Ischemic Preconditioning, Myocardial: Exposure of myocardial tissue to brief, repeated periods of vascular occlusion in order to render the myocardium resistant to the deleterious effects of ISCHEMIA or REPERFUSION. The period of pre-exposure and the number of times the tissue is exposed to ischemia and reperfusion vary, the average being 3 to 5 minutes.Myocardial Reperfusion Injury: Damage to the MYOCARDIUM resulting from MYOCARDIAL REPERFUSION (restoration of blood flow to ischemic areas of the HEART.) Reperfusion takes place when there is spontaneous thrombolysis, THROMBOLYTIC THERAPY, collateral flow from other coronary vascular beds, or reversal of vasospasm.Cardiotonic Agents: Agents that have a strengthening effect on the heart or that can increase cardiac output. They may be CARDIAC GLYCOSIDES; SYMPATHOMIMETICS; or other drugs. They are used after MYOCARDIAL INFARCT; CARDIAC SURGICAL PROCEDURES; in SHOCK; or in congestive heart failure (HEART FAILURE).Ischemic Postconditioning: The application of repeated, brief periods of vascular occlusion at the onset of REPERFUSION to reduce REPERFUSION INJURY that follows a prolonged ischemic event. The techniques are similar to ISCHEMIC PRECONDITIONING but the time of application is after the ischemic event instead of before.Myocardium: The muscle tissue of the HEART. It is composed of striated, involuntary muscle cells (MYOCYTES, CARDIAC) connected to form the contractile pump to generate blood flow.Hydroxy Acids: Organic compounds containing both the hydroxyl and carboxyl radicals.Decanoic Acids: 10-carbon saturated monocarboxylic acids.Myocardial Ischemia: A disorder of cardiac function caused by insufficient blood flow to the muscle tissue of the heart. The decreased blood flow may be due to narrowing of the coronary arteries (CORONARY ARTERY DISEASE), to obstruction by a thrombus (CORONARY THROMBOSIS), or less commonly, to diffuse narrowing of arterioles and other small vessels within the heart. Severe interruption of the blood supply to the myocardial tissue may result in necrosis of cardiac muscle (MYOCARDIAL INFARCTION).Mitochondria, Heart: The mitochondria of the myocardium.Myocardial Infarction: NECROSIS of the MYOCARDIUM caused by an obstruction of the blood supply to the heart (CORONARY CIRCULATION).Diazoxide: A benzothiadiazine derivative that is a peripheral vasodilator used for hypertensive emergencies. It lacks diuretic effect, apparently because it lacks a sulfonamide group.Protein Kinase C-epsilon: A protein kinase C subtype that was originally characterized as a CALCIUM-independent, serine-threonine kinase that is activated by PHORBOL ESTERS and DIACYLGLYCEROLS. It is targeted to specific cellular compartments in response to extracellular signals that activate G-PROTEIN-COUPLED RECEPTORS; TYROSINE KINASE RECEPTORS; and intracellular protein tyrosine kinase.Myocytes, Cardiac: Striated muscle cells found in the heart. They are derived from cardiac myoblasts (MYOBLASTS, CARDIAC).Heart: The hollow, muscular organ that maintains the circulation of the blood.Myocardial Reperfusion: Generally, restoration of blood supply to heart tissue which is ischemic due to decrease in normal blood supply. The decrease may result from any source including atherosclerotic obstruction, narrowing of the artery, or surgical clamping. Reperfusion can be induced to treat ischemia. Methods include chemical dissolution of an occluding thrombus, administration of vasodilator drugs, angioplasty, catheterization, and artery bypass graft surgery. However, it is thought that reperfusion can itself further damage the ischemic tissue, causing MYOCARDIAL REPERFUSION INJURY.Ischemic Preconditioning: A technique in which tissue is rendered resistant to the deleterious effects of prolonged ISCHEMIA and REPERFUSION by prior exposure to brief, repeated periods of vascular occlusion. (Am J Physiol 1995 May;268(5 Pt 2):H2063-7, Abstract)Tiopronin: Sulfhydryl acylated derivative of GLYCINE.Rats, Sprague-Dawley: A strain of albino rat used widely for experimental purposes because of its calmness and ease of handling. It was developed by the Sprague-Dawley Animal Company.Benzophenanthridines: Compounds of four rings containing a nitrogen. They are biosynthesized from reticuline via rearrangement of scoulerine. They are similar to BENZYLISOQUINOLINES. Members include chelerythrine and sanguinarine.Mitochondrial Membrane Transport Proteins: Proteins involved in the transport of specific substances across the membranes of the MITOCHONDRIA.PhenanthridinesKATP Channels: Heteromultimers of Kir6 channels (the pore portion) and sulfonylurea receptor (the regulatory portion) which affect function of the HEART; PANCREATIC BETA CELLS; and KIDNEY COLLECTING DUCTS. KATP channel blockers include GLIBENCLAMIDE and mitiglinide whereas openers include CROMAKALIM and minoxidil sulfate.Reperfusion Injury: Adverse functional, metabolic, or structural changes in ischemic tissues resulting from the restoration of blood flow to the tissue (REPERFUSION), including swelling; HEMORRHAGE; NECROSIS; and damage from FREE RADICALS. The most common instance is MYOCARDIAL REPERFUSION INJURY.Receptor, Adenosine A3: A subtype of ADENOSINE RECEPTOR that is found expressed in a variety of locations including the BRAIN and endocrine tissues. The receptor is generally considered to be coupled to the GI, INHIBITORY G-PROTEIN which causes down regulation of CYCLIC AMP.Potassium Channels: Cell membrane glycoproteins that are selectively permeable to potassium ions. At least eight major groups of K channels exist and they are made up of dozens of different subunits.Rats, Wistar: A strain of albino rat developed at the Wistar Institute that has spread widely at other institutions. This has markedly diluted the original strain.Hemodynamics: The movement and the forces involved in the movement of the blood through the CARDIOVASCULAR SYSTEM.Receptors, Opioid, delta: A class of opioid receptors recognized by its pharmacological profile. Delta opioid receptors bind endorphins and enkephalins with approximately equal affinity and have less affinity for dynorphins.Ventricular Function, Left: The hemodynamic and electrophysiological action of the left HEART VENTRICLE. Its measurement is an important aspect of the clinical evaluation of patients with heart disease to determine the effects of the disease on cardiac performance.L-Lactate Dehydrogenase: A tetrameric enzyme that, along with the coenzyme NAD+, catalyzes the interconversion of LACTATE and PYRUVATE. In vertebrates, genes for three different subunits (LDH-A, LDH-B and LDH-C) exist.Cytoprotection: The process by which chemical compounds provide protection to cells against harmful agents.Adenosine: A nucleoside that is composed of ADENINE and D-RIBOSE. Adenosine or adenosine derivatives play many important biological roles in addition to being components of DNA and RNA. Adenosine itself is a neurotransmitter.Cardiovascular Agents: Agents that affect the rate or intensity of cardiac contraction, blood vessel diameter, or blood volume.Signal Transduction: The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.Receptors, Purinergic P1: A class of cell surface receptors that prefer ADENOSINE to other endogenous PURINES. Purinergic P1 receptors are widespread in the body including the cardiovascular, respiratory, immune, and nervous systems. There are at least two pharmacologically distinguishable types (A1 and A2, or Ri and Ra).Ventricular Pressure: The pressure within a CARDIAC VENTRICLE. Ventricular pressure waveforms can be measured in the beating heart by catheterization or estimated using imaging techniques (e.g., DOPPLER ECHOCARDIOGRAPHY). The information is useful in evaluating the function of the MYOCARDIUM; CARDIAC VALVES; and PERICARDIUM, particularly with simultaneous measurement of other (e.g., aortic or atrial) pressures.Myocardial Contraction: Contractile activity of the MYOCARDIUM.Disease Models, Animal: Naturally occurring or experimentally induced animal diseases with pathological processes sufficiently similar to those of human diseases. They are used as study models for human diseases.Reactive Oxygen Species: Molecules or ions formed by the incomplete one-electron reduction of oxygen. These reactive oxygen intermediates include SINGLET OXYGEN; SUPEROXIDES; PEROXIDES; HYDROXYL RADICAL; and HYPOCHLOROUS ACID. They contribute to the microbicidal activity of PHAGOCYTES, regulation of signal transduction and gene expression, and the oxidative damage to NUCLEIC ACIDS; PROTEINS; and LIPIDS.Benzylidene Compounds: Compounds containing the PhCH= radical.Protein Kinase C: An serine-threonine protein kinase that requires the presence of physiological concentrations of CALCIUM and membrane PHOSPHOLIPIDS. The additional presence of DIACYLGLYCEROLS markedly increases its sensitivity to both calcium and phospholipids. The sensitivity of the enzyme can also be increased by PHORBOL ESTERS and it is believed that protein kinase C is the receptor protein of tumor-promoting phorbol esters.Sarcolemma: The excitable plasma membrane of a muscle cell. (Glick, Glossary of Biochemistry and Molecular Biology, 1990)Razoxane: An antimitotic agent with immunosuppressive properties.Cardioplegic Solutions: Solutions which, upon administration, will temporarily arrest cardiac activity. They are used in the performance of heart surgery.Perfusion: Treatment process involving the injection of fluid into an organ or tissue.HSP72 Heat-Shock Proteins: Stress-inducible members of the heat-shock proteins 70 family. HSP72 heat shock proteins function with other MOLECULAR CHAPERONES to mediate PROTEIN FOLDING and to stabilize pre-existent proteins against aggregation.Adenosine A1 Receptor Agonists: Compounds that bind to and stimulate ADENOSINE A1 RECEPTORS.Anesthetics, Inhalation: Gases or volatile liquids that vary in the rate at which they induce anesthesia; potency; the degree of circulation, respiratory, or neuromuscular depression they produce; and analgesic effects. Inhalation anesthetics have advantages over intravenous agents in that the depth of anesthesia can be changed rapidly by altering the inhaled concentration. Because of their rapid elimination, any postoperative respiratory depression is of relatively short duration. (From AMA Drug Evaluations Annual, 1994, p173)Creatine Kinase: A transferase that catalyzes formation of PHOSPHOCREATINE from ATP + CREATINE. The reaction stores ATP energy as phosphocreatine. Three cytoplasmic ISOENZYMES have been identified in human tissues: the MM type from SKELETAL MUSCLE, the MB type from myocardial tissue and the BB type from nervous tissue as well as a mitochondrial isoenzyme. Macro-creatine kinase refers to creatine kinase complexed with other serum proteins.Enzyme Inhibitors: Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.Heart Function Tests: Examinations used to diagnose and treat heart conditions.Glyburide: An antidiabetic sulfonylurea derivative with actions similar to those of chlorpropamide.Physical Conditioning, Animal: Diet modification and physical exercise to improve the ability of animals to perform physical activities.Protective Agents: Synthetic or natural substances which are given to prevent a disease or disorder or are used in the process of treating a disease or injury due to a poisonous agent.Rabbits: The species Oryctolagus cuniculus, in the family Leporidae, order LAGOMORPHA. Rabbits are born in burrows, furless, and with eyes and ears closed. In contrast with HARES, rabbits have 22 chromosome pairs.Glycogen Synthase Kinase 3: A glycogen synthase kinase that was originally described as a key enzyme involved in glycogen metabolism. It regulates a diverse array of functions such as CELL DIVISION, microtubule function and APOPTOSIS.Coronary Circulation: The circulation of blood through the CORONARY VESSELS of the HEART.Nitric Oxide: A free radical gas produced endogenously by a variety of mammalian cells, synthesized from ARGININE by NITRIC OXIDE SYNTHASE. Nitric oxide is one of the ENDOTHELIUM-DEPENDENT RELAXING FACTORS released by the vascular endothelium and mediates VASODILATION. It also inhibits platelet aggregation, induces disaggregation of aggregated platelets, and inhibits platelet adhesion to the vascular endothelium. Nitric oxide activates cytosolic GUANYLATE CYCLASE and thus elevates intracellular levels of CYCLIC GMP.Proto-Oncogene Proteins c-akt: A protein-serine-threonine kinase that is activated by PHOSPHORYLATION in response to GROWTH FACTORS or INSULIN. It plays a major role in cell metabolism, growth, and survival as a core component of SIGNAL TRANSDUCTION. Three isoforms have been described in mammalian cells.Potassium Channel Blockers: A class of drugs that act by inhibition of potassium efflux through cell membranes. Blockade of potassium channels prolongs the duration of ACTION POTENTIALS. They are used as ANTI-ARRHYTHMIA AGENTS and VASODILATOR AGENTS.Time Factors: Elements of limited time intervals, contributing to particular results or situations.Isothiuronium: An undecenyl THIOUREA which may have topical anti-inflammatory activity.Heart Diseases: Pathological conditions involving the HEART including its structural and functional abnormalities.Receptors, Opioid, kappa: A class of opioid receptors recognized by its pharmacological profile. Kappa opioid receptors bind dynorphins with a higher affinity than endorphins which are themselves preferred to enkephalins.Methyl Ethers: A group of compounds that contain the general formula R-OCH3.Receptor, Adenosine A2B: A subclass of adenosine A2 receptors found in the CECUM, the COLON, the BLADDER, and a variety of other tissues. It is generally considered to be a low affinity receptor for ADENOSINE that couples to the GS, STIMULATORY G-PROTEIN.Mice, Knockout: Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes.Adenosine Triphosphate: An adenine nucleotide containing three phosphate groups esterified to the sugar moiety. In addition to its crucial roles in metabolism adenosine triphosphate is a neurotransmitter.Isoflurane: A stable, non-explosive inhalation anesthetic, relatively free from significant side effects.Purinergic P1 Receptor Agonists: Compounds that bind to and stimulate PURINERGIC P1 RECEPTORS.Enzyme Activation: Conversion of an inactive form of an enzyme to one possessing metabolic activity. It includes 1, activation by ions (activators); 2, activation by cofactors (coenzymes); and 3, conversion of an enzyme precursor (proenzyme or zymogen) to an active enzyme.Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.Enzyme Activators: Compounds or factors that act on a specific enzyme to increase its activity.Purinergic P1 Receptor Antagonists: Compounds that bind to and block the stimulation of PURINERGIC P1 RECEPTORS.Apoptosis: One of the mechanisms by which CELL DEATH occurs (compare with NECROSIS and AUTOPHAGOCYTOSIS). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA; (DNA FRAGMENTATION); at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth.Mice, Inbred C57BLHeart Ventricles: The lower right and left chambers of the heart. The right ventricle pumps venous BLOOD into the LUNGS and the left ventricle pumps oxygenated blood into the systemic arterial circulation.Hydrogen Sulfide: A flammable, poisonous gas with a characteristic odor of rotten eggs. It is used in the manufacture of chemicals, in metallurgy, and as an analytical reagent. (From Merck Index, 11th ed)Alkaloids: Organic nitrogenous bases. Many alkaloids of medical importance occur in the animal and vegetable kingdoms, and some have been synthesized. (Grant & Hackh's Chemical Dictionary, 5th ed)S-Nitrosothiols: A group of organic sulfur-containing nitrites, alkyl thionitrites. S-Nitrosothiols include compounds such as S-NITROSO-N-ACETYLPENICILLAMINE and S-NITROSOGLUTATHIONE.Blotting, Western: Identification of proteins or peptides that have been electrophoretically separated by blot transferring from the electrophoresis gel to strips of nitrocellulose paper, followed by labeling with antibody probes.Nitric Oxide Synthase Type III: A CALCIUM-dependent, constitutively-expressed form of nitric oxide synthase found primarily in ENDOTHELIAL CELLS.Protein Kinase C-delta: A ubiquitously expressed protein kinase that is involved in a variety of cellular SIGNAL PATHWAYS. Its activity is regulated by a variety of signaling protein tyrosine kinase.Oxidative Stress: A disturbance in the prooxidant-antioxidant balance in favor of the former, leading to potential damage. Indicators of oxidative stress include damaged DNA bases, protein oxidation products, and lipid peroxidation products (Sies, Oxidative Stress, 1991, pxv-xvi).Naltrexone: Derivative of noroxymorphone that is the N-cyclopropylmethyl congener of NALOXONE. It is a narcotic antagonist that is effective orally, longer lasting and more potent than naloxone, and has been proposed for the treatment of heroin addiction. The FDA has approved naltrexone for the treatment of alcohol dependence.Heart Rate: The number of times the HEART VENTRICLES contract per unit of time, usually per minute.Phosphodiesterase 5 Inhibitors: Compounds that specifically inhibit PHOSPHODIESTERASE 5.Schisandra: A plant genus of the family SCHISANDRACEAE. Members contain schisandrins (Russian) which are also called gomisins (Japanese) or wuweizins (Chinese). The compounds in this genus are very similar to those in the related KADSURA and medicinal usage is very similar. It is sometimes adulterated with KADSURA.Necrosis: The pathological process occurring in cells that are dying from irreparable injuries. It is caused by the progressive, uncontrolled action of degradative ENZYMES, leading to MITOCHONDRIAL SWELLING, nuclear flocculation, and cell lysis. It is distinct it from APOPTOSIS, which is a normal, regulated cellular process.SulfonesNitric Oxide Synthase Type II: A CALCIUM-independent subtype of nitric oxide synthase that may play a role in immune function. It is an inducible enzyme whose expression is transcriptionally regulated by a variety of CYTOKINES.Receptor, Adenosine A1: A subtype of ADENOSINE RECEPTOR that is found expressed in a variety of tissues including the BRAIN and DORSAL HORN NEURONS. The receptor is generally considered to be coupled to the GI, INHIBITORY G-PROTEIN which causes down regulation of CYCLIC AMP.Dose-Response Relationship, Drug: The relationship between the dose of an administered drug and the response of the organism to the drug.Adenosine A3 Receptor Agonists: Drugs that selectively bind to and activate ADENOSINE A3 RECEPTORS.Potassium Channels, Inwardly Rectifying: Potassium channels where the flow of K+ ions into the cell is greater than the outward flow.Cardiotoxins: Agents that have a damaging effect on the HEART. Such damage can occur from ALKYLATING AGENTS; FREE RADICALS; or metabolites from OXIDATIVE STRESS and in some cases is countered by CARDIOTONIC AGENTS. Induction of LONG QT SYNDROME or TORSADES DE POINTES has been the reason for viewing some drugs as cardiotoxins.Enkephalin, Methionine: One of the endogenous pentapeptides with morphine-like activity. It differs from LEU-ENKEPHALIN by the amino acid METHIONINE in position 5. Its first four amino acid sequence is identical to the tetrapeptide sequence at the N-terminal of BETA-ENDORPHIN.Alpha-Amanitin: A cyclic octapeptide with a thioether bridge between the cystine and tryptophan. It inhibits RNA POLYMERASE II. Poisoning may require LIVER TRANSPLANTATION.HSP70 Heat-Shock Proteins: A class of MOLECULAR CHAPERONES found in both prokaryotes and in several compartments of eukaryotic cells. These proteins can interact with polypeptides during a variety of assembly processes in such a way as to prevent the formation of nonfunctional structures.Models, Animal: Non-human animals, selected because of specific characteristics, for use in experimental research, teaching, or testing.Stilbenes: Organic compounds that contain 1,2-diphenylethylene as a functional group.Myocardial Stunning: Prolonged dysfunction of the myocardium after a brief episode of severe ischemia, with gradual return of contractile activity.Narcotic Antagonists: Agents inhibiting the effect of narcotics on the central nervous system.Isoenzymes: Structurally related forms of an enzyme. Each isoenzyme has the same mechanism and classification, but differs in its chemical, physical, or immunological characteristics.Nitrosation: Conversion into nitroso compounds. An example is the reaction of nitrites with amino compounds to form carcinogenic N-nitrosamines.Nicorandil: A derivative of the NIACINAMIDE that is structurally combined with an organic nitrate. It is a potassium-channel opener that causes vasodilatation of arterioles and large coronary arteries. Its nitrate-like properties produce venous vasodilation through stimulation of guanylate cyclase.Heart Arrest, Induced: A procedure to stop the contraction of MYOCARDIUM during HEART SURGERY. It is usually achieved with the use of chemicals (CARDIOPLEGIC SOLUTIONS) or cold temperature (such as chilled perfusate).Mice, Transgenic: Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.Xanthines: Purine bases found in body tissues and fluids and in some plants.Anti-Arrhythmia Agents: Agents used for the treatment or prevention of cardiac arrhythmias. They may affect the polarization-repolarization phase of the action potential, its excitability or refractoriness, or impulse conduction or membrane responsiveness within cardiac fibers. Anti-arrhythmia agents are often classed into four main groups according to their mechanism of action: sodium channel blockade, beta-adrenergic blockade, repolarization prolongation, or calcium channel blockade.Cells, Cultured: Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.Adenosine A2 Receptor Agonists: Compounds that selectively bind to and activate ADENOSINE A2 RECEPTORS.S-Nitroso-N-Acetylpenicillamine: A sulfur-containing alkyl thionitrite that is one of the NITRIC OXIDE DONORS.Antioxidants: Naturally occurring or synthetic substances that inhibit or retard the oxidation of a substance to which it is added. They counteract the harmful and damaging effects of oxidation in animal tissues.HSP27 Heat-Shock Proteins: A subfamily of small heat-shock proteins that function as molecular chaperones that aid in refolding of non-native proteins. They play a protective role that increases cellular survival during times of stress.Myoblasts, Cardiac: Precursor cells destined to differentiate into cardiac myocytes (MYOCYTES, CARDIAC).Phosphatidylinositol 3-Kinases: Phosphotransferases that catalyzes the conversion of 1-phosphatidylinositol to 1-phosphatidylinositol 3-phosphate. Many members of this enzyme class are involved in RECEPTOR MEDIATED SIGNAL TRANSDUCTION and regulation of vesicular transport with the cell. Phosphatidylinositol 3-Kinases have been classified both according to their substrate specificity and their mode of action within the cell.Superoxide Dismutase: An oxidoreductase that catalyzes the reaction between superoxide anions and hydrogen to yield molecular oxygen and hydrogen peroxide. The enzyme protects the cell against dangerous levels of superoxide. EC 1.15.1.1.Nitric Oxide Donors: A diverse group of agents, with unique chemical structures and biochemical requirements, which generate NITRIC OXIDE. These compounds have been used in the treatment of cardiovascular diseases and the management of acute myocardial infarction, acute and chronic congestive heart failure, and surgical control of blood pressure. (Adv Pharmacol 1995;34:361-81)Enkephalin, Leucine-2-Alanine: A delta-selective opioid (ANALGESICS, OPIOID). It can cause transient depression of mean arterial blood pressure and heart rate.Cyclooctanes: A group of compounds with an 8-carbon ring. They may be saturated or unsaturated.Random Allocation: A process involving chance used in therapeutic trials or other research endeavor for allocating experimental subjects, human or animal, between treatment and control groups, or among treatment groups. It may also apply to experiments on inanimate objects.MaleimidesCalcium: A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes.Anoxia: Relatively complete absence of oxygen in one or more tissues.Membrane Potential, Mitochondrial: The voltage difference, normally maintained at approximately -180mV, across the INNER MITOCHONDRIAL MEMBRANE, by a net movement of positive charge across the membrane. It is a major component of the PROTON MOTIVE FORCE in MITOCHONDRIA used to drive the synthesis of ATP.Tocotrienols: Natural analogs of TOCOPHEROLS exhibiting antioxidant activity. These tocol derivatives and isomers contain a benzopyran ring and an unsaturated isoprenoid side chain.Arrhythmias, Cardiac: Any disturbances of the normal rhythmic beating of the heart or MYOCARDIAL CONTRACTION. Cardiac arrhythmias can be classified by the abnormalities in HEART RATE, disorders of electrical impulse generation, or impulse conduction.Nitric Oxide Synthase: An NADPH-dependent enzyme that catalyzes the conversion of L-ARGININE and OXYGEN to produce CITRULLINE and NITRIC OXIDE.Trypan Blue: A diazo-naphthalene sulfonate that is widely used as a stain.STAT3 Transcription Factor: A signal transducer and activator of transcription that mediates cellular responses to INTERLEUKIN-6 family members. STAT3 is constitutively activated in a variety of TUMORS and is a major downstream transducer for the CYTOKINE RECEPTOR GP130.Heme Oxygenase-1: A ubiquitous stress-responsive enzyme that catalyzes the oxidative cleavage of HEME to yield IRON; CARBON MONOXIDE; and BILIVERDIN.Recovery of Function: A partial or complete return to the normal or proper physiologic activity of an organ or part following disease or trauma.Sulfaphenazole: A sulfonilamide anti-infective agent.Guanidines: A family of iminourea derivatives. The parent compound has been isolated from mushrooms, corn germ, rice hulls, mussels, earthworms, and turnip juice. Derivatives may have antiviral and antifungal properties.Mitochondria: Semiautonomous, self-reproducing organelles that occur in the cytoplasm of all cells of most, but not all, eukaryotes. Each mitochondrion is surrounded by a double limiting membrane. The inner membrane is highly invaginated, and its projections are called cristae. Mitochondria are the sites of the reactions of oxidative phosphorylation, which result in the formation of ATP. They contain distinctive RIBOSOMES, transfer RNAs (RNA, TRANSFER); AMINO ACYL T RNA SYNTHETASES; and elongation and termination factors. Mitochondria depend upon genes within the nucleus of the cells in which they reside for many essential messenger RNAs (RNA, MESSENGER). Mitochondria are believed to have arisen from aerobic bacteria that established a symbiotic relationship with primitive protoeukaryotes. (King & Stansfield, A Dictionary of Genetics, 4th ed)Cyclic S-OxidesAldehyde Dehydrogenase: An enzyme that oxidizes an aldehyde in the presence of NAD+ and water to an acid and NADH. This enzyme was formerly classified as EC 1.1.1.70.5'-Nucleotidase: A glycoprotein enzyme present in various organs and in many cells. The enzyme catalyzes the hydrolysis of a 5'-ribonucleotide to a ribonucleoside and orthophosphate in the presence of water. It is cation-dependent and exists in a membrane-bound and soluble form. EC 3.1.3.5.Physiological Processes: The functions and activities of living organisms that support life in single- or multi-cellular organisms from their origin through the progression of life.Heat-Shock Proteins: Proteins which are synthesized in eukaryotic organisms and bacteria in response to hyperthermia and other environmental stresses. They increase thermal tolerance and perform functions essential to cell survival under these conditions.Blood Pressure: PRESSURE of the BLOOD on the ARTERIES and other BLOOD VESSELS.Cardiomegaly: Enlargement of the HEART, usually indicated by a cardiothoracic ratio above 0.50. Heart enlargement may involve the right, the left, or both HEART VENTRICLES or HEART ATRIA. Cardiomegaly is a nonspecific symptom seen in patients with chronic systolic heart failure (HEART FAILURE) or several forms of CARDIOMYOPATHIES.Trimetazidine: A vasodilator used in angina of effort or ischemic heart disease.Ventricular Function: The hemodynamic and electrophysiological action of the HEART VENTRICLES.Coronary Vessels: The veins and arteries of the HEART.p38 Mitogen-Activated Protein Kinases: A mitogen-activated protein kinase subfamily that regulates a variety of cellular processes including CELL GROWTH PROCESSES; CELL DIFFERENTIATION; APOPTOSIS; and cellular responses to INFLAMMATION. The P38 MAP kinases are regulated by CYTOKINE RECEPTORS and can be activated in response to bacterial pathogens.Oncogene Protein v-akt: A viral oncoprotein originally isolated from a murine T CELL LYMPHOMA infected with the acutely transforming retrovirus AKT8. v-akt protein is the viral homologue of PROTO-ONCOGENE PROTEINS C-AKT.8,11,14-Eicosatrienoic Acid: A 20-carbon-chain fatty acid, unsaturated at positions 8, 11, and 14. It differs from arachidonic acid, 5,8,11,14-eicosatetraenoic acid, only at position 5.Receptors, Opioid: Cell membrane proteins that bind opioids and trigger intracellular changes which influence the behavior of cells. The endogenous ligands for opioid receptors in mammals include three families of peptides, the enkephalins, endorphins, and dynorphins. The receptor classes include mu, delta, and kappa receptors. Sigma receptors bind several psychoactive substances, including certain opioids, but their endogenous ligands are not known.Benzamides: BENZOIC ACID amides.Free Radical Scavengers: Substances that influence the course of a chemical reaction by ready combination with free radicals. Among other effects, this combining activity protects pancreatic islets against damage by cytokines and prevents myocardial and pulmonary perfusion injuries.Heat Stress Disorders: A group of conditions that develop due to overexposure or overexertion in excessive environmental heat.Pinacidil: A guanidine that opens POTASSIUM CHANNELS producing direct peripheral vasodilatation of the ARTERIOLES. It reduces BLOOD PRESSURE and peripheral resistance and produces fluid retention. (Martindale The Extra Pharmacopoeia, 31st ed)FlavoproteinsOxidation-Reduction: A chemical reaction in which an electron is transferred from one molecule to another. The electron-donating molecule is the reducing agent or reductant; the electron-accepting molecule is the oxidizing agent or oxidant. Reducing and oxidizing agents function as conjugate reductant-oxidant pairs or redox pairs (Lehninger, Principles of Biochemistry, 1982, p471).Androstadienes: Derivatives of the steroid androstane having two double bonds at any site in any of the rings.Protein Kinase Inhibitors: Agents that inhibit PROTEIN KINASES.Energy Metabolism: The chemical reactions involved in the production and utilization of various forms of energy in cells.Cell Hypoxia: A condition of decreased oxygen content at the cellular level.ChromonesCyclic GMP-Dependent Protein Kinases: A group of cyclic GMP-dependent enzymes that catalyze the phosphorylation of SERINE or THREONINE residues of proteins.Acetylglucosamine: The N-acetyl derivative of glucosamine.Mitochondrial Swelling: An increase in MITOCHONDRIAL VOLUME due to an influx of fluid; it occurs in hypotonic solutions due to osmotic pressure and in isotonic solutions as a result of altered permeability of the membranes of respiring mitochondria.Cell Survival: The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability.Drug Evaluation, Preclinical: Preclinical testing of drugs in experimental animals or in vitro for their biological and toxic effects and potential clinical applications.Animals, Newborn: Refers to animals in the period of time just after birth.Antibiotics, Antineoplastic: Chemical substances, produced by microorganisms, inhibiting or preventing the proliferation of neoplasms.Benzopyrans: Compounds with a core of fused benzo-pyran rings.Creatine Kinase, MB Form: An isoenzyme of creatine kinase found in the CARDIAC MUSCLE.AcetophenonesMitochondrial Proteins: Proteins encoded by the mitochondrial genome or proteins encoded by the nuclear genome that are imported to and resident in the MITOCHONDRIA.Sulfonylurea Receptors: ATP-BINDING CASSETTE PROTEINS that are highly conserved and widely expressed in nature. They form an integral part of the ATP-sensitive potassium channel complex which has two intracellular nucleotide folds that bind to sulfonylureas and their analogs.Up-Regulation: A positive regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins.Adamantane: A tricyclo bridged hydrocarbon.Atractyloside: A glycoside of a kaurene type diterpene that is found in some plants including Atractylis gummifera (ATRACTYLIS); COFFEE; XANTHIUM, and CALLILEPIS. Toxicity is due to inhibition of ADENINE NUCLEOTIDE TRANSLOCASE.Sodium-Hydrogen Antiporter: A plasma membrane exchange glycoprotein transporter that functions in intracellular pH regulation, cell volume regulation, and cellular response to many different hormones and mitogens.Adenosine A1 Receptor Antagonists: Compounds that bind to and block the stimulation of ADENOSINE A1 RECEPTORS.Imidazoles: Compounds containing 1,3-diazole, a five membered aromatic ring containing two nitrogen atoms separated by one of the carbons. Chemically reduced ones include IMIDAZOLINES and IMIDAZOLIDINES. Distinguish from 1,2-diazole (PYRAZOLES).Janus Kinases: A family of intracellular tyrosine kinases that participate in the signaling cascade of cytokines by associating with specific CYTOKINE RECEPTORS. They act upon STAT TRANSCRIPTION FACTORS in signaling pathway referred to as the JAK/STAT pathway. The name Janus kinase refers to the fact the proteins have two phosphate-transferring domains.Ventricular Remodeling: The geometric and structural changes that the HEART VENTRICLES undergo, usually following MYOCARDIAL INFARCTION. It comprises expansion of the infarct and dilatation of the healthy ventricle segments. While most prevalent in the left ventricle, it can also occur in the right ventricle.PiperazinesMorpholinesIndoles: Benzopyrroles with the nitrogen at the number one carbon adjacent to the benzyl portion, in contrast to ISOINDOLES which have the nitrogen away from the six-membered ring.Cyclooxygenase 2: An inducibly-expressed subtype of prostaglandin-endoperoxide synthase. It plays an important role in many cellular processes and INFLAMMATION. It is the target of COX2 INHIBITORS.Mice, Inbred ICRMalondialdehyde: The dialdehyde of malonic acid.Ventricular Dysfunction: A condition in which HEART VENTRICLES exhibit impaired function.QuinolinesAMP-Activated Protein Kinases: Intracellular signaling protein kinases that play a signaling role in the regulation of cellular energy metabolism. Their activity largely depends upon the concentration of cellular AMP which is increased under conditions of low energy or metabolic stress. AMP-activated protein kinases modify enzymes involved in LIPID METABOLISM, which in turn provide substrates needed to convert AMP into ATP.Autophagy: The segregation and degradation of damaged or unwanted cytoplasmic constituents by autophagic vacuoles (cytolysosomes) composed of LYSOSOMES containing cellular components in the process of digestion; it plays an important role in BIOLOGICAL METAMORPHOSIS of amphibians, in the removal of bone by osteoclasts, and in the degradation of normal cell components in nutritional deficiency states.HSP20 Heat-Shock Proteins: A subfamily of small heat-shock proteins that are closely related to ALPHA B-CRYSTALLIN. Hsp20 heat-shock proteins can undergo PHOSPHORYLATION by CYCLIC GMP-DEPENDENT PROTEIN KINASES.Mitochondrial Membranes: The two lipoprotein layers in the MITOCHONDRION. The outer membrane encloses the entire mitochondrion and contains channels with TRANSPORT PROTEINS to move molecules and ions in and out of the organelle. The inner membrane folds into cristae and contains many ENZYMES important to cell METABOLISM and energy production (MITOCHONDRIAL ATP SYNTHASE).Caveolin 3: A caveolin that is expressed exclusively in MUSCLE CELLS and is sufficient to form CAVEOLAE in SARCOLEMMA. Mutations in caveolin 3 are associated with multiple muscle diseases including DISTAL MYOPATHY and LIMB-GIRDLE MUSCULAR DYSTROPHY.Coronary Occlusion: Complete blockage of blood flow through one of the CORONARY ARTERIES, usually from CORONARY ATHEROSCLEROSIS.Mitogen-Activated Protein Kinases: A superfamily of PROTEIN-SERINE-THREONINE KINASES that are activated by diverse stimuli via protein kinase cascades. They are the final components of the cascades, activated by phosphorylation by MITOGEN-ACTIVATED PROTEIN KINASE KINASES, which in turn are activated by mitogen-activated protein kinase kinase kinases (MAP KINASE KINASE KINASES).Protein Transport: The process of moving proteins from one cellular compartment (including extracellular) to another by various sorting and transport mechanisms such as gated transport, protein translocation, and vesicular transport.In Situ Nick-End Labeling: An in situ method for detecting areas of DNA which are nicked during APOPTOSIS. Terminal deoxynucleotidyl transferase is used to add labeled dUTP, in a template-independent manner, to the 3 prime OH ends of either single- or double-stranded DNA. The terminal deoxynucleotidyl transferase nick end labeling, or TUNEL, assay labels apoptosis on a single-cell level, making it more sensitive than agarose gel electrophoresis for analysis of DNA FRAGMENTATION.Reactive Nitrogen Species: Nitrogenous products of NITRIC OXIDE synthases, ranging from NITRIC OXIDE to NITRATES. These reactive nitrogen intermediates also include the inorganic PEROXYNITROUS ACID and the organic S-NITROSOTHIOLS.Phosphatidylinositol 3-Kinase: A phosphatidylinositol 3-kinase that catalyzes the conversion of 1-phosphatidylinositol into 1-phosphatidylinositol 3-phosphate.Thiourea: A photographic fixative used also in the manufacture of resins. According to the Fourth Annual Report on Carcinogens (NTP 85-002, 1985), this substance may reasonably be anticipated to be a carcinogen (Merck Index, 9th ed). Many of its derivatives are ANTITHYROID AGENTS and/or FREE RADICAL SCAVENGERS.
  • Remote ischemic conditioning (RIC) is an experimental medical procedure that aims to reduce the severity of ischaemic injury to an organ such as the heart or the brain, most commonly in the situation of a heart attack or a stroke, or during procedures such as heart surgery when the heart may temporary suffer ischaemia during the operation. (wikipedia.org)
  • In the basic research setting, the HCI was instrumental is identifying the signalling pathways including the RISK pathway as well as the role of the mitochondrial permeability transition pore (MPTP) in cardioprotection. (ucl.ac.uk)
  • En conséquence, le débit sanguin augmente, ce qui entraîne une meilleure endurance, réduit l'effort cardiaque, améliore la circulation, et aide à maintenir la pression artérielle à un niveau désormais normal. (forevergreen.org)
  • Moreover, some of the medications used to treat these risk factors, including statins, nitrates, and antidiabetic drugs, may impact cardioprotection by modifying cellular signaling. (sigmaaldrich.com)
  • These data reveal another essential explanation of cellular transplantation therapy in damage recovery from ischemic stroke and offer new therapeutic possibilities. (eurekaselect.com)
  • This article reviews our current knowledge of the cellular mechanisms responsible for mediation of ischemic preconditioning, the evidence for the existence of this phenomenon in humans, and its potential therapeutic applications. (ucl.ac.uk)
  • In preclinical studies, Nicotinamide Mononucleotide work on mice has proved to be handy in cellular biochemical activities, management of Alzheimer's disease, age-related diabetes, complications that arise from obesity, and cardioprotection. (articlecity.com)