Reperfusion Cardiac Injury: Receptors and the Signaling Mechanisms.

It has been documented that Ca overload and increased production of reactive oxygen species play a significant role in reperfusion injury (RI) of cardiomyocytes. Ischemia/reperfusion induces cell death as a result of necrosis, necroptosis, apoptosis, and possibly autophagy, pyroptosis and ferroptosis. It has also been demonstrated that the NLRP3 inflammasome is involved in RI of the heart.

High carbohydrate high fat diet causes arterial hypertension and histological changes in the aortic wall in aged rats: The involvement of connective tissue growth factors and fibronectin.

Background: Age and diabetes are risk factors for arterial hypertension. However, the relationship between age, connective tissue growth factors, vascular aging and arterial hypertension while on a the high-carbohydrate high-fat diet (HCHFD) remains poorly understood.

Purpose: To estimate the relationship between humoral factors, the morphological changes of aorta and impaired blood pressure regulation under the influence of age and a HCHFD.

The role of adrenergic and muscarinic receptors in stress-induced cardiac injury.

Takotsubo syndrome (TS) is a rare but dangerous disease that can be fatal. The pathogenesis of TS is not well understood because there is no animal model of TS that fully mimics TS. It has now been documented that stress exposure (24 h) of rats induced the state which is similar TS in human: contracture damage of myofibrils, elevation of the serum creatine kinase MB level, increased Tc-pyrophosphate (Tc-PYP) accumulation in the heart, QTc interval prolongation, and contractility dysfunction of the heart.

Activation of peripheral δ-opioid receptor prevents reperfusion heart injury.

Coronary artery occlusion (45 min) and reperfusion (2 h) was performed in rats anesthetized with α-chloralose. Opioid receptor agonists were administered intravenously 5 min before reperfusion, while opioid receptor antagonists were administered 10 min before reperfusion. The non-selective opioid δ-receptor agonist DADLE at a dose of 0.

Activation of Peripheral Opioid Kappa1 Receptor Prevents Cardiac Reperfusion Injury.

The role of opioid kappa1 and kappa2 receptors in reperfusion cardiac injury was studied. Male Wistar rats were subjected to a 45-min coronary artery occlusion followed by a 120-min reperfusion. Opioid kappa receptor agonists were administered intravenously 5 min before the onset of reperfusion, while opioid receptor antagonists were given 10 min before reperfusion.

Thyroid hormones and the mechanisms of adaptation to cold.

The thyroid gland plays a crucial role in the regulation of metabolism, oxygen consumption, and the release of energy in the form of heat to maintain the body. Even at rest, these processes are sensitive to changes in thyroid function. This means that along with the adrenergic system, thyroid function determines the organism's ability to adapt to cold.

Takotsubo Syndrome: Clinical Manifestations, Etiology and Pathogenesis.

The purpose of the review is the analysis of clinical and experimental data on the etiology and pathogenesis of takotsubo syndrome (TS). TS is characterized by contractile dysfunction, which usually affects the apical region of the heart without obstruction of coronary artery, moderate increase in myocardial necrosis markers, prolonged QTc interval (in 50% of patients), sometimes elevation of ST segment (in 19% of patients), increase N-Terminal Pro-B-Type Natriuretic Peptide level, microvascular dysfunction, sometimes spasm of the epicardial coronary arteries (in 10% of patients), myocardial edema, and life-threatening ventricular arrhythmias (in 11% of patients). Stress cardiomyopathy is a rare disease, it is observed in 0.

Pharmacology of mitochondrial permeability transition pore inhibitors.

It is now firmly established that an important event in the formation of reperfusion injury of the heart is the opening of mitochondrial permeability transition pores (mPTPs), which changes the permeability of the mitochondria. mPTP opening results in the death of cardiomyocytes through activation of apoptosis and necroptosis. Experimental studies have shown that pharmacological inhibition of mPTP opening promotes the reduction in the infarct size and the suppression of apoptosis.

Effect of Chronic Continuous Normobaric Hypoxia on Functional State of Cardiac Mitochondria and Tolerance of Isolated Rat Heart to Ischemia and Reperfusion: Role of µ and delta2 Opioid Receptors.

Chronic continuous normobaric hypoxia (CNH) increases cardiac tolerance to ischemia/reperfusion injury in vivo and this effect is mediated via µ and delta2 opioid receptors (ORs) activation. CNH has also been shown to be cardioprotective in isolated rat heart. In this study, we hypothesize that this cardioprotective effect of CNH is mediated by activation of µ and delta2 ORs and preservation of mitochondrial function.

Impact of cold adaptation on cardiac tolerance to ischemia/reperfusion and glucocorticoid, thyroid hormone levels.

We have established that the continuous cold exposure (CCE, 4°C, 4 weeks) causes cold adaptation, increases systolic blood pressure, exerts infarct-limiting effect during coronary artery occlusion (45 min) and reperfusion (2 h). The CCE increases adrenal weight, heart weight and triiodothyronine (T3) level but does not change thymus, spleen weight, serum cortisol, corticosterone and thyroxin (T4) levels. The long-term (4°C, 8 h/day, 4 weeks) intermittent cold exposure (LICE) induces adaptation to the cold and increases T4 level.

Cardioprotective properties of opioid receptor agonists in rats with stress-induced cardiac injury.

The objectives of this study were to investigate the role of endogenous opioids in the mediation of stress-induced cardiomyopathy (SIC), and to evaluate which opioid receptors regulate heart resistance to immobilization stress. Wistar rats were subjected to 24 h immobilization stress. Stress-induced heart injury was assessed by 99mTc-pyrophosphate accumulation in the heart.

Physiological and Pathological Role of TRPV1, TRPV2 and TRPV4 Channels in Heart.

Transient receptor potential vanilloid channel 2 (TRPV2) is required for normal cardiac contractility. The stimulation of TRPV1 in isolated cardiomyocytes can aggravate the effect of hypoxia/ reoxygenation (H/R) on H9C2 cells. The knockout of the TRPV1 gene promotes increased tolerance of the isolated perfused heart to the impact of ischemia/reperfusion (I/R).

Trigger, Signaling Mechanism and End Effector of Cardioprotective Effect of Remote Postconditioning of Heart.

The hypothetical trigger of remote postconditioning (RPost) of the heart is the highmolecular weight hydrophobic peptide(s). Nitric oxide and adenosine serve as intermediaries between the peptide and intracellular structures. The role of the autonomic nervous system in RPost requires further study.

Is oxidative stress of adipocytes a cause or a consequence of the metabolic syndrome?

Metabolic syndrome is accompanied by oxidative stress in animals and humans. The main source of ROS in experimental metabolic syndrome is NADPH oxidase and possibly adipocyte mitochondria. It is now documented that oxidative stress induces insulin resistance of adipocytes and increases secretion of leptin, MCP-1, IL-6, and TNF-α by adipocytes.

Role of protein kinase C, PI3 kinase, tyrosine kinases, NO-synthase, KATP channels and MPT pore in the signaling pathway of the cardioprotective effect of chronic continuous hypoxia.

It was established that adaptation to chronic continuous normobaric hypoxia (CCNH) increases cardiac tolerance to ischemia and reperfusion. It was performed coronary artery occlusion (20 min) and reperfusion (3 h) in Wistar rats. CCNH promoted a decrease in the infarct size/area at risk ratio in 2-fold.

Prospects for Creation of Cardioprotective and Antiarrhythmic Drugs Based on Opioid Receptor Agonists.

It has now been demonstrated that the μ, δ1 , δ2 , and κ1 opioid receptor (OR) agonists represent the most promising group of opioids for the creation of drugs enhancing cardiac tolerance to the detrimental effects of ischemia/reperfusion (I/R). Opioids are able to prevent necrosis and apoptosis of cardiomyocytes during I/R and improve cardiac contractility in the reperfusion period. The OR agonists exert an infarct-reducing effect with prophylactic administration and prevent reperfusion-induced cardiomyocyte death when ischemic injury of heart has already occurred; that is, opioids can mimic preconditioning and postconditioning phenomena.

The Effect of CRH, Dexamethasone and Naltrexone on the Mu, Delta and Kappa Opioid Receptor Agonist Binding in Lamb Hypothalamic-Pituitary-Adrenal Axis.

The aim of the study was to evaluate changes in the opioid receptor binding (mu, delta and kappa) in the hypothalamus, anterior pituitary and adrenal cortex (HPA) of lambs treated in vivo with corticotrophin releasing hormone (CRH), naltrexone, an opioid receptor antagonist (NAL), and dexamethasone, a potent cortisol analog (DEX). Experiment was carried out on 3 months old female lambs of polish mountain strain. Lambs received a single i.

Activation of peripheral delta opioid receptors increases cardiac tolerance to arrhythmogenic effect of ischemia/reperfusion.

