RESUMO
Coronary occlusion (45 min) and reperfusion (120 min) in male Wistar rats in vivo, as well as total ischemia (45 min) of an isolated rat heart followed by reperfusion (30 min) were reproduced. The selective δ2-opioid receptor agonist deltorphin II (0.12 mg/kg and 152 nmol/liter) was administered intravenously 5 min before reperfusion in vivo or added to the perfusion solution at the beginning of reperfusion of the isolated heart. The peripheral opioid receptor antagonist naloxone methiodide and δ2-opioid receptor antagonist naltriben were used in doses of 5 and 0.3 mg/kg, respectively. It was found that the infarct-limiting effect of deltorphin II is associated with the activation of δ2-opioid receptors. We have demonstrated that deltorphin II can improve the recovery of the contractility of the isolated heart after total ischemia.
Assuntos
Traumatismo por Reperfusão Miocárdica , Receptores Opioides delta , Animais , Masculino , Ratos , Coração/efeitos dos fármacos , Contração Miocárdica/efeitos dos fármacos , Infarto do Miocárdio/metabolismo , Infarto do Miocárdio/fisiopatologia , Infarto do Miocárdio/tratamento farmacológico , Traumatismo por Reperfusão Miocárdica/metabolismo , Traumatismo por Reperfusão Miocárdica/fisiopatologia , Miocárdio/metabolismo , Antagonistas de Entorpecentes/farmacologia , Oligopeptídeos/farmacologia , Ratos Wistar , Receptores Opioides delta/agonistas , Receptores Opioides delta/metabolismoRESUMO
A comparative analysis of the infarct-limiting activity of δ- and κ-opioid receptors (OR) agonists was carried out on a model of coronary occlusion (45 min) and reperfusion (120 min) in male Wistar rats. We used selective δ2-OR agonist deltorphin II (0.12 mg/kg), δ-OR agonists BW373U86 and p-Cl-Phe DPDPE (0.1 and 1 mg/kg), selective agonists of δ1-OR DPDPE (0.1 and 0.969 mg/kg), κ1-OR U-50,488 (0.1 and 1 mg/kg), κ2-OR GR-89696 (0.1 mg/kg), and κ-OR ICI-199,441 (0.1 mg/kg). All drugs were administered intravenously 5 min before reperfusion. Deltorphin II, BW373U86 (1 mg/kg), p-Cl-Phe DPDPE (1 mg/kg), U-50,488 (1 mg/kg), and ICI-199,441 had a cardioprotective effect. The most promising compounds for drug development are ICI-199,441 and deltorphin II.
Assuntos
Benzamidas , Reperfusão Miocárdica , Piperazinas , Receptores Opioides delta , Ratos , Animais , Masculino , Ratos Wistar , D-Penicilina (2,5)-Encefalina , InfartoRESUMO
The cardioprotective and inotropic effects of standardized active natural substance based on high-molecular-weight compounds of humic origin were studied on the model of global ischemia (40 min) and reperfusion of isolated perfused rat heart. Preventive administration of the test substance (0.1 mg/ml) before ischemia/reperfusion modeling reduced reperfusion contracture and necrotic death of cardiomyocytes and promoted recovery of myocardial contractility. Blockade of NO synthase with L-NAME (100 µM) abolished the above effects of the test substance. It was hypothesized that NO synthase plays an important role in the development of the cardioprotective and inotropic effects of the test natural substance.
Assuntos
Isquemia/metabolismo , Traumatismo por Reperfusão Miocárdica/metabolismo , Miocárdio/metabolismo , Óxido Nítrico Sintase/metabolismo , Animais , Coração , Substâncias Húmicas , Isquemia/genética , Masculino , Traumatismo por Reperfusão Miocárdica/genética , NG-Nitroarginina Metil Éster/metabolismo , Óxido Nítrico Sintase/genética , Ratos , Ratos WistarRESUMO
The active ingredient extracted from the peat humic substances was characterized by physicochemical parameters evaluated by UV- and IR-spectroscopy, titration, and elemental (C, H, N) analysis. The cardiovascular effects of this ingredient were examined on isolated Langendorff-perfused rat heart. It was found that the active substance in a concentration range of 0.01-0.1 mg/ml produced a vasodilating effect; in addition, it decreased the end-diastolic and left-ventricular developed pressures.
