Prevention of disorders of the electric stability of the heart in experimental infarct using adaptation to hypoxia

It has been shown on rats preadapted to hypoxia in an altitude chamber that myocardial infarction induced by ligation of the coronary artery was accompanied by less disturbances in the electrical stability of the heart, namely by a twofold decrease in ventricular fibrillation threshold and a considerable decrease in the heart ectopic activity. Preliminary adaptation provided the maintenance of myocardial contractility in infarction.     

Lipid peroxidation in the myocardium in experimental infarct

Changes in the content of lipid peroxidation (LP) products and activities of antioxidant enzymes--superoxide dismutase, glutathione peroxidase and catalase in myocardium of rats after experimental infarction as well as after pretreatment with antioxidant ionol, beta-adrenoblocker inderal and verapamil, an inhibitor of slow Ca2+-channels have been studied. In the left ventricles of the control animals decreased levels of LP-products (Schiff bases and lipid hydroperoxides) have been registered as compared with right ventricles, accompanied by increased activity of antioxidant enzymes in the left ventricles. In experimental infarction the level of LP products increases and activity of antioxidant enzymes decreases both in ischemic and nonischemic regions of the heart. In nonischemic zone these changes can be prevented by pretreatment with inderal and ionol but not with verapamil.     

Disordered cardiac electrical stability in beta-adrenergic damage and antioxidant protection]

The electrical threshold of ventricular fibrillation induced by premature single impulses and the ectopic activity and also an abnormal conduction during vagus inhibition of sinus node were estimated 24 hours after the administration of isoproterenol (10 mg/kg, s/c, on time) in rats. In addition the cardiac contractile function of the left ventricle was studied. The study was performed on male Wistar rats, 250-300 body weight, under nembutal anesthesia. Isoproterenol had no effect on the contractile function in the rest and during maximal isometric load, induced by coarctation of ascending aorta. But in the treated animals the threshold of fibrillation fell more than 2-fold and the vagal bradycardia was more 2-fold then in the untreated animals. The AB-block, idioventricular rhythm and extrasystoles appeared during vagal bradycardia in treated animals, while in the untreated ones there were no any disturbances. The preliminary administration of the antioxidant ionol (BMT, 30 mg/kg, per os, in sun oil) prevented the enumerated shifts.     

Combined use of hyperbaric oxygenation and antioxidants in the therapy of experimental myocardial infarct

In rabbits with experimental myocardial infarction, the combined use of hyperbaric oxygenation and ionol greatly potentiated the effect of the antioxidant on contractile function of the left ventricle, the time course of antioxidant lipid activity and superoxide dismutase activity of the myocardium.     

DNA changes in a nonischemic area of the rat myocardium in experimental myocardial infarct and its prevention

DNA damage and repair in the nonischemic area of the heart were analyzed after experimental myocardial infarction to evaluate the effect on these processes of the beta-blocker inderal and lipid peroxidation inhibitor ionol. It was found that in the nonischemic area of the heart, DNA damage was manifested by the decreased polymerism averted to a significant degree by inderal and ionol which interfered with postinfarction activation of lipid peroxidation. Accordingly, inderal and, to a greater degree, ionol reduced postinfarction activation of DNA repair synthesis in the nonischemic area of the heart.     

Effect of stress and the antioxidant ionol on the biosynthesis of catecholamines and the content of dopamine in the heart and adrenal glands

The effects of a synthetic antioxidant ionol (dibunol) on the biosynthesis and content of catecholamines in the heart and adrenal glands were studied. It was shown that in stress a mobilization of catecholamine reserve is combined with a considerable increase in dopamine concentration. In conditions of physiological rest, ionol did not affect the studied indices of adrenal catecholamine biosynthesis, while in the heart it enhanced the dopamine synthesis and content. With ionol administration, stress did not suppress but, on the contrary, increased the neuronal uptake and noradrenaline biosynthesis, catecholamine concentration remaining practically unchanged. Simultaneously, a manyfold increase in the biosynthesis along with a considerable increase in the concentration of dopamine developed in both organs. The data obtained suggest that ionol realizes its stress-defensive effect to a great extent due to the activation of catecholamine biosynthesis and to a concomitant increase in dopamine accumulation.     

