RESUMO
INTRODUCTION: The function of endoplasmic reticulum (ER), a Ca2+ storage compartment and site of protein folding, is altered by disruption of intracellular homeostasis. Misfolded proteins accumulated in the ER lead to ER stress (ERS), unfolded protein response (UPR) activation and ER Ca2+ loss. Myocardial stunning is a temporary contractile dysfunction, which occurs after brief ischemic periods with minimal or no cell death, being oxidative stress and Ca2+ overload potential underlying mechanisms. Myocardial stunning induces ERS response with negatively impact on the post-ischemic mechanical performance through an unknown mechanism. AIMS: In this study, we explored whether ER Ca2+ efflux through the translocon, a major Ca2+ leak channel, contributes to Ca2+ mishandling and the consequent contractile abnormalities of the stunned myocardium. METHODS: Mechanical performance, cytosolic Ca2+, UPR markers and oxidative state were evaluated in perfused rat/mouse hearts subjected to a brief ischemia followed by reperfusion (I/R) in absence or presence of the translocon inhibitor, emetine (1 µM), comparing its effects with those of the chaperones TUDCA (30 µM) and 4-PBA (3 mM). RESULTS: Emetine treatment precluded the I/R-induced increase in UPR signaling markers and improved the contractile recovery together with a remarkable attenuation in myocardial stiffness when compared to I/R hearts with no drug. This alleviation of I/R-induced mechanical abnormalities was more effective than that obtained with the chemical chaperones, TUDCA and 4-PBA. Moreover, emetine treatment produced a striking improvement in diastolic Ca2+ handling with a partial recovery of the I/R-induced oxidative stress. CONCLUSION: Blocking ER Ca2+ store depletion via translocon suppressed ER stress and improved mechanical performance and diastolic Ca2+ handling of stunned myocardium. Modulation of translocon permeability emerges as a therapeutic approach to face dysfunctional consequences of the I/R injury.
Assuntos
Cálcio/metabolismo , Emetina/farmacologia , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Contração Miocárdica , Miocárdio Atordoado , Canais de Translocação SEC/antagonistas & inibidores , Resposta a Proteínas não Dobradas , Animais , Sinalização do Cálcio , Camundongos , Contração Miocárdica/efeitos dos fármacos , Contração Miocárdica/fisiologia , Miocárdio Atordoado/tratamento farmacológico , Miocárdio Atordoado/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Inibidores da Síntese de Proteínas/farmacologia , Ratos , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/prevenção & controle , Resposta a Proteínas não Dobradas/efeitos dos fármacos , Resposta a Proteínas não Dobradas/fisiologiaRESUMO
During ischemia and reperfusion (I/R) mitochondria suffer a deficiency to supply the cardiomyocyte with chemical energy, but also contribute to the cytosolic ionic alterations especially of Ca2+. Their free calcium concentration ([Ca2+]m) mainly depends on mitochondrial entrance through the uniporter (UCam) and extrusion in exchange with Na+ (mNCX) driven by the electrochemical gradient (ΔΨm). Cardiac energetic is frequently estimated by the oxygen consumption, which determines metabolism coupled to ATP production and to the maintaining of ΔΨm. Nevertheless, a better estimation of heart energy consumption is the total heat release associated to ATP hydrolysis, metabolism, and binding reactions, which is measurable either in the presence or the absence of oxygenation or perfusion. Consequently, a mechano-calorimetrical approach on isolated hearts gives a tool to evaluate muscle economy. The mitochondrial role during I/R depends on the injury degree. We investigated the role of the mitochondrial Ca2+ transporters in the energetic of hearts stunned by a model of no-flow I/R in rat hearts. This chapter explores an integrated view of previous and new results which give evidences to the mitochondrial role in cardiac stunning by ischemia o hypoxia, and the influence of thyroid alterations and cardioprotective strategies, such as cardioplegic solutions (high K-low Ca, pyruvate) and the phytoestrogen genistein in both sex. Rat ventricles were perfused in a flow-calorimeter at either 30 °C or 37 °C to continuously measure the left ventricular pressure (LVP) and total heat rate (Ht). A pharmacological treatment was done before exposing to no-flow I and R. The post-ischemic contractile (PICR as %) and energetical (Ht) recovery and muscle economy (Eco: P/Ht) were determined during stunning. The functional interaction between mitochondria (Mit) and sarcoplasmic reticulum (SR) was evaluated with selective mitochondrial inhibitors in hearts reperfused with Krebs-10 mM caffeine-36 mM Na+. The caffeine induced contracture (CIC) was due to SR Ca2+ release, while relaxation mainly depends on mitochondrial Ca2+ uptake since neither SL-NCX nor SERCA are functional under this media. The ratio of area-under-curves over ischemic values (AUC-ΔHt/AUC-ΔLVP) estimates the energetical consumption (EC) to maintain CIC. Relaxation of CIC was accelerated by inhibition of mNCX or by adding the aerobic substrate pyruvate, while both increased EC. Contrarily, relaxation was slowed by cardioplegia (high K-low Ca Krebs) and by inhibition of UCam. Thus, Mit regulate the cytosolic [Ca2+] and SR Ca2+ content. Both, hyperthyroidism (HpT) and hypothyroidism (HypoT) reduced the peak of CIC but increased EC, in spite of improving PICR. Both, CIC and PICR in HpT were also sensitive to inhibition of mNCX or UCam, suggesting that Mit contribute to regulate the SR store and Ca2+ release. The interaction between mitochondria and SR and the energetic consequences were also analyzed for the effects of genistein in hearts exposed to I/R, and for the hypoxia/reoxygenation process. Our results give evidence about the mitochondrial regulation of both PICR and energetic consumption during stunning, through the Ca2+ movement.
Assuntos
Metabolismo Energético , Mitocôndrias Cardíacas/metabolismo , Contração Miocárdica , Traumatismo por Reperfusão Miocárdica/metabolismo , Reperfusão Miocárdica/efeitos adversos , Miocárdio Atordoado/metabolismo , Miócitos Cardíacos/metabolismo , Animais , Sinalização do Cálcio , Circulação Coronária , Humanos , Mitocôndrias Cardíacas/ultraestrutura , Traumatismo por Reperfusão Miocárdica/etiologia , Traumatismo por Reperfusão Miocárdica/patologia , Traumatismo por Reperfusão Miocárdica/fisiopatologia , Miocárdio Atordoado/etiologia , Miocárdio Atordoado/patologia , Miocárdio Atordoado/fisiopatologia , Miócitos Cardíacos/ultraestrutura , Fatores de Risco , Retículo Sarcoplasmático/metabolismo , Fatores de TempoRESUMO
AIM: We evaluated the effect of thioredoxin1 (Trx1) system on postischemic ventricular and mitochondrial dysfunction using transgenic mice overexpressing cardiac Trx1 and a dominant negative (DN-Trx1) mutant (C32S/C35S) of Trx1. Langendorff-perfused hearts were subjected to 15 min of ischemia followed by 30 min of reperfusion (R). We measured left ventricular developed pressure (LVDP, mmHg), left ventricular end diastolic pressure (LVEDP, mmHg), and t63 (relaxation index, msec). Mitochondrial respiration, SERCA2a, phospholamban (PLB), and phospholamban phosphorylation (p-PLB) Thr17 expression (Western blot) were also evaluated. RESULTS: At 30 min of reperfusion, Trx1 improved contractile state (LVDP: Trx1: 57.4 ± 4.9 vs. Wt: 27.1 ± 6.3 and DN-Trx1: 29.2 ± 7.1, p < 0.05); decreased myocardial stiffness (LVEDP: Wt: 24.5 ± 4.8 vs. Trx1: 11.8 ± 2.9, p < 0.05); and improved the isovolumic relaxation (t63: Wt: 63.3 ± 3.2 vs. Trx1: 51.4 ± 1.9, p < 0.05). DN-Trx1 mice aggravated the myocardial stiffness and isovolumic relaxation. Only the expression of p-PLB Thr17 increased at 1.5 min R in Wt and DN-Trx1 groups. At 30 min of reperfusion, state 3 mitochondrial O2 consumption was impaired by 13% in Wt and by 33% in DN-Trx1. ADP/O ratios for Wt and DN-Trx1 decrease by 25% and 28%, respectively; whereas the Trx1 does not change after ischemia and reperfusion (I/R). Interestingly, baseline values of complex I activity were increased in Trx1 mice; they were 24% and 47% higher than in Wt and DN-Trx1 mice, respectively (p < 0.01). INNOVATION AND CONCLUSION: These results strongly suggest that Trx1 ameliorates the myocardial effects of I/R by improving the free radical-mediated damage in cardiac and mitochondrial function, opening the possibility of new therapeutic strategies in coronary artery disease. Antioxid. Redox Signal. 25, 78-88.
Assuntos
Mitocôndrias Cardíacas/metabolismo , Traumatismo por Reperfusão Miocárdica/metabolismo , Traumatismo por Reperfusão Miocárdica/fisiopatologia , Miocárdio Atordoado/metabolismo , Tiorredoxinas/metabolismo , Disfunção Ventricular/metabolismo , Animais , Complexo de Proteínas da Cadeia de Transporte de Elétrons/metabolismo , Peróxido de Hidrogênio/metabolismo , Masculino , Camundongos , Contração Miocárdica , Traumatismo por Reperfusão Miocárdica/genética , Miocárdio Atordoado/genética , Consumo de Oxigênio , Tiorredoxinas/genética , Disfunção Ventricular/genéticaRESUMO
Although the phytoestrogen genistein (Gen) is considered protective in cardiovascular diseases, its direct effects on stunned hearts after transient ischemia-reperfusion (I/R) are unknown. This report studied the effects of 20 µmol/L Gen on the mechano-calorimetric behaviour during I/R of rat and guinea pig hearts to evaluate the energetics of Ca(2+) homeostasis. Isolated beating hearts were perfused with control Krebs solution inside a calorimeter with or without perfusion of Gen before a transient period of I/R. Left ventricular pressure development (P) and total heat rate (Ht) were continuously measured. At 37°C, Gen did not change post-ischemic contractile recovery (PICR), but it increased the relaxation rate. However, PICR was reduced in hearts of male rats and guinea pigs at 30°C. Total muscle economy (P/Ht) showed the same behaviour as P at each temperature. Inhibition of phosphatases with orthovanadate during Gen perfusion prevented a decrease in PICR in male rat hearts, suggesting that this effect is due to tyrosine kinase inhibition. Reperfusing ischemic hearts with 10 mmol/L caffeine-36 mmol/L Na(+)-Krebs induced contracture dependent on the sarcoreticular Ca(2+) content. Contracture relaxation depends on mitochondrial Ca(2+) uptake and Gen reduced the relaxation rate. Moreover, Gen prevented the increase in Rhod-2 fluorescence (free [Ca(2+)]m) of rat cardiomyocytes. In guinea pig hearts, Gen maintained ischemic preconditioning, but was reduced by 5-hydroxydecanoate, suggesting the participation of mitochondrial adenosine triphosphate (ATP)-dependent K channels. Results suggest that Gen acts on several mechanisms that regulate myocardial calcium homeostasis and energetics during I/R, which differ in a temperature- and sex-dependent manner.
Assuntos
Metabolismo Energético/efeitos dos fármacos , Genisteína/farmacologia , Coração/efeitos dos fármacos , Coração/fisiopatologia , Miocárdio Atordoado/metabolismo , Caracteres Sexuais , Animais , Cálcio/metabolismo , Citosol/efeitos dos fármacos , Citosol/metabolismo , Feminino , Cobaias , Masculino , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Contração Miocárdica/efeitos dos fármacos , Miocárdio Atordoado/complicações , Miocárdio Atordoado/patologia , Miocárdio Atordoado/fisiopatologia , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/patologia , Ratos , Traumatismo por Reperfusão/complicações , Pressão Ventricular/efeitos dos fármacosRESUMO
NEW FINDINGS: What is the central question of this study? Hyperthyroidism is a cardiac risk factor, but thyroid therapy is used on myocardial stunning. What is the consequence of hyperthyroidism for mitochondrial metabolism and Ca(2+) handling of the postischaemic stunned heart? What is the main finding and its importance? Hyperthyroidism reduced stunning and improved muscle economy of the postischaemic rat heart. The activities of the mitochondrial sodium-calcium exchanger and mitochondrial K(+) channel in hyperthyroid rat hearts were different from those in the euthyroid rat hearts. These findings contribute to the understanding of mitochondrial bioenergetics in pathology and support thyroid therapy in the stunning induced by ischaemia. Transient ischaemia and hyperthyroidism are cardiovascular risk factors. Nevertheless, 3,5,3'-triiodothyronine/thyroxine therapy has been used to revert myocardial stunning. We studied the influence of hyperthyroidism on the role played by mitochondria in myocardial stunning consequent to ischaemia-reperfusion. Rats were injected s.c. daily with 20 µg kg(-1) triiodothyronine for 15 days (HpT group). Isolated ventricles from either HpT or euthyroid (EuT) rats were perfused in a calorimeter, and left intraventricular pressure (in millimetres of mercury) and heat release (Ht; in milliwatts per gram) were measured. Stunning was evoked by 20 min of no-flow ischaemia and 45 min reperfusion. The HpT hearts developed higher postischaemic contractile recovery (PICR) and improved total muscle economy (P/Ht) with lower diastolic contracture (ΔLVEDP) than EuT hearts. Release of Ca(2+) from the sarcoplasmic reticulum during reperfusion with 10 mm caffeine in low-[Na(+) ] Krebs solution evoked a higher contracture in EuT than in HpT hearts. Blockade of the mitochondrial sodium-calcium exchanger with clonazepam increased ΔLVEDP and reduced P/Ht and PICR in HpT but not in EuT hearts. The clonazepam-induced dysfunction in HpT hearts was reduced by ciclosporin, suggesting a dependance on activation of the mitochondrial permeability transition pore. Blockade of the mitochondrial Ca(2+) uniporter with Ru360 reduced P/Ht and PICR to â¼10% in both HpT and EuT hearts. Blockade of mitochondrial K(+) channels with 5-hydroxydecanoate increased LVEDP and reduced PICR and P/Ht in HpT hearts, while it only increased LVEDP in EuT hearts. The results suggest that hyperthyroidism prevents the stunning with high dependence on the mitochondrial sodium-calcium exchanger and mitochondrial K(+) channels. Both HpT and EuT hearts showed a similar and critical role of the uniporter. The HpT hearts have a slow sarcoplasmic reticulum Ca(2+) loss and low mitochondrial Ca(2+) uptake.
Assuntos
Metabolismo Energético , Hiperparatireoidismo/metabolismo , Mitocôndrias Cardíacas/metabolismo , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Miocárdio Atordoado/prevenção & controle , Miócitos Cardíacos/metabolismo , Animais , Canais de Cálcio/efeitos dos fármacos , Canais de Cálcio/metabolismo , Sinalização do Cálcio , Modelos Animais de Doenças , Metabolismo Energético/efeitos dos fármacos , Feminino , Hiperparatireoidismo/induzido quimicamente , Hiperparatireoidismo/fisiopatologia , Preparação de Coração Isolado , Masculino , Moduladores de Transporte de Membrana/farmacologia , Mitocôndrias Cardíacas/efeitos dos fármacos , Proteínas de Transporte da Membrana Mitocondrial/antagonistas & inibidores , Proteínas de Transporte da Membrana Mitocondrial/metabolismo , Poro de Transição de Permeabilidade Mitocondrial , Contração Miocárdica , Traumatismo por Reperfusão Miocárdica/metabolismo , Traumatismo por Reperfusão Miocárdica/fisiopatologia , Miocárdio Atordoado/metabolismo , Miocárdio Atordoado/fisiopatologia , Miócitos Cardíacos/efeitos dos fármacos , Canais de Potássio/efeitos dos fármacos , Canais de Potássio/metabolismo , Ratos Wistar , Recuperação de Função Fisiológica , Retículo Sarcoplasmático/metabolismo , Trocador de Sódio e Cálcio/antagonistas & inibidores , Trocador de Sódio e Cálcio/metabolismo , Fatores de Tempo , Tri-Iodotironina , Função Ventricular Esquerda , Pressão VentricularRESUMO
Positron emission tomography with (18)F-fluorodeoxyglucose (FDG-PET) is considered the gold standard for myocardial viability. A pilot study was undertaken to compare FDG-PET using euglycemic hyperinsulinemic clamp before (18)F-fluorodeoxyglucose ((18)F-FDG) administration (PET-CLAMP) with a new proposed technique consisting of a 24-h low-carbohydrate diet before (18)F-FDG injection (PET-DIET), for the assessment of hypoperfused but viable myocardium (hibernating myocardium). Thirty patients with previous myocardial infarction were subjected to rest (99m)Tc-sestamibi-SPECT and two (18)F-FDG studies (PET-CLAMP and PET-DIET). Myocardial tracer uptake was visually scored using a 5-point scale in a 17-segment model. Hibernating myocardium was defined as normal or mildly reduced metabolism ((18)F-FDG uptake) in areas with reduced perfusion ((99m)Tc-sestamibi uptake) since (18)F-FDG uptake was higher than the degree of hypoperfusion-perfusion/metabolism mismatch indicating a larger flow defect. PET-DIET identified 79 segments and PET-CLAMP 71 as hibernating myocardium. Both methods agreed in 61 segments (agreement = 94.5 %, κ = 0.78). PET-DIET identified 230 segments and PET-CLAMP 238 as nonviable. None of the patients had hypoglycemia after DIET, while 20 % had it during CLAMP. PET-DIET compared with PET-CLAMP had a good correlation for the assessment of hibernating myocardium. To our knowledge, these data provide the first evidence of the possibility of myocardial viability assessment with this technique.
Assuntos
Dieta com Restrição de Carboidratos , Fluordesoxiglucose F18 , Técnica Clamp de Glucose , Imagem de Perfusão do Miocárdio/métodos , Miocárdio Atordoado/diagnóstico por imagem , Miocárdio/patologia , Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos , Adulto , Idoso , Circulação Coronária , Estudos de Viabilidade , Feminino , Fluordesoxiglucose F18/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Miocárdio Atordoado/metabolismo , Miocárdio Atordoado/fisiopatologia , Miocárdio/metabolismo , Projetos Piloto , Valor Preditivo dos Testes , Compostos Radiofarmacêuticos/metabolismo , Tecnécio Tc 99m Sestamibi , Sobrevivência de Tecidos , Tomografia Computadorizada de Emissão de Fóton ÚnicoRESUMO
Isolated rabbit hearts were exposed to ischemia (I; 15 min) and reperfusion (R; 5-30 min) in a model of stunned myocardium. I/R decreased left-ventricle O(2) consumption (46%) and malate-glutamate-supported mitochondrial state 3 respiration (32%). Activity of complex I was 28% lower after I/R. The pattern observed for the decline in complex I activity was also observed for the reduction in mitochondrial nitric oxide synthase (mtNOS) biochemical (28%) and functional (50%) activities, in accordance with the reported physical and functional interactions between complex I and mtNOS. Malate-glutamate-supported state 4 H(2)O(2) production was increased by 78% after I/R. Rabbit heart Mn-SOD concentration in the mitochondrial matrix (7.4±0.7 µM) was not modified by I/R. Mitochondrial phospholipid oxidation products were increased by 42%, whereas protein oxidation was only slightly increased. I/R produced a marked (70%) enhancement in tyrosine nitration of the mitochondrial proteins. Adenosine attenuated postischemic ventricular dysfunction and protected the heart from the declines in O(2) consumption and in complex I and mtNOS activities and from the enhancement of mitochondrial phospholipid oxidation. Rabbit myocardial stunning is associated with a condition of dysfunctional mitochondria named "complex I syndrome." The beneficial effect of adenosine could be attributed to a better regulation of intracellular cardiomyocyte Ca(2+) concentration.
Assuntos
Adenosina/administração & dosagem , Complexo I de Transporte de Elétrons/metabolismo , Mitocôndrias Cardíacas/metabolismo , Miocárdio Atordoado/metabolismo , Traumatismo por Reperfusão/metabolismo , Animais , Respiração Celular/efeitos dos fármacos , Modelos Animais de Doenças , Ventrículos do Coração/patologia , Peroxidação de Lipídeos , Mitocôndrias Cardíacas/efeitos dos fármacos , Mitocôndrias Cardíacas/patologia , Miocárdio Atordoado/tratamento farmacológico , Miocárdio Atordoado/patologia , Óxido Nítrico Sintase/metabolismo , Consumo de Oxigênio/efeitos dos fármacos , Coelhos , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/patologia , Superóxido Dismutase/metabolismoRESUMO
AIMS: Myocardial stunning is a contractile dysfunction that occurs after a brief ischaemic insult. Substantial evidence supports that this dysfunction is triggered by Ca2+ overload during reperfusion. The aim of the present manuscript is to define the origin of this Ca2+ increase in the intact heart. METHODS AND RESULTