X 10(-3)-5 X 10(-3) M concentrations. Effect of propranolol on total ATP-ase activity has been found to be dependent on doses and inhibition has been greater than inhibition experienced in case of basal ATP-ase.

[Effect of Chinoin-103 on Na+, K+-activated adenosine triphosphatase of the rat heart].

Effect of a new beta-blocking agent, a cardioselective aryl oxybutanolamine derivative, the Chinoin-103 on basal and total ATP-aze activities has been studied in total homogenizatum of rat heart. The effect has been compared to previous results of propranolol and to effect of practolol, respectively. It has been established that DL-Chinoin-103-similarly to DL-propranolol but in a little higher concentration--has significantly impeted both basal and total ATP-aze activities.

Almitrine bismesylate modulates the susceptibility of guinea pig pulmonary artery to catecholamines, PGF2 alpha and adenosine.

The action of almitrine bismesylate, a potent ventilatory stimulant drug, was studied on the contractile responses to some putative transmitters of carotid body (dopamine, noradrenaline, PGF2 alpha, adenosine) in segments of guinea pig pulmonary arteries. Almitrine (10 mumol/l) was capable of mitigating the contractions evoked by dopamine (0.3 mmol/l), noradrenaline (1 mumol/l) and PGF2 alpha (10 mumol/l) as well.

Mechanism of the antifibrillatory action of Chinoin-103, a new antiarrhythmic drug.

The studies deal with the relationship between antifibrillatory and electrophysiological effects of Chinoin-103 (CH-103) on right ventricular myocardium of cats. In experiments carried out on right ventricles of open-chested cats, CH-103 markedly increased the fibrillation threshold in a dose-dependent manner. In electrophysiological experiments performed on isolated, electrically driven right ventricular papillary muscles of cats, the drug, at the concentrations needed to increase the fibrillation threshold, decreased the maximum rate of rise of action potential (Vmax) without changing the resting membrane potential.

Study of the factors influencing cardiac growth. III. Digitoxin treatment and thyroxine-induced cardiac hypertrophy in the rat.

Thyroxine (T4) administered to rats in a dose of 1 mg/kg for 12 days induces cardiac hypertrophy. The purpose of the present study was to determine the effect of prophylactic + simultaneous digitoxin treatments on the development of T4-induced cardiac hypertrophy. Digitoxin (1 mg/kg body weight) was given per os, once daily for 6 days prior to T4 administration and continued simultaneously with T4 treatment.

Alterations of contractility and sarcoplasmic reticulum function of rat heart in experimental hypo- and hyperthyroidism.

Myocardial contractility and Ca2+-pump function of sarcoplasmic reticulum (SR) were studied on hearts of untreated, thyroidectomized and thyroxine-treated rats. In hypothyroid rats the contractile force, the maximum velocity of tension development and relaxation significantly decreased (by 73.2%, 68.

Study of the factors influencing cardiac growth. II. Digitoxin treatment and isoproterenol-induced cardiac hypertrophy in the rat.

Isoproterenol (IPR) administered to rats in a dose of 5 mg/kg for 4 days induces cardiac hypertrophy. The purpose of the present study was to determine the effect of prophylactic + simultaneous digitoxin treatment on the development of IPR-induced cardiac hypertrophy. Digitoxin (1 mg/kg body weight) was given per os, once daily for 6 days prior to IPR administration and continued simultaneously with IPR treatment.

Effects of hypoxia on the guinea-pig myocardium following inhibition of adenosine deaminase by coformycin.

The effect of moderate and severe hypoxia on the electrical and mechanical activity of isolated left atria of guinea-pigs was compared in the presence and absence of coformycin, a highly specific and tight-binding inhibitor of adenosine deaminase. The myocardial actions of hypoxia (reduction in the duration of intracellularly recorded action potentials and decrease in isometric tension, maximum velocity of contraction and relaxation as well as in time to peak tension) were significantly enhanced by coformycin, when applied in a concentration of 7 mumol/l producing nearly complete inhibition of adenosine deaminase in atrial muscle. These effects of coformycin were moderate during early hypoxia (0-5 min) and became pronounced during the late phase of oxygen deprivation (5-16 min).

Antagonism between adenosine and bromobenzoyl-methyladamantylamine, a K+-channel blocker, in atrial myocardium of guinea pig.

The effect of bromobenzoyl-methyladamantylamine (BMA) on the adenosine-induced changes in the electrical and mechanical activity of the atrial muscle, and the effect of adenosine on the slow action potentials induced by BMA in K+-depolarized atrial myocardium of guinea pig were studied. BMA was able to antagonize the adenosine-induced shortening of the action potential duration and negative inotropic effect. This action of BMA was potentiated by theophylline, and reduced by dipyridamole.

Effect of induced hypothyroid state on the mechanical and electrical properties of the rat ventricular myocardium.

The effect of hypothyroid state on the transmembrane potential was studied in isolated cardiac ventricular trabeculae of rats. Hypothyroid state was induced by methimazole treatment or thyroidectomy and checked by determining serum thyroxine level. Hypothyroidism decreased the maximum rate of depolarization (Vmax) and the resting potential, increased the overshoot and the duration of action potential at 20, 50 and 90% repolarization.

Ventricular automaticity induced by bromobenzoyl-methyladamantylamine (BMA) in different membrane potential ranges in guinea pig heart.

The electrophysiological effects of bromobenzoyl - methyladamantylamine ( BMA ) were investigated in isolated electrically driven right ventricular papillary muscles of guinea pigs using conventional glass-microelectrode technique. BMA markedly increased the action potential duration, depolarized the membrane, reduced the maximum rate of depolarization (Vmax) and induced pacemaker-like action potentials. In ventricular myocardium depolarized partially (up to --40 mV) by incubation with 26 mM K+-Krebs solution, BMA induced slow action potentials.

Study of the factors influencing cardiac growth. I. Comparison of cardiomegaly induced by isoproterenol in euthyroid and thyroidectomized rats.

The purpose of the present work was to study the cardiac growth-stimulating effect of IPR in hypothyroid animals, in which the in vitro sensitivity of the myocardium to beta-adrenergic agonists is significantly decreased. To determine the degree of myocardial enlargement, wet and dry ventricle weight and myocardial RNA, DNA and protein were measured. IPR administered to euthyroid rats in a dosage of 5 mg/kg/day for 4 days induced cardiomegaly.

Comparative studies on the positive inotropic effect of isoproterenol and bromobenzoyl-methyladamantylamine in guinea pig ventricular myocardium.

The effects of bromobenzoyl-methyladamantylamine (BMA) on the transmembrane potentials, contractile force, and 42K efflux were investigated and compared to that of isoproterenol (IPR) in guinea pig ventricular myocardium. Both drugs exerted positive inotropic effect. BMA lengthened the action potential duration, depolarized the membrane, and decreased the Vmax.