An electrophysiological study of the anti-arrhythmia effect of antioxidant ionol]

The paper describes the study of anti-arrhythmia effects of ionol. In isolated rabbit papillary muscle, ionol (a) had no effect on the depolarization-induced automaticity; (b) did not influence early afterdepolarizations: (c) delayed the onset of post-depolarizations initiated by Ca-overload and therefore inhibited the ectopic focal activity in myocardium. In isolated left auricles of rabbit, ionol suppressed the shortening of the excitation wavelength induced with adrenaline and thus protected the heart of reentry and consequent rhythm disturbances.     

The dose-dependent effect of 3,5-dicarbomethoxyphenylbiguanide on activity of the glutathione antioxidant system in heart and blood serum of rats with experimental myocardial infarction

Administration of a synthetic compound with predicted anti-ischemic and cardioprotective activity, 3,5-dicarbomethoxyphenylbiguanide (3,5-DCMPBG) to rats with experimental myocardial infarction led to a decrease in the lipid peroxidation level, glutathione peroxidase activity, the level of reduced glutathione, activity of NADP-isocitrate dehydrogenase in the heart and blood serum, and activity of glucoso-6-phosphate dehydrogenase in heart in comparison with their levels in untreated animals with myocardial infarction. This may be attributed to a decrease of free radical processes and reduction of antioxidant system loading induced by the protective effect of the administered compound. At the same time the increase glutathione reductase activity observed under these conditions in the heart and blood serum is probably associated with specific influence of 3,5-DCMPBG on this enzyme.     

Elimination of disorders of electric stability of the heart during post-infarct cardiosclerosis using adaptation to short-term stress and the antioxidant ionol

The experiments were carried out on male Wistar rats (300-400 g) subject to open chest surgery under nembutal anesthesia. One group of rats with postinfarction cardiosclerosis (PC) was exposed to short-term immobilization stress for 15 days one month after the occlusion of the descending branch of the left coronary artery. The other group of rats with PC was administered synthetic antioxidant ionol (BHT) (60 mg/kg, per os) 3 days prior to the experiments. The electrical stability of the heart was evaluated by assessing ventricular fibrillation threshold (VFT) determined by stimulation of the right ventricular apex by single premature impulses (10 ms) and by measuring the amount of ectopic beats developing during 30-sec stimulation of the right vagus (2 mA, 20 Hz). VFT in rats with PC was significantly lower, as compared to sham-operated rats (2.9 +/- 0.2 and 6.4 +/- 0.2 mA, respectively), with pronounced extrasystoles appearing during vagal bradycardia. In stress-adapted animals with PC VFT returned to the level of sham-operated rats and the amount of premature beats decreased 3-4-fold, as compared to unadapted rats with PC. Ionol (BHT) was shown to have the same effect.     

Effect of the antioxidant ionol on energy metabolic indices and heart function during acute hypoxia and subsequent reoxygenation

The effect of preliminary administration of antioxidant ionol on the heart energy metabolism and contractile function was estimated in hypoxic hypoxia and subsequent reoxygenation. The protective effect of ionol on the energy metabolism in hypoxia was shown to occur mainly at the level of glycolysis. In reoxygenation, the protective effect of ionol manifested at the level of creatine kinase system to provide a rapid restoration of the CP synthesis rate. This shift correlated with the velocity of restoration of the developed pressure and the velocities of contraction and relaxation. On the whole the data obtained correspond to the notion that creatine kinase system and ATP play an important role in the depression and subsequent restoration on the heart contractile function in acute hypoxia and reoxygenation and ionol provides more effective performance of this system and correspondingly more rapid restoration of the contractile function in reoxygenation.     

Prevention of adrenaline-induced heart damage using the antioxidant ionol

Experiments on an isolated papillary muscle of the rat heart left ventricle have demonstrated that pretreatment with the antioxidant ionol prevents the disturbances of myocardial contractility caused by administration of a large dose of adrenaline. The data obtained are in agreement with the concept that the prophylactic action of antioxidants during stress is determined by the fact that they prevent activation of lipid peroxidation in the heart under the action of excess catecholamines.     

