Role of Nitric Oxide Synthase in the Infarct-Limiting Effect of Normobaric Hypoxia

Journal of Evolutionary Biochemistry and Physiology - The study was carried out in male Wistar rats. Animals were randomly divided into normoxic control groups and groups exposed to normobaric...     

Amiodarone-Induced Changes in Intracellular Ca2+ Homeostasis in the Atrial Myocardium of Patients with Chronic Coronary Insufficiency

Changes in intracellular Ca²⁺ homeostasis induced by 1 M Amiodarone solution were studied with muscle strips isolated from the right atrial auricles of patients with ischemic heart disease (IHD). The intracellular Ca²⁺ homeostasis was evaluated through the changes in contractility in the muscle strips caused by a 60-s discontinuation of their stimulation by electrical pulses. It was found that, in 30% of the IHD patients, the atrial myocardium displayed an abnormal contractility. Myocardium samples with normal contractility displayed two types of inotropic response to the resumption of electrical stimulation. The first type was associated with a 30% decrease in the parameters of the contraction–relaxation cycle, whereas, for the second type, this decrease was stronger (by 70% or more). An incubation of the muscle samples with the Amiodarone solution suppressed the abnormal contractility, did not affect the muscles with the first type of response, and significantly (p < 0.05) increased the inotropic response in the muscles with the second type of reaction to a short interruption in their electrical stimulation. As Amiodarone itself induces no direct positive inotropic effects, it was supposed that, in some cases of IHD, the presence of Amiodarone in the atrial myocardium is associated with an increased ability of the sarcoplasmic reticulum to retain calcium ions accumulated. This phenomenon may contribute to the suppression of abnormal activity of the atrial myocardium and strengthen the direct antiarrhythmic effect of Amiodarone.     

The regulation of necroptosis and perspectives for the development of new drugs preventing ischemic/reperfusion of cardiac injury

Apoptosis - In the last 10&nbsp;years, mortality from acute myocardial infarction (AMI) has not significantly decreased. This situation is associated with the absence in clinical practice of...     

The Significance of NO-Synthase,Reactive Oxygen Species,Kinases and KATP-Channels in the Development of the Infarct-Limiting Effect of Adaptation to Hypoxia

Journal of Evolutionary Biochemistry and Physiology - The cardioprotective effect of chronic hypoxia (CH) is associated with the activation of inducible nitric oxide synthase (iNOS). Reactive...     

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

Preliminary stimulation of opiate receptors (ORs) by intravenous administration of agonist DALDA (0.5 mg/kg), ₁ agonist DPDPE (0.5 mg/kg), and 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 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 K_ATP 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 antagonist, or injection of 5-hydroxydecanoate (5 mg/kg), an inhibitor of mitochondrial K_ATP channels. The selective antagonists of and ORs have no effect on cardiac adaptation-induced resistance to the arrhythmogenic effect of ischemia and reperfusion. We believe that stimulation of , , and ORs increases myocardial tolerance to the arrhythmogenic effect of ischemia and reperfusion through activation of K_ATP channels. The antiarrhythmic effect of the adaptation is mediated by stimulation of ORs and mitochondrial K_ATP channels.     

Specific features of adaptation of rats to chronic cold treatment

Permanent exposure of rats to four-week cold treatment at +4ºC for 24 h/day resulted in increased weights of the brown adipose tissue, adrenals, and spleen and had no effect on the levels of cortisol and corticosterone in the blood serum. Similar data were observed after exposure of rats to intermittent four-week cold treatment at +4ºC for 8 h/day. After short-term exposure of rats to intermittent cold treatment at +4ºC for 1.5 h/day, all indices studied were similar to those observed in intact animals.     

Ligands for opioid and sigma-receptors improve cardiac electrical stability in rat models of post-infarction cardiosclerosis and stress.

The effects of the extremely selective mu-opioid receptor agonist, [D-Arg2,Lys4]-dermorphin-(1-4)-amide (DALDA), the mu-opioid receptor agonist morphine, the mu/delta agonist D-Ala2, Leu5, Arg6-enkephalin (dalargin), the kappa-opioid receptor agonist spiradoline, and the sigma1-receptor antagonist DuP 734 on ventricular fibrillation threshold (VFT) was investigated in an experimental post-infarction cardiosclerosis model and an immobilization stress-induced model in rats. Both models produced a significant decrease in VFT. The postinfarction cardiosclerosis-induced decrease in VFT was significantly reversed by intravenous administration of dalargin (0.1 mg/kg), DALDA (0.1 mg/kg), or morphine HCl (1.5 mg/kg). Pretreatment with naloxone (0.2 mg/kg) completely eliminated the increase in cardiac electrical stability produced by DALDA. Both spiradoline (8 mg/kg, i.p.) and DuP 734 (1 mg/kg, i.p.) produced a significant increase in VFT in rats with post-infarction cardiosclerosis. This effect of spiradoline was blocked by nor-binaltorphimine. The immobilization stress-induced decrease in VFT was significantly reversed by administration of either DALDA, spiradoline or DuP 734. In conclusion, activation of either mu- or kappa1-opioid receptors or blockade of sigma1-receptors reversed the decrease in VFT in both cardiac compromised models. Since DALDA and dalargin essentially do not cross blood brain barriers, their effects on VFT may be mediated through peripheral mu-opioid receptors.