Assuntos
Coração/efeitos dos fármacos , Substâncias Húmicas , Vasodilatadores/farmacologia , Animais , Ratos , Ratos Wistar , Solo , Espectrofotometria Ultravioleta , Vasodilatadores/químicaRESUMO
Intravenous injection of nonselective antagonists of opioid receptors (OR) naltrexone (5 mg/kg) and naloxone methiodide (5 mg/kg), selective δ1-OR antagonist BNTX (0.7 mg/kg), selective δ2-OR blocker naltriben (0.3 mg/kg), selective κ-OR antagonist norbinaltorphimine (2 mg/kg), and selective blocker of ORL1 opioid receptors JTC-801 (0.1 mg/kg) produced no effect on reperfusion injury to the heart in rats narcotized with α-chloralose. In contrast, selective µ-OR antagonist CTAP (1 mg/kg) limited the infarct size, although this effect was not observed at a lower CTAP concentration of 0.1 mg/kg. Probably, the myocardial infarct size-limiting effect of CTAP was associated with activation of the non-opioid receptors. It was hypothesized that endogenous OR agonists did not affect heart resistance to reperfusion injury in unadapted rats.
Assuntos
Traumatismo por Reperfusão Miocárdica/metabolismo , Receptores Opioides/fisiologia , Analgésicos Opioides/farmacologia , Animais , Cardiotônicos/farmacologia , Resistência à Doença , Frequência Cardíaca , Masculino , Miocárdio/patologia , Antagonistas de Entorpecentes/farmacologia , Fragmentos de Peptídeos/farmacologia , Fragmentos de Peptídeos/fisiologia , Fatores de Proteção , Ratos Wistar , Somatostatina/farmacologia , Somatostatina/fisiologiaRESUMO
Experiments on isolated perfused rat heart modeled 45-min global ischemia followed by 30-min reperfusion. Ischemic postconditioning was modeled by 3 cycles of reperfusion (30 sec) and ischemia (30 sec). Cardiomyocyte necrosis was assessed by the level of creatine phosphokinase in the perfusate. Postconditioning reduced the release of creatine phosphokinase from the heart by 30%. The cardioprotective effect of ischemic postconditioning was eliminated after inhibition of protein kinase C with cheleritrin or after blockade of δ-isoform of protein kinase C with rottlerin. These findings attest to participation of protein kinase C-δ in the realization of the cardioprotective effect of postconditioning.
Assuntos
Miócitos Cardíacos/enzimologia , Proteína Quinase C-delta/metabolismo , Acetofenonas/farmacologia , Animais , Benzopiranos/farmacologia , Creatina Quinase/metabolismo , Pós-Condicionamento Isquêmico , Precondicionamento Isquêmico Miocárdico , Masculino , Proteína Quinase C-delta/antagonistas & inibidores , Ratos , Ratos WistarRESUMO
CB receptor agonist HU-210 exhibits an infarction-limiting effect during in vitro reperfusion of the heart after focal ischemia. This effect is paralleled by a decrease in left-ventricular developed pressure and double product. In addition, HU-210 reduces end-diastolic pressure during the reperfusion period, which indirectly attests to reduced Ca2+ overload of cardiomyocytes.
Assuntos
Arritmias Cardíacas/tratamento farmacológico , Dronabinol/análogos & derivados , Antagonistas de Aminoácidos Excitatórios/farmacologia , Traumatismo por Reperfusão Miocárdica/tratamento farmacológico , Fármacos Neuroprotetores/farmacologia , Animais , Arritmias Cardíacas/metabolismo , Arritmias Cardíacas/fisiopatologia , Pressão Sanguínea/efeitos dos fármacos , Cálcio/metabolismo , Oclusão Coronária , Vasos Coronários/cirurgia , Dronabinol/farmacologia , Frequência Cardíaca/efeitos dos fármacos , Pós-Condicionamento Isquêmico , Masculino , Traumatismo por Reperfusão Miocárdica/metabolismo , Traumatismo por Reperfusão Miocárdica/fisiopatologia , Miocárdio/metabolismo , Miocárdio/patologia , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Técnicas de Cultura de Órgãos , Ratos , Ratos Wistar , Receptores de Canabinoides/metabolismo , Pressão Ventricular/efeitos dos fármacosRESUMO
We studied the effects of µ-opioid receptor activation in vivo and in vitro on the tolerance of isolated perfused rat heart to global ischemia (45 min) and reperfusion (30 min). Stimulation of µ-receptors in vivo by intraperitoneal administration of µ-opioid receptor agonist DAMGO (0.1 mg/kg) reduced reperfusion release of creatinine phosphokinase and promoted aggravation of postischemic systolic and diastolic dysfunction of the isolated heart. Activation of µ-opioid receptors in vitro by addition of selective agonist DAMGO in a concentration of 170 nM to perfusion solution had no effect on necrotic death of cardiomyocytes and aggravated reperfusion stunning of the heart.
Assuntos
Ala(2)-MePhe(4)-Gly(5)-Encefalina/farmacologia , Contração Miocárdica/efeitos dos fármacos , Isquemia Miocárdica , Traumatismo por Reperfusão Miocárdica , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/patologia , Animais , Morte Celular/efeitos dos fármacos , Ala(2)-MePhe(4)-Gly(5)-Encefalina/uso terapêutico , Coração/efeitos dos fármacos , Coração/fisiologia , Masculino , Isquemia Miocárdica/patologia , Isquemia Miocárdica/fisiopatologia , Traumatismo por Reperfusão Miocárdica/patologia , Traumatismo por Reperfusão Miocárdica/fisiopatologia , Miocárdio/patologia , Necrose , Técnicas de Cultura de Órgãos , Ratos , Ratos Wistar , Receptores Opioides mu/agonistas , ReperfusãoRESUMO
Bradykinin level is increased in myocardium in response to short-term ischemia/reperfusion that is one of the evidences of its trigger role in ischemic preconditioning (IP). Pharmacological induced increase of endogenous bradykinin and kallidin-like peptide levels in myocardium enhances cardiac tolerance to impact of ischemia/reperfusion. Experiments with genetically modified mice indicate that kinins are involved in preconditioning but they are not the only trigger of IP. The B2-receptor blocking abolishes antiarrhythmic, infarct reducing effects ofpreconditioning, eliminates IP-induced cardiac tolerance to oxidative stress. Exogenous bradykinin mimics inotropic and cardioprotective effects of IP but does not mimic antiarrhythmic effect of preconditioning. The intracoronary or intravenous bradykinin infusion enhances human heart resistance to ischemia/reperfusion. Implementation of the cardioprotective effect of IP is provided by the activation of multiple signaling pathways that involve: B2-receptor, calcitonin gene-related peptide, NO-synthase, guanylyl cyclase, cGMP, protein kinase G, mitochondrial KATP channels, reactive oxygen species, kinases C, ERK andAkt. To increase of the human heart tolerance to ischemia/reperfusion is necessary to develop B2-receptor agonists devoid hypotensive and pro-inflammatory properties.
Assuntos
Bradicinina/farmacocinética , Procedimentos Cirúrgicos Cardíacos/métodos , Precondicionamento Isquêmico/métodos , Isquemia Miocárdica/terapia , Miocárdio/metabolismo , Estresse Oxidativo , Animais , Humanos , Período Intraoperatório , Isquemia Miocárdica/metabolismo , Vasodilatadores/farmacocinéticaRESUMO
Parameters of respiration, transmembrane potential, and Ca(2+)-binding capacity of mitochondria isolated from Langendorff-perfused hearts of rats adapted to normobaric hypoxia were analyzed. Ischemia and reperfusion modeling in intact and adapted animals reduced Ca(2+)-binding capacity of mitochondria, which indicated increased sensitivity of mitochondrial permeability transition pores (MPTP) to calcium ions. These changes were accompanied by a decrease in transmembrane potential, ADP/O coefficient (ratio of added ADP to oxygen consumption in State 3), and inhibition of State 3 respiration. At the same time, adaptation attenuated the negative effect of ischemia and reperfusion on the functional state of mitochondria.
Assuntos
Mitocôndrias Cardíacas/metabolismo , Traumatismo por Reperfusão Miocárdica/metabolismo , Adaptação Fisiológica , Animais , Cálcio/metabolismo , Hipóxia/fisiopatologia , Masculino , Potencial da Membrana Mitocondrial , Proteínas de Transporte da Membrana Mitocondrial/metabolismo , Poro de Transição de Permeabilidade Mitocondrial , Consumo de Oxigênio , Ratos WistarRESUMO
Habitation within the polar circle increases cardiovascular mortality rate and particularly increases mortality as a result of coronary events. The main reason of elevation of mortality from these diseases is a dyslipidemia which developed more among alien population residing long time in Far North. Dyslipidemia is less found among aboriginal population of Arctic Circle keeping traditional way of life and respectively it is low rate of mortality from coronary heart disease. The data showed that low rate of dyslipidemia among aboriginal population of North regions depends on fish consumption which is high content of Ω3-polyunsaturated fatty acids.
Assuntos
Doenças Cardiovasculares , Dislipidemias , Ácidos Graxos Ômega-3/farmacologia , Comportamento Alimentar/etnologia , Grupos Populacionais/estatística & dados numéricos , Migrantes/estatística & dados numéricos , Adulto , Regiões Árticas/epidemiologia , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/mortalidade , Doenças Cardiovasculares/fisiopatologia , Temperatura Baixa/efeitos adversos , Dislipidemias/complicações , Dislipidemias/etnologia , Dislipidemias/prevenção & controle , Feminino , Produtos Pesqueiros , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Federação Russa/epidemiologia , TempoRESUMO
In Russia inhospital lethality after acute myocardial infarction is 16.5-16.7%. The part of patients perishes even after recanalisation of infarct-related coronary artery as a result of reperfusion cardiac injury. Experimental data indicate that adenosine receptor agonists and opioids can prevent reperfusion damages of heart that is mimic postconditioning phenomena. Data of clinical observation show that adenosine during intravenous infusion or intracoronary administration during thrombolysis or percutaneous coronary intervention exert infarct reducing effect and eliminate manifestation of of "no-reflow" phenomenon. Clinical data indicate that morphine is able to prevent cardiac reperfusion injury in human. Thus, analysis of published data testifies that adenosine and opioid receptor agonists can be prototype for development of drugs for prophylaxis of reperfusion heart injury.
Assuntos
Adenosina/farmacologia , Analgésicos Opioides/farmacologia , Infarto do Miocárdio/terapia , Traumatismo por Reperfusão Miocárdica , Descoberta de Drogas , Humanos , Reperfusão Miocárdica/efeitos adversos , Traumatismo por Reperfusão Miocárdica/metabolismo , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Receptores Opioides/agonistas , Receptores Opioides/metabolismo , Receptores Purinérgicos P1/metabolismoRESUMO
Authors analyzed articles that opioids may aggravate ischemic and reperfusion damages of the heart but the opioid receptor antagonists may prevent these damages. Authors concluded the it is existed opioid receptor pool an activation of its decreases cardiac tolerance to an impact of ischemia-reperfusion.
Assuntos
Analgésicos Opioides/farmacologia , Traumatismo por Reperfusão Miocárdica/metabolismo , Antagonistas de Entorpecentes/farmacologia , Receptores Opioides/agonistas , Animais , Coração/efeitos dos fármacos , Humanos , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Antagonistas de Entorpecentes/uso terapêutico , Receptores Opioides/metabolismoRESUMO
Irreversible cardiomyocyte damage was induced by 45-min global ischemia followed by 30-min reperfusion in Langendorff-perfused isolated rat heart. Cell damage was assessed by the release of creatine phosphokinase into the perfusate. The hearts were subjected to the following postconditioning protocols: 1) three cycles of 10-sec reperfusion and 10-sec ischemia, total cycle time 20 sec; 2) six cycles of 10-sec reperfusion and 10-sec ischemia, total cycle time 20 sec; 3) three sessions of 20-sec reperfusion and 20-sec ischemia, total cycle time 40 sec; 4) 6 cycles of 20-sec reperfusion and 20-sec ischemia, total cycle time 40 sec; 5) 3 cycles of 30-sec reperfusion and 30-sec ischemia, total cycle time 60 sec. It was found that only postconditioning with a total cycle time of 40 sec or 60 sec prevents myocardial reperfusion injury.
Assuntos
Coração/fisiopatologia , Pós-Condicionamento Isquêmico/métodos , Animais , Técnicas In Vitro , Precondicionamento Isquêmico Miocárdico , Masculino , Traumatismo por Reperfusão Miocárdica/fisiopatologia , Ratos , Ratos WistarRESUMO
The effects of global ischemia (45 min) and reperfusion (30 min) on left-ventricular developed pressure (LVDP), HR, and end-diastolic pressure were studied on isolated perfused rat heart. The following postconditioning protocols were used: 1) 3 cycles of reperfusion (10 sec) and ischemia (10 sec), total cycle duration 20 sec; 2) 6 cycles reperfusion of reperfusion (10 sec) and ischemia (10 sec), total cycle duration 20 sec; 3) 3 cycles of reperfusion (20 sec) and ischemia (20 sec), total cycle duration 40 sec; 4) 6 cycles of reperfusion (20 sec) and ischemia (20 sec), total cycle duration 40 sec; 5) 3 cycles of reperfusion (30 sec) and ischemia (30 sec), total cycle duration 60 sec. The use of several cycles of a total duration of 20 sec had no effect on LVDP, but reduced EDP throughout the reperfusion period. Postconditioning protocol consisting of three 40-sec cycles promoted LVDP recovery during the reperfusion, but had no effect on EDP and decelerated HP normalization. Six 40-sec cycles had no effect on LVDP and EDP, but impeded HR recovery during the reperfusion period. Postconditioning protocol consisting of three 60-sec cycles promoted LVDP increase during the reperfusion and reduced contracture, but these transient effects were accompanied by decelerated HP normalization.
Assuntos
Coração/fisiopatologia , Isquemia/fisiopatologia , Pós-Condicionamento Isquêmico/métodos , Traumatismo por Reperfusão Miocárdica/fisiopatologia , Animais , Pressão Sanguínea , Frequência Cardíaca , Masculino , Contração Miocárdica , Técnicas de Cultura de Órgãos , Ratos , Ratos Wistar , Fatores de Tempo , Pressão VentricularRESUMO
The role of cyclic nucleotides (cAMP, cGMP) and Ca(2+)-ATPase of the sarcoplasmic reticulum in the mechanism of cardioprotective effects of selective δ(1)- and κ(1)-opioid receptor agonists DPDPE and U-50488 was studied under conditions of global ischemia and reperfusion of isolated and perfused rat heart. Activation of both types of opioid receptors 2-fold reduced the reperfusion release of creatine phosphokinase. The cardioprotective effect of U-50488 was paralleled by a 2-fold decrease in cAMP content in the myocardium, while DPDPE did not modify the content of cAMP throughout the experiment. None of these substances changed the content of cGMP in the myocardium. The cardioprotective effect of DPDPE was not observed after inhibition of sarcoplasmic reticulum Ca(2+)-ATPase with cyclopiazonic acid. The cardioprotective effect of U-50488 was associated with reduction of cAMP level in the myocardium, while the cytoprotective effect of DPDPE was mediated by opioidergic modulation of Ca(2+) transport at the level of the sarcoplasmic reticulum.
Assuntos
Cálcio/metabolismo , Nucleotídeos Cíclicos/metabolismo , Receptores Opioides delta/agonistas , Receptores Opioides kappa/agonistas , (trans)-Isômero de 3,4-dicloro-N-metil-N-(2-(1-pirrolidinil)-ciclo-hexil)-benzenoacetamida/farmacologia , Animais , AMP Cíclico/metabolismo , GMP Cíclico/metabolismo , D-Penicilina (2,5)-Encefalina/farmacologia , Coração/efeitos dos fármacos , Indóis/farmacologia , Masculino , Miocárdio/metabolismo , Ratos , Ratos Wistar , Retículo Sarcoplasmático/efeitos dos fármacos , Retículo Sarcoplasmático/metabolismo , ATPases Transportadoras de Cálcio do Retículo Sarcoplasmático/metabolismoRESUMO
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. Hearts from rats adapted to CNH (12 % oxygen) for 3 weeks were extracted, perfused in the Langendorff mode and subjected to 45 min of global ischemia and 30 min of reperfusion. Intervention groups were pretreated for 10 min with antagonists for different OR types: naloxone (300 nmol/l), the selective delta OR antagonist TIPP(psi) (30 nmol/l), the selective delta1 OR antagonist BNTX (1 nmol/l), the selective delta2 OR antagonist naltriben (1 nmol/l), the selective peptide µ OR antagonist CTAP (100 nmol/l) and the selective delta OR antagonist nor-binaltorphimine (3 nmol/l). Creatine kinase activity in coronary effluent and cardiac contractile function were monitored to assess cardiac injury and functional impairment. Additionally, cardiac tissue was collected to measure ATP and to isolate mitochondria to measure respiration rate and calcium retention capacity. Adaptation to CNH decreased myocardial creatine kinase release during reperfusion and improved the postischemic recovery of contractile function. Additionally, CNH improved mitochondrial state 3 and uncoupled respiration rates, ADP/O, mitochondrial transmembrane potential and calcium retention capacity and myocardial ATP level during reperfusion compared to the normoxic group. These protective effects were completely abolished by naloxone, TIPP(psi), naltriben, CTAP but not BNTX or nor-binaltorphimine. These results suggest that cardioprotection associated with adaptation to CNH is mediated by µ and delta2 opioid receptors activation and preservation of mitochondrial function.
Assuntos
Hipóxia/fisiopatologia , Mitocôndrias Cardíacas/fisiologia , Traumatismo por Reperfusão Miocárdica/fisiopatologia , Receptores Opioides delta/fisiologia , Receptores Opioides mu/fisiologia , Animais , Masculino , Mitocôndrias Cardíacas/efeitos dos fármacos , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Antagonistas de Entorpecentes/farmacologia , Técnicas de Cultura de Órgãos , Ratos , Ratos Wistar , Receptores Opioides delta/antagonistas & inibidores , Receptores Opioides mu/antagonistas & inibidoresRESUMO
Remote ischemic preconditioning prevents reperfusion cardiomyocyte apoptosis and has the infarct-limiting effect which is maintained in the experiments on the isolated perfused heart. Remote preconditioning promotes to recovery the contractility of the heart during reperfusion, but did not affect the incidence of occlusion and reperfusion of ventricular arrhythmias. Remote preconditioning has a mild anti-inflammatory effect. Presented article is a review and formulated conclusions based on the published literature data.
Assuntos
Precondicionamento Isquêmico Miocárdico/métodos , Traumatismo por Reperfusão Miocárdica/metabolismo , Miócitos Cardíacos/metabolismo , Animais , Apoptose , Humanos , Contração Miocárdica , Traumatismo por Reperfusão Miocárdica/fisiopatologia , Traumatismo por Reperfusão Miocárdica/terapia , Miócitos Cardíacos/fisiologiaRESUMO
Protein kinase Cepsilon (PKCepsilon) is a target for reactive oxygen species (ROS). It is activated with reaction products of OH* with phospholipids, which presumably include hydroperoxides of fatty acids or alkylperoxy radicals. Activation of PKCs with reactive oxygen species promotes to mito-K(ATP) channel opening and MPT pore (mitochondrial permeability transition pore) closing thereby it is increasing the resistance of cardiomyocytes to hypoxia-reoxygenation. P38 kinase and tyrosine kinases are targets of ROS. Hydroxyl radical or signaling molecules, resulting from its metabolism, may contribute to the activation of p38-kinase that increases the cardiac tolerance to the impact of ischemia-reperfusion. Src tyrosine kinase and P13-kinase apparently are not targets of ROS. The cardioprotective effect of ROS may be due to the activation of transcription factors NFkappaB and CREB.
Assuntos
Precondicionamento Isquêmico Miocárdico , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Proteína Quinase C-épsilon/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Animais , Humanos , Traumatismo por Reperfusão Miocárdica/metabolismo , Transdução de SinaisRESUMO
Reactive oxygen species (ROS) are triggers of ischemic preconditioning (IP). On the role of intracellular messengers of such cardioprotective effect of preconditioning claim: O2*, H2O2, OH*. However, we cannot exclude the possibility that other reactive oxygen metabolites also involved in the IP. Presented data suggest that IP enhances the production of ROS. The source of ROS may be mitochondrial respiratory chain and NADPH oxidase. Exogenous reactive oxygen species (O2*, H2O2) mimic the cardioprotective effect of preconditioning. Preconditioning prevents free radical damage of the heart during ischemia-reperfusion. The protective effect of IP is the consequence of reducing the production of ROS or the result of increased formation of endogenous antioxidants. Antioxidant enzymes are not involved in the protective effect of IP. Cardioprotective effect of many compounds (bradykinin, opioids, acetylcholine, phenylephrine, tumor necrosis factor-α, volatile anesthetics, protonophores, diazoxide, angiotensin II) depends on the increased production of ROS.