Possible role of lipid peroxidation in the pathogenesis of arrhythmias in myocardial infarct

The effect of myocardial infarction sustained by rats on the resistance of their isolated auricles to H2O2, an inductor of lipid peroxidation (LP), was studied. Atrial resistance to the LP inductor depends on the level of developed tension (DT) and the decrease of DT leads to augmentation of atrial resistance to the arrhythmogenic effect of LP. The experimental myocardial infarction causes appreciable disturbances in the function of automatism of the auricles, 60% of which lose their capability of spontaneous contractile activity. When compared with the control under equal DT, the auricles of the "infarction" series are less resistant to H2O2: the time of arrhythmias and arrests in them are 2.3 times as much as in the control. In infarction, the pretreatment with ionol reduces both the quantity of the auricles which stopped before H2O2 administration and the quantity of the auricles responding by arrhythmia to LP induction. The data point to the possibility of the use of antioxidants for preventing arrhythmias in experimental myocardial infarction.     

Effect of abana an ayurvedic formulation,on lipid peroxidation in experimental myocardial infarction in rats

The present study was conducted to elucidate the antioxidant role of an ayurvedic formulation Abana in isoproterenol induced myocardial infarction in rats. In myocardial necrosis induced by isoproterenol, a significant increase in serum iron content with a significant decrease in plasma iron binding capacity, ceruloplasmin activity and glutathione level were observed. There was also a significant increase in lipid peroxides levels on isoproterenol administration. Activities of antioxidant enzymes like superoxide dismutase, catalase, glutathione peroxidase, glutathione-s-transferase, glutathione reductase were decreased significantly in heart with isoproterenol-induced myocardial necrosis. Abana, produced a marked reversal of these metabolic changes related to myocardial infarction induced by isoproterenol. In conclusion ayurvedic formulation Abana exerts its effect by modulating lipid peroxidation and enhancing antioxidant and detoxifying enzyme systems.     

Limited area of coronary-occlusion myocardial infarct in rats undergoing antioxidant therapy

The synthetic antioxidant dibunol, (ionol. 2,6-ditret-butyl-4-methylphenol) produces the limitation of the zone of the coronaro-occlusion myocardial infarction in rats by 15.8 and 24.2% on day 7 during daily oral administration in doses of 80 and 120 mg/kg, respectively. In the doses used, dibunol reduces the activity of glutathione peroxidase but does not change the activity of glutathione-S-transferase and superoxide dismutase in the infarction zone of the myocardium. It is concluded that free radical products play an important role in ischemic and infarction damage to the myocardium.     

Damage to the Ca2+-transport system of cardiac sarcoplasmic reticulum during emotion-pain stress

The influence of emotional-pain stress on the properties of the sarcoplasmic reticulum Ca2+-transporting system of the rat heart muscle was studied. The decrease of the Ca2+-dependent component of the Ca2+, Mg2+-ATPase activity, Ca2+-binding capacity and the rate of Ca2+-transport was found in the animals after stress. These alterations in the Ca2+-transporting system were caused by lipid peroxidation and could be prevented by the antioxidant ionol.     

Disorders of the heart contractile function in chronic hemolytic anemia and their prevention

The coronary blood flow and heart contractile function were studied on rats with phenylhydrazine-induced chronic hemolytic anemia. The coronary blood flow in the animals' hearts was increased 2.5-fold, whereas the main parameters of contractile function were reduced but insignificantly. After the coronary blood flow dropped to the control level, the pressure and contraction rate fell by 40% and the relaxation rate diminished 2-fold. Thus, the enhanced coronary blood flow in the hearts of animals with hemolytic anemia appears to be a factor that compensates for the maintenance of myocardial contractility at the subnormal level. Administration of the antioxidant ionol, an inhibitor of lipid peroxidation, coupled with phenylhydrazine did not prevent the development of anemia but made the coronary blood flow descend in the hearts of anemic animal only by 80%. Since the iron-containing products of red cell dissolution activate lipid peroxidation during hemolytic anemia, this might play a role in the occurrence of heart muscle injuries. It is suggested that ionol prevents such injuries to a considerable extent, thereby preventing the development of compensatory enhancement of the coronary blood flow and heart contractile function disturbances during its normalization.     

Preconditioning with diosgenin and treadmill exercise preserves the cardiac toxicity of isoproterenol in rats

This study was aimed to evaluate the preventive effect of diosgenin and exercise on tissue antioxidant status in isoproterenol-induced myocardial infarction (MI) in male Wistar rats. Levels of lipid peroxides, reduced glutathione (GSH), and the activities of glutathione-dependent antioxidant enzymes (glutathione peroxidise and glutathione reductase) and antiperoxidative enzymes (catalase and superoxide dismutase) in the plasma and the heart tissue of experimental groups of rats were determined. Pretreatment with diosgenin and exercise exerted an antioxidant effect against isoproterenol-induced myocardial infarction by blocking the induction of lipid peroxidation. A tendency to prevent the isoproterenol-induced alterations in the level of GSH, in the activities of glutathione-dependent antioxidant enzymes and antiperoxidative enzymes was also observed. Histopathological findings of the myocardial tissue showed a protective role for combination of diosgenin and exercise in isoproterenol (ISO)-treated rats. Thus, the present study reveals that preconditioning with diosgenin and exercise exerts cardioprotective effect against ISO-induced MI due to its free radical scavenging and antioxidant effects, which maintains the tissue defense system against myocardial damage.     

Action of natural and synthetic antioxidants on the electrical parameters and stability of natural and artificial membranes

The effect of antioxidants alpha-tocopherol and ionol on membranes of human red cells and bilayer lipid membrane (BLM) from azolektin has been studied. Ionol at concentration 4-10 mM induces the hemolysis of erythrocytes, the cells form changes are observed at concentration 2 mM alpha-tocopherol doesn't show the hemolytic properties at concentration 23 mM. The ionol concentration 1 mM doesn't change the form of the cells, but influence the passive electric parameters: the capacity (Cs) of erythrocytic membrane increases and the intracellular conductance (chi i) decreases. Tocopherol (3 mM) induces the decrease both Cs and chi i. The fast increase of membrane conductance is almost immediately registered on one side of BLM at addition of ionol (0,2-0,4 g/ml). Phosphatidylionol synthesized from ionol and contining the acyl chains C15H31 and C17H35 doesn't influence the electrical properties of BLM.     

The sensitivity of the heart to static magnetic fields

Static magnetic fields induce flow potentials in arterial flows in and around the heart, that have been detected as distortions in the ECG. The resultant currents flowing through the myocardium could alter the rate or rhythm of the heart. No such changes have been seen in animal experiments, or with humans, in static fields up to 8 T. The possible effects of such currents induced by fields larger than 8 T on cardiac pacemaker rate, and arrhythmogenesis are reviewed, using virtual cardiac tissues—computational models of cardiac electrophysiology. Arrhythmogenesis can be by the initiation of ectopic beats, or by re-entry, whose probability of occurrence is increased by any increase in the electrical heterogeneity, in particular, the action potential duration heterogeneity of the ventricle. Focal ectopic activity would be readily detectable, but since re-entrant arrhythmias are very rare events, even a large increase in their probability of occurrence still leaves them unlikely to be observed. Both of these two arrhythmogenic mechanisms would show a steep sigmoidal, or threshold dependence on induced current intensity, with the threshold for increasing the vulnerability to re-entry less than the threshold for initiating activity. Failure to observe them at fields less than 8 T provides only a lower bound for any threshold for arrhythmogenesis.     

ATP-dependent calcium transport in the sarcoplasmic reticulum of the myocardium during vitamin E deficiency in the rat diet

The vitamin E deficiency in the rat diet was studied for its effect on the activity of Ca2+-pump and phosphorylation of sarcoplasmic reticulum membrane fragments of myocardium. It is shown that under such an antioxidant deficiency ATP-dependent accumulation of calcium is 2.5 times as low, from 490 down to 190 nmol/mg of protein for 5 min. The administration of ionol, a synthetic antioxidant, to animals reduces the level of calcium accumulation, it is 1.8 times as high as that with vitamin E deficiency; cAMP-dependent phosphorylation of the sarcoplasmic reticulum preparation membranes of the test animal myocardium produces a 1.6-2.1 times increase in them of the ATP-dependent accumulation of calcium, the kinetics of Ca2+ accumulation is unchanged.