Objectives: The objective of this study was to investigate the role of peripheral μ, δ1, δ2, and nociceptin opioid receptors agonists in the regulation of cardiac tolerance to the arrhythmogenic effect of ischemia/reperfusion in rats.

Methods: Anesthetized open-chest male Wistar rats were subjected to either 45 minutes of left coronary artery occlusion (phase 1a 10 minutes and phase 2b 35 minutes) and 2 hours of reperfusion in Experiment 1 or 10 minutes of ischemia and 10 minutes of reperfusion in Experiment 2. In Experiment 1, saline or vehicle controls and the mu-specific opioids dermorphin-H (Derm-H) and ([d-Ala2, N-Me-Phe4, Gly-ol5] enkephalin (DAMAGO); the delta-1-specific opioid d-Pen2,5enkephalin (DPDPE); nociceptin; and the delta-2-specific opioids deltorphin-II (Delt-II), Delt-Dvariant (Delt-Dvar), and deltorphin-E (Delt-E) were infused 15 minutes prior to ischemia.

[Preconditioning impact on coronary perfusion during ischemia and reperfusion of heart].

Recent studies have confirmed that ischemic preconditioning prevents appearance of reperfusion endothelial dysfunction. However, the issue of preconditioning impact on no-reflow phenomenon remains unresolved. The receptor mechanisms involved in the cardioprotective and vasoprotective effects of preconditioning are different.

Comparative analysis of the cardioprotective properties of opioid receptor agonists in a rat model of myocardial infarction.

Objectives: This study was conducted to test the hypothesis that opioid receptor (OR)-mediated cardioprotection is agonist specific when administered prior to coronary artery occlusion and reperfusion in a rat model.

Methods: Anesthetized open-chest male Wistar rats were subjected to 45 minutes of left coronary artery occlusion and 2 hours of reperfusion. Opioid agonists were infused 15 minutes prior to coronary artery occlusion.

[Significance of opioid receptors in regulation of cardiac tolerance in pathogenic impact of long-term ischemia-reperfusion in vivo].

The study aimed at investigation of the role of opioid receptor (OR) in regulation of cardiac tolerance to ischemia-reperfusion. Opioid receptor ligands and inhibitors were administered in vivo prior to coronary artery occlusion (45 min) and reperfusion (2 hrs). Occurring infraction size/area at risk (IS/AAR) ratio was determined.

Hibernation-like state induced by an opioid peptide protects against experimental stroke.

Background: Delta opioid peptide [D-ala2,D-leU5]enkephalin (DADLE) induces hibernation in summer ground squirrels, and enhances preservation and survival of isolated or transplanted lungs and hearts. In the present study, we investigated the protective effect of DADLE in the central nervous system.

Results: Adult Sprague-Dawley rats were pretreated with DADLE (4 mg/kg every 2 h x 4 injections, i.

Activation of peripheral delta2 opioid receptors increases cardiac tolerance to ischemia/reperfusion injury Involvement of protein kinase C, NO-synthase, KATP channels and the autonomic nervous system.

Aims: This study aims to investigate the role of peripheral delta(2) opioid receptors in cardiac tolerance to ischemia/reperfusion injury and to examine the contribution of PKC, TK, K(ATP) channels and the autonomic nervous system in delta(2) cardioprotection.

Main Methods: Deltorphin II and various inhibitors were administered in vivo prior to coronary artery occlusion and reperfusion in a rat model. The animals were monitored for the development of arrhythmias, infarct development and the effects of selected inhibitors.

Delta 2-specific opioid receptor agonist and hibernating woodchuck plasma fraction provide ischemic neuroprotection.

Objectives: The authors present evidence that the delta opioid receptor agonist Deltorphin-D(variant) (Delt-D(var)) and hibernating woodchuck plasma (HWP), but not summer-active woodchuck plasma (SAWP), can provide significant neuroprotection from focal ischemia in mice by a mechanism that relies in part on reducing nitric oxide (NO) release in ischemic tissue.

Methods: Cerebral ischemia was produced in wild-type and NO synthase-deficient (NOS(-/-)) mice by transient, 1-hour middle cerebral artery occlusion (MCAO). Behavioral deficits were determined at 22 hours and infarct volume was assessed at 24 hours after MCAO.

Post-treatment with the novel deltorphin E, a delta2-opioid receptor agonist, increases recovery and survival after severe hemorrhagic shock in behaving rats.

Deltorphin E was investigated as a pharmaceutical intervention in the ischemic hemorrhagic model. To monitor the hemodynamic biomarkers mean arterial pressure (MAP) and heart rate (HR) and to facilitate i.v.