[The effect of K(ATP)-channel activation on the electrical stability of myocardium in rats with postinfarction cardiosclerosis]. / Vliianie aktivatsii K(ATP)-kanalov na élektricheskuiu stabil'nost' miokarda pri postinfarktnom kardioskleroze.

Opening of the ATP-dependent K-channels (K(ATP) channels) upon intravenous administration of the cardioselective activator BMS 180448 (3 mg/kg) decreased the ventricular fibrillation threshold (VFT) in rats with postinfarction cardiosclerosis (PIC). Preliminary injection of the selective K(ATP) channel blocker glibenclamide (0.3 mg/kg, i.v.) completely abolished the profibrillatory effect of BMS 180448. At the same time, the mitochondrial K(ATP) channel blocker 5-hydroxydecanoic acid (5 mg/kg) did not influence the proarrhythmogen activity of BMS 180448. Simultaneous administration of the sarcoK(ATP) channel inhibitor HMR 1098 (3 mg/kg) and BMS 180448 increased the VFT up to a level in intact animals. Administration of the mitoK(ATP) channel activator diazoxide (5 mg/kg) after preliminary treatment with guanethidine (50 mg/kg) increased the VFT in rats with PIC. It is concluded that opening of the mitoK(ATP) channels increases the cardiac electrical stability in rats with PIC.

[Changes in cardiac resistance to arrhythmogenic effects during ATP-dependent K+ channel activation]. / Izmenenie ustoichivosti serdtsa k aritmogennym vozdeistviiam v usloviiakh aktivatsii ATF-zavisimykh K+ kanalov.

It has been found that pretreatment with ATP-dependent potassium channel (KATP-channel) opener, BMS 180448 (3 mg/kg, intravenously), increases cardiac resistance against arrhythmogenic action of coronary artery occlusion and reperfusion in anaesthetized rats. However, BMS 180448 induced a decrease in ventricular fibrillation threshold in rats postinfarction cardiac fibrosis. This effect was completely abolished by administration of the KATP-channel inhibitor, glibenclamide. By contrast, coadministration of BMS 180448 and selective sarcolemmal KATP-channel inhibitor, HMR 1098, promoted an increase in ventricular fibrillation threshold in rats with postinfarction cardiac fibrosis before normal value. The selective mitochondrial KATP-channel opener, diazoxide, also exacerbated a decrease in ventricular fibrillation threshold induced by postinfarction cardiac sclerosis. But after depletion of endogenous catecholamine storage by pretreatment with guanthidine, diazoxide, on the contrary, elevated the ventricular fibrillation threshold. It has been suggested that stimulation of mitochondrial ATP-sensitive potassium channels promotes an elevation in electrical stability of the heart, whereas opening of sarcolemmal KATP-channel increases a possibility of ventricular arrhythmias.

[The role of opiate receptors and ATP-dependent potassium channels of mitochondria in the formation of myocardial adaptive resistance to the arrhythmogenic effect of ischemia and reperfusion]. / Rol' opiatnykh retseptorov i ATF-zavisimykh kalievykh kanalov mitokhondrii v formirovanii adaptatsionnoi ustoichivosti miokarda k aritmogennomu deistviiu ishemii i reperfuzii.

Preliminary stimulation of opiate receptors (ORs) by intravenous administration of mu agonist DALDA (0.5 mg/kg), delta 1 agonist DPDPE (0.5 mg/kg), and kappa agonist (-)-U-50.488 (1 mg/kg) increases rat myocardial resistance to arrhythmogenic effect of coronary occlusion (10 min) and reperfusion (10 min). Activation of delta 2 ORs (DSLET, 0.5 mg/kg) has no effect on the incidence rate of ischemic and reperfusion arrhythmias. Preliminary administration of glibenclamide (0.3 mg/kg), an inhibitor of KATP channels, blocks the antiarrhythmic effect of DALDA and DPDPE. Repeated short-term exposures of rats to immobilization within two weeks increases the heart tolerance to the arrhythmogenic effect of coronary occlusion and reperfusion. This effect disappears after administration of CTAP (0.5 mg/kg), a mu antagonist, or injection of 5-hydroxydecanoate (5 mg/kg), an inhibitor of mitochondrial KATP channels. The selective antagonists of delta and kappa ORs have no effect on cardiac adaptation-induced resistance to the arrhythmogenic effect of ischemia and reperfusion. We believe that stimulation of mu, delta, and kappa ORs increases myocardial tolerance to the arrhythmogenic effect of ischemia and reperfusion through activation of KATP channels. The antiarrhythmic effect of the adaptation is mediated by stimulation of mu ORs and mitochondrial KATP channels.

[Interactions of peripheral mu-opioid receptors and K(ATP)-channels in regulation of cardiac electrical stability in ischemia, reperfusion, and postinfarction cardiosclerosis]. / Vzaimodeistvie perifericheskikh mu-opiatnykh retseptorov i K(ATF)-kanalov v reguliatsii élektricheskoi stabil'nosti serdtsa pri ishemii, reperfuzii i postinfarktnom kardioskleroze.

It has been shown that mu-opioid receptor stimulation by intravenous administration of the selective mu receptor agonist DALDA in a dose of 0.1 mg/kg prevented ischemic and reperfusion arrhythmias in rats subjected to coronary artery occlusion (10 min) and reperfusion (10 min), and also increased the ventricular fibrillation threshold in rats with postinfarction cardiac fibrosis. These effects were abolished by pre-treatment with the selective mu receptor antagonist CTAP in a dose of 0.5 mg/kg or by prior injection of the opioid receptor antagonist naloxone methiodide (2 mg/kg) which does not penetrate the blood-braib barrier. Both antagonists by themselves had no effect on the incidence of occlusion or reperfusion-induced arrhythmias or on the ventricular fibrillation threshold. Pre-treatment with ATP-sensitive K+ channel (KATP channel) blocker glibenclamide in a dose of 0.3 mg/kg completely abolished the antiarrhythmic effect of DALDA. We believe that DALDA prevents occurrence of electrical instability during ischemia and reperfusion and increases the ventricular fibrillation threshold in rats with postinfarction cardiac fibrosis via stimulation of peripheral mu-opioid receptor which appear to be coupled to the KATP channel.

[Stimulation of delta1-opioid receptors increases the ventricular fibrillation threshold in post-infarct cardiosclerosis: the role of K(ATP)-channels]. / Stimuliatsiia del'ta1 opioidnykh retseptorov povyshaet porog zheludochkovoi fibrilliatsii pri postinfarktnom kardioskleroze: rol' K(ATP)-kanalov.

Preliminary administration of the delta 1-opioid receptor (delta 1-OR) selective peptide agonist DPDPE (0.1 mg/kg, i.v.) increased the ventricular fibrillation threshold (VFT) in postinfarction cardiosclerosis in rats. Pretreatment with the selective delta 1-OR antagonists ICI 174,864 (not affecting VFT) in a dose of 0.5 mg/kg completely eliminated the DPDPE-induced increase in the VFT. Pretreatment with the KATP channel selective blocker glibenclamide (0.3 mg/kg, i.v.) completely eliminated the delta 1-OR mediated increase in the VFT protective effect of the delta 1-OR stimulation. The intravenous injection of the mitochondrial KATP channel blocker 5-hydroxydecanoate (5 mg/kg) simultaneously with DPDPE not only eliminated the delta 1-OR mediated increase on VFT, but additionally increased the VBFT drop caused by cardiosclerosis. Injected separately, neither glibenclamide nor hydroxydecanoate affected the VFT level. It is concluded that stimulation of the delta 1-OR increases VFT by activating mitochondrial KATP-channels.

[Myocardial tolerance to arrhythmogenic exposure and pharmacological activation of K(ATP)-channels in rats]. / Tolerantnost' serdtsa krys k aritmogennym vozdeistviiam v usloviiakh farmakologicheskoi aktivatsii K(ATP)-kanalov.

The cardioselective KATP channel activator BMS 180448 (3 mg/kg) administered intravenously 15 min before the coronary artery occlusion (10 min) decreased the incidence of ischemic and reperfusion arrhythmias in rats. A similar antiarrhythmic effect was observed when BMS 180448 was infused 2 min before reperfusion. Pretreatment with BMS 180448 also prevented the occurrence of CsCl induced arrhythmias, but but did not affect the incidence of epinephrine induced arrhythmias. On the contrary, BMS 180448 potentiated the arrhythmogenic action of CaCl2. The mechanism of the antiarrhythmic activity of BMS 180448 is discussed.

[Stimulation of peripheral delta1-opioid receptors as a method of preventing ischemic and reperfusion arrhythmia: role of K(ATP)-channels]. / Stimuliatsiia perifericheskikh delta(1)-opioidnykh retseptorov kak sposob profilaktiki ishemicheskikh i reperfuzionnykh aritmii: rol' K(ATP)-kanalov.

Preliminary administration of the delta 1-opioid receptor (delta 1-OR) peptide agonist DPDPE (0.5 mg/kg, i.v.) decreased the incidence of occlusion (10 min) and reperfusion (10 min) arrhythmias in rats. The delta 2-OR agonist DSLET did not affect arrhythmias upon the coronary artery occlusion and reperfusion. Pretreatment with the selective delta-antagonists ICI 174,864 (2.5 mg/kg) or TIPP[psi] (0.5 mg/kg) completely eliminated the antiarrhythmic effect of DPDPE. Uncapable of crossing the blood brain barrier, the nonselective OR antagonist naloxone methiodide (5 mg/kg) also abolished this effect. At the same time, hexametonium (10 mg/kg) did not antagonize the antiarrhythmic effect of DPDPE. Pretreatment with the KATP channel blocker glibenclamide (0.3 mg/kg) completely eliminated the protective effect of the delta 1-OR stimulation. It was concluded that the delta 1-OR stimulation prevents the ischemic and reperfusion arrhythmias by means of the KATP channel activation.

[Participation of K(ATP)-channels in cardioprotective effect of mu-opioid receptor agonists in acute ischemia and reperfusion of the isolated heart]. / Rol' K(ATP)-kanalov v realizatsii kardioprotektornogo deistviia agonistov miu-opioidnykh retseptorov pri ostroi ishemii i reperfuzii izolirovannogo serdtsa.

Preliminary administration of the mu-opioid receptor (mu-OR) agonist DAMGO (0.1 mg/kg) 15 min before heart isolation led to attenuation of the postischemic systolic and diastolic contractility dysfunction in isolated perfused rat heart. In addition, the mu-OR decreased creatine kinase (CK) release from the heart during the postischemic period, which was indicative of an increase in the sarcolemma tolerance to reperfusion injury. This protective effects are mediated by KATP channel activation. These data show that the mu-OR stimulation in vivo increases, by means of the KATP channel activation, the cardiac tolerance to the ischemia and reperfusion injury in vitro. Pretreatment with mu-OR agonists DAMGO or DALDA in vitro (0.5 mg/liter, 15 min prior to ischemia) exacerbated the postischemic contractility dysfunction of myocardium and did not affect the CK release. It is concluded that the protective effect of mu-OR simulation in vivo is mediated by the activation of these receptors localized outside the heart, probably with an unknown circulating humoral factor.

[Opioid system and cardiac resistance to ischemic and reperfusion injuries]. / Opioidnaia sistema i ustoichvost' serdtsa k povrezhdeniiam pri ishemii-reperfuzii.

In vivo pre-treatment with the opioid receptor antagonist D,L-naloxone completely eliminated the reperfusion-induced creatine kinase (CK) leakage from the rat isolated perfused haert. The inactive isomer L-naloxone decreased the CK release by half. The (-antagonist ICI 174,864 and k-antagonist nor-binanltorphimine exerted a weaker protective effect. The (-antagonist DAMGO, the (2-agonist DSLET, the k1-agonist spiradolin, or the sigma-agonist (+)-SKF 10047, improved myocardial cell viability after ischemia/reperfusion.

[Dependence of the pump function of the isolated rat heart on the functional activity of sigma receptors during reperfusion]. / Zavisimost' nasosnoi funktsii izolirovannogo serdtsa krys ot funktsional'noi aktivnosti sigma-retseptorov v usloviiakh reperfuzii.

Pre-treatment of the sigma-receptor with the sigma-receptor agonist (+)-SKF 10.047 improved the reperfusion recovery of cardiac pump function. The sigma-receptor activation, among other effects, prevented the reperfusion contracture, increased pressure in the left ventricle, and improved survival of cardiomyocytes after ischemia/reperfusion. Pre-treatment with the sigma-receptor antagonist DuP 734 augmented the reperfusion systolic dysfunction of the myocardium and prevented postischemic contractures and cardiac cell lesions. Activation of the cardiac sigma-receptor seems to prompt an augmentation of tolerance to the reperfusion damage.

[mu-Opiate receptor activation and increase in heart resistance to ischemic and reperfusion injury]. / Aktivatsiia mu-opiatnykh retseptorov kak faktor povysheniia ustoichivosti serdtsa k ishemicheskim i reperfuzionnym povrezhdeniiam.

Stimulation of mu-opioid receptors was found to contribute to prevention of myocardial contractile dysfunction and ventricular arrhythmias in ischemia and reperfusion of the rat isolated heart. Endogenous agonists of the mu-opioid receptors were not involved in tonic regulation of the heart resistance against reperfusion disturbances of the rhythm and contractility. On the other hand, mu-opioid receptors are important for development of postischemic contracture.

[The comparative efficacy of emoxipine and sodium oxybutyrate in experimental myocardial ischemia]. / Sravnitel'naia éffektivnost' émoksipina i oksibutirata natriia pri eksperimental'noi ishemii miokarda.

The efficacy of emoxypine (2-ethyl-6-methyl-3-hydroxypyridine chlorohydrate) versus sodium hydroxybutyrate in total and local ischemia followed by reperfusion was studied in the experiments on rat isolated hearts. Emoxypine in a dose of 1 nM in total ischemia was shown to have a protective action, by decreasing reperfusion contracture. In local ischemia, emoxypine, unlike sodium hydroxybutyrate, did not favour greater restoration of the amplitude of isolated heart contractions, but restored coronary flow and stabilized contraction frequency better than did sodium hydroxybutyrate.

[The ammonium chloride modification of the effect of sodium nitroprusside on the contractile activity of guinea pig papillary muscles]. / Modifikatsiia khloridom ammoniia vliianiia nitroprussida natriia na sokratitel'nuiu aktivnost' papilliarnykh myshts morskikh svinok.

The rise of intracellular pH (pH) caused by the replacement of 20 mM NaCl by NH4Cl was shown to enhance guinea-pig papillary muscle contractility while the pH decrease under the NH4Cl abolition from perfusion solution was obtained to reduce the contractile activity. Sodium nitroprusside (SN, 10 microM) does not influence the cardiac muscle contractility in controls but significantly decreases its levels under intracellular alkalinization. SN washout does not restore contractility, hence, the subsequent NH4Cl removal results in contractility increase. In most cases simultaneous action of SN and NH4Cl was accompanied by the development of cardiac mechanical instability. Thus, pHi change can provoke unexpected effects of nitrates.

[The effect of a crown-ether derivative, ethmozine and etatsizin on the functioning of the calcium pools in the guinea pig myocardium]. / Vliianie proizvodnogo kraun-éfira, étmozina i étatsizina na funktsionirovanie kal'tsevykh pulov v miokarde morskikh svinok.

Analysis of the component structure of single contractions of papillary muscles in guinea pigs was used to study the effects of the crown ether derivative benzylase-15-crown-5 and the antiarrhythmic agents ethmozine and ethacizine. The negative inotropic effect of these compounds was shown to be associated with limited penetration of calcium ions from the sarcolemmal pool into cardiac cellular myoplasm.

Investigation of antiischemic properties and mechanism of action of azacrown ether derivative.

The influence of the azacrown ether derivative benzylaza-15-crown-5 on myocardial tolerance to ischemia and on the functional state of the zone of myocardial ischemia during coronary artery occlusion was investigated in experiments on anaesthetized open-chest cats. The compound tested produced a dose-dependent antiischemic effect and prevented the development of myocardial ischemia. In experiments on isolated guinea-pig papillary muscle benzylaza-15-crown-5 inhibited the first and second components of the isoproterenol-induced muscle contraction. The compound decreased the maximal contraction force and had no effect on the cardiac cycle duration and on the time necessary for reaching maximal tension. It is suggested that the protective effect of benzylaza-15-crown-5 during myocardial ischemia is mediated through the inhibition of calcium release from the sarcoplasmic reticulum.

[The use of 2-component myocardial contraction for assessing the mechanism of action of inotropic substances]. / Ispol'zovanie dvukhkomponentnogo sokrashcheniia miokarda dlia otsenki mekhanizme deistviia inotropnykh veshchestv.

The possibility of using two-component contraction of the myocardium to evaluate the mechanisms of action of cardiotropic pharmacological agents was studied. Caffeine, ouabain, low-natrium solution, varapamil, nifedipine and BAY K-8644 were used. It was concluded that the analysis of contraction component amplitude dynamics makes it possible to determine the effect of the pharmacological agents on the interrelated mechanisms of the delivery of Ca2+ into the myoplasm of cardiomyocytes from sarcoplasmic reticulum and through sarcolemma during a single cardiac cycle.

[The effect of trifluoroperazine on cAMP levels in the rat myocardium during various phases of heart cycle]. / Vliianie triftorperazina na soderzhanie cAMP v tkani serdtsa krysy v raznye fazy serdechnogo tsikla.

Trifluoperazine, a calmodulin inhibitor, has been studied for its effect on cAMP content in rat heart tissue at various cardiac cycle stages with beta-adrenoreceptors stimulation by izadrine. When trifluoperazine is absent, the cAMP level is found to be decreased at the beginning of the cardiac cycle in comparison with the middle of the cardiac cycle. Trifluoperazine (6 X 10(-6) M) induces an increase of the content of cyclic nucleotides at the beginning of the cardiac cycle and has no effect on its level in the middle of the cardiac cycle. This leads to a decrease of the difference between cAMP concentrations in the defined cardiac cycle regions. The calmodulin-dependent reactions might be expected to play an important role in the regulation of the myocardium cAMP concentration change during the cardiac cycle.

[Role of Ca-calmodulin- and cAMP-dependent reactions in forming the cardiac cycle]. / Rol' Ca-kal'modulin- i tsAMF-zavisimykh reaktsii v formirovanii serdechnogo tsikla.

The mechanisms of regulation of calcium ion concentration in the heart muscle during cardiac cycle have been considered. A great deal of attention has been devoted to the interaction of Ca2+-calmodulin- and cAMP-dependent reactions in the heart contraction-relaxation processes. The hypothesis on the two-phase structure of cardiac cycle has been proposed. This hypothesis allows to explain some biochemical mechanisms in the positive inotropic effect of catecholamines, cardiac glycosides and caffeine.