Antiarrhythmic activity of <Emphasis Type="Italic">n</Emphasis>-tyrosol during acute myocardial ischemia and reperfusion

Antiarrhythmic activity of n-tyrosol was demonstrated on the model of early occlusion and reperfusion arrhythmia. The preparation reduces the incidence of ventricular tachycardia and fibrillation, increases the percent of animals without ventricular arrhythmia, and moderates the severity of developing ventricular arrhythmias. __________ Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 143, No. 6, pp. 631–633, June, 2007     

Antiarrhythmic properties of a new Suphan-based combined preparation and their possible mechanism of realisation

Considerable potentiation of antiarrhythmic and antifibrilation effects of two cardiotonic agents, Suphan and the Na-channel blocker L1, was found in the model experimentsin vivo with early occlusion and reperfusion arrhythmias. Suphan in combination with L1 inhibited the rise of intracellular Ca²⁺ (by about 70%) in isolated cardiomyocytes incubated under hypoxic conditions. Translated fromByulleten' Eksperimental'noi Biologii I Meditsiny, Vol. 125, No. 1, pp. 59–62, January, 1998     

Effect of biotechnological cytochromec on the early postocclusion and reperfusion arrhythmias

Biotechnological cytochromec showed a lower antiarrhythmic activity in cats with acute occlusion and reperfusion arrhythmias than trimecaine, verapamil, and quaternidine but a higher activity than anapriline. Under experimental conditions, cytochromec potentiated the antiarrhythmic effect of trimecaine and quaternidine. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 127, No. 1, pp. 89–91, January, 1999     

Comparison of antiarrhythmic activities of befol,lidocaine, and bonnecor

The antiarrhythmic activity of befol (an isotoxic dose) is higher than (or comparable to) that of lidocaine and bonnecor in atrial and ventricular arrhythmias induced by acute ischemia, reperfusion, myocardial infarction, or ouabain treatment. In epinephrine-induced arrhythmia, befol is inferior to these drugs (except lidocaine) in activity and range of therapeutic action. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 122, No. 12, pp. 665–668, December, 1996     

Do endogenous ligands of peripheral μ- and δ-opiate receptors mediate antiarrhythmic and cardioprotective effects ofRhodiola rosea?

Oral administration ofRhodiola rosea extract to rats (3.5 ml/kg, 8 days) prevents reperfusion arrhythmias and elicits a protective effect in experiments on isolated heart. Experiments with naloxone and ICI 174,864 suggest that the antiarrhythmic effect ofR. rosea extract is mediated through activation of μ-opiate receptors in the myocardium. The cardioprotective effect of this extract is not associated with opiate receptors. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 124, No. 8, pp. 151–153, August, 1997     

Antiarrhythmic and cardioprotective effect of stimulation of delta1-opiate receptors in myocardial ischemia and reperfusion

Pretreatment with intravenous peptide delta1-opioid receptor (OR) agonist DPDPE (0.5 mg/kg) decreases the incidence of occlusion (10 min) and reperfusion (10 min) arrhythmias in rats. The agonist of delta2-OR DSLET has no effect on arrhythmias in coronary artery occlusion and reperfusion. Pretreatment with selective delta-antagonists ICI 174,864 (2.5 mg/kg) eliminates an antiarrhythmic effect of DPDPE. The addition of DPDPE to the perfusion solution in a final concentration of 0.1 mg/l and/or 0.5 mg/l fifteen min before ischemia also decreases the incidence of reperfusion arrhythmias in a concentration-dependent manner. The addition of DPDPE to the perfusion solution in a final concentration of 0.1 mg/l decreases creatine kinase levels in the coronary sinus effluent. However, DPDPE has no cardioprotective effect in a concentration of 0.5 mg/l or after intravenous administration. It is suggested that antiarrhythmic and cardioprotective effects of DPDPE during reperfusion may be due to stimulation of cardiac delta1-receptors.     

Antiarrhythmic and arrhythmogenic effects of L-carnitine in ischemia and reperfusion

Isolated rat hearts were subjected to 30-min coronary artery occlusion followed by 120-min reperfusion. The hearts (n=8–12) were perfused with Krebs-Henseleit solution enriched with L-carnitine (0.5, 2.5 and 5 mM) for 10 min before and after ischemia or reperfusion and for the whole period of ischemia and reperfusion. Two-hour perfusion with L-carnitine during ischemia/reperfusion markedly (p<0.05) and dose-dependently decreased the incidence of ventricular tachycardia (VT, maximum 65%). The incidence of reperfusion ventricular fibrillation (VF) also decreased from 63% (control) to 17% in hearts perfused with 5 mM L-carnitine, as reflected by a significant (p<0.05) decline in VF duration from 218±99 sec in control to 19±19 sec. Perfusion of etomoxir (palmitoylcarnitinetransferase-1 inhibitor) along with L-carnitine reversed the antiarrhythmogenic action of L-carnitine. Interestingly, short time preischemic administration of L-carnitine produced a concentration-dependent arrhythmogenic effects on both ischemia and reperfusion-induced arrhythmias. These results show that L-carnitine produced a protective effect against reperfusion arrhythmias only when it was perfused for the whole period of the experiment. This protective action was reversed by concomitant use of etomoxir, suggesting that the efficacy of L-carnitine is due to its mitochondrial action but cannot be solely attributed to increased fatty acid oxidation. Translated from Byulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 146, No. 8, pp. 175–178, August, 2008     

Activation of type II cannabinoid receptors improves myocardial tolerance to arrhythmogenic effects of coronary occlusion and reperfusion

Preliminary intravenous injection of cannabinoid receptor agonist HU-210 (0.05 mg/kg) reduced the incidence of ventricular arrhythmias during 10-min coronary occlusion and 10-min reperfusion in chloralose-anesthetized rats. Preliminary injection of type I cannabinoid receptor antagonist SR 141716A (3 mg/kg) had no effect on the antiarrhythmic effect of HU-210, while type II cannabinoid receptor antagonist SR 144528 (1 mg/kg) completely abolished the effect of HU-210. Preconditioning with glibenclamide (0.3 mg/kg), an inhibitor of ATP-dependent K⁺-channels, did not affect the antiarrhythmic activity of HU-210. These findings suggest that antiarrhythmic effect of HU-210 is mediated through activation of type II cannabinoid receptors rather than activation of K⁺-channels.     

Hemodynamic effects of tetrindol in alert normotensive mice and rats after blockade of nitric oxide synthesis

Single intravenous injection of antidepressant tetrindol (1 and 10 mg/kg), a reversible monoamine oxidase A inhibitor, dose-dependently decreased heart rate and mean arterial pressure (in a concentration of 10 mg/kg) in alert NMRI mice and Sprague-Dawley rats. Nitric oxide synthase blockade with L-NAME attenuated tetrindol-induced bradycardia in rats and completely abolished this effect in mice. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 130, No. 8, pp. 193–195, August, 2000     

On the involvement of endogenous μ- and δ-opiate receptor agonists in the antiarrhythmic effect of adaptation

Rats adapted to stress showed a decreased severity and incidence of cardiac arrhythmias induced by epinephrine, and these effects of adaptation were abolished by naloxone. It is suggested that stress adaptation mitigates arrhythmia by activating the endogenous opioid system and stimulating the μ-opiate receptors. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 121, N ^o 1, pp. 24–25, January, 1996 Presented by R. S. Karpov, Member of the Russian Academy of Medical Sciences     

The relationship between mitochondrial respiration and postischemic recovery of isolated heart contractility

Recovery of heart contractility after global normothermic ischemia in New-Zealand rabbits depends on the reperfusion mode and the composition of reperfusion medium and correlates with mitochondrial respiration. Cardiac function can recover also at low ATP concentration (about 1 μmol/g dry tissue). Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 126, No. 11, pp. 538–541, November, 1998     

Melatonin attenuates renal ischemia-reperfusion injury in nitric oxide synthase inhibited rats

Recent studies show that melatonin reduces the blood pressure (BP) and ischemia/reperfusion (I/R)-induced damage. This study was designed to investigate the effects of melatonin on the renal I/R injury in rats given the nitric oxide synthase (NOS) inhibitor, N(omega)-nitro-L-arginine methyl ester (L-NAME). After right nephrectomy, I/R was induced by occlusion of the left renal vessels for 60 min, followed by 24h reperfusion. The administration of melatonin significantly attenuated BP in NOS-inhibited hypertensive rats. Malondialdehyde (MDA) levels, a stable metabolite of the free-radical-mediated lipid peroxidation cascade, were found to be significantly higher in the I/R group (3.48+/-0.2mg/l serum) than in the control group (2.69+/-0.2mg/l serum). L-NAME (40 mgkg(-1) for 15 days)+I/R significantly increased the MDA levels compared to I/R alone. Melatonin administration to L-NAME rats significantly reduced the MDA values resulting from I/R. We also demonstrated that I/R, and especially L-NAME+I/R, lead to structural changes in the kidney and that melatonin attenuates these changes. These results suggest that melatonin reduces BP and I/R injury in NOS inhibited rats by L-NAME.     

Myocardial resistance to ischemic and reperfusion injuries under conditions of chronic administration of opioid receptor agonists and antagonists

Chronic treatment with opioid receptor ligands: nonselective peptide opioid receptor agonist dalargin (intraperitoneally in a dose of 1 mg/kg), selective nonpeptide κ-receptor agonist GR 89696 (subcutaneously in a dose of 0.03 mg/kg), nonselectrive nonpeptide antagonist quadazocine (subcutaneously in a dose of 3 mg/kg) or naltrexone (subcutaneously in a dose of 10 mg/kg) for 20 day had no effect of the incidence of ischemic ventricular arrhythmias and the size of necrotic zone after coronary occlusion and reperfusion in rats in vivo. __________ Translated from Byulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 145, No. 6, pp. 642–644, June, 2008     

Implication of sympathetic innervation of the heart in antiarrhythmic action of intra-atrial laser irradiation

The role of sympathetic nervous system in the antiarrhythmic effect of intra-atrial laser irradiation (λ=632.8 nm) during myocardial ischemia was studied in acute experiments on Nembutal-anesthetized cats. Laser irradiation applied after bilateral, dextral, or sinistral transection of cardiac branches of stellate ganglia increased the number of ischemic rhythm disturbances that developed after occlusion of the circumflex branch of the left coronary artery. The maximum increase in the number of arrhythmias was observed after dextral transection, the occurrence of ventricular fibrillation being 100%. Bilateral transection provoked a larger number of ischemic rhythm disturbances than the sinistral transection. It is probable that the development of the antiarrhythmic effect of laser irradiation requires sustained sympathetic activity targeted at the nonischemic regions in the myocardium that could play a stabilizing role during local ischemic damage to the heart. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 126, No. 11, pp. 522–526, November, 1998     

Hemodilution with liposome-encapsulated low-oxygen-affinity hemoglobin does not attenuate hypothermic cerebral ischemia in rats

Hypothermia decreases cerebral metabolism and increases hemoglobin oxygen affinity. A hypothesis that the reversal of increased oxygen affinity would further attenuate hypothermic cerebral ischemia was tested by evaluating the effects of liposome-encapsulated hemoglobin (LipoHb) with low oxygen affinity (P₅₀ = 40–50 mmHg) on hypothermic incomplete cerebral ischemia. Wistar rats were randomly assigned to one of the following two groups: (A) exchange transfusion with LipoHb solution (Hb = 6 g/dl) (LipoHb, n = 5), (B) no exchange transfusion (control, n = 5). After surface cooling to 22°C, forebrain ischemia was induced for 15 min by bilateral carotid artery occlusion combined with a decrease in the mean arterial pressure (MAP) to 40 mmHg. ³¹P-magnetic resonance spectroscopy was performed during ischemia and 45 min of reperfusion. After reperfusion, MAP was significantly higher in the control group than in the LipoHb group (P < 0.01), although there were no significant differences during ischemia. Intracellular pH and phosphocreatine (PCr) levels decreased during ischemia and returned to the preischemic level in both groups following reperfusion. The LipoHb group had a significantly larger decrease and smaller recovery in PCr than the control group (P < 0.0001). Althouth β-adenosine triphosphate decreased during ischemia in the LipoHb group, it increased in the control group (P < 0.0001). Inorganic phosphate (Pi) increased during ischemia and decreased to the normal value after reperfusion. The LipoHb group experienced a significantly larger production of Pi than the control group (P = 0.02). Hemodilution with high-P₅₀ LipoHb does not reduce ischemic energy depletion induced by hypothermic incomplete forebrain ischemia in rats.     

Effect of in vivo and in vitro stimulation of delta1-opioid receptors on myocardial resistance to arrhythmogenic action of ischemia and reperfusion

Preliminary intravenous injection of peptide agonist of delta1-opioid receptors DPDPE (0.5 mg/kg) decreased the incidence of occlusion (10 min) and reperfusion (10 min) arrhythmias in rats. By contrast, ₂-opioid receptor agonist DSLET produced no effect on the incidence of arrhythmias provoked by coronary occlusion and reperfusion. Preliminary injection of selective -receptor antagonist ICI 174,864 (2.5 mg/kg) or TIPP[] (0.5 mg/kg) completely abolished the antiarrhythmic effect of DPDPE. Stimulation of cardiac ₁-opioid receptors with DPDPE added to perfusion saline in concentrations of 0.1 and 0.5 mg/liter decreased the incidence of reperfusion arrhythmias. Addition of DPDPE to perfusion saline in a concentration of 0.1 mg/liter prevented reoxygenation destruction of cardiomyocytes. By contrast, no cardioprotective effect of this peptide was observed at a concentration of 0.5 mg/liter in perfusion saline or when it was injected intravenously. It is concluded that the cardioprotective and antiarrhythmic effects of DPDPE are caused by activation of cardiac ₁-opioid receptors.     

Cytotoxic effect of low-density lipoproteins on intact, ischemic, and reperfused endothelial cells

The cytotoxic effect of low-density lipoproteins on cultured human umbilical vein endothelial cells increases with their concentration, degree of oxidation, and incubation time, being more pronounced in ischemia or ischemia+reperfusion than in aerobic conditions. Synergism of the cytotoxic effect of lipoproteins with the damaging effect of ischemia and reperfusion promotes the development of atherosclerotic lesions of the vascular wall at sites predisposed to the damage by the ischemia/reperfusion. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 126, No. 9, pp. 302–306, September, 1998     

Antiarrhythmic Activity of Phytoadaptogens in Short-Term Ischemia-Reperfusion of the Heart and Postinfarction Cardiosclerosis

A course of treatment (16 mg/kg orally during 5 days) by Aralia mandshurica or Rhodiola rosea extracts reduced the incidence of ischemic and reperfusion ventricular arrhythmias during 10-min ischemia and 10-min reperfusion. Extracts of Eleutherococcus senticosus, Leuzea carthamoides, and Panax ginseng did not change the incidence of ischemic and reperfusion arrhythmias. Chronic treatment by aralia, rhodiola, and eleutherococcus elevated the ventricular fibrillation threshold in rats with postinfarction cardiosclerosis. Ginseng and leuzea did not change this parameter in rats with postinfarction cardiosclerosis. Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 147, No. 3, pp. 303–306, March, 2009     

Central opioid receptors in the pathogenesis of adrenal arrhythmias

The effect of intraventricular administration of opioid peptides on the frequency and severity of ventricular arrhythmias is studied after intravenous injection of epinephrine. It is found that the selective μ-agonist DAGO and the nonselective σ-agonist DADLE decrease the frequency and severity of arrhythmias. On the other hand, the selective σ-agonist DSLET and the κ-agonist dinorphine A 1–13 potentiate adrenal arrhythmias. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 118, N ^o 9, pp. 241–243, September, 1994 Presented by R. S. Karpov, Member of the Russian Academy of Medical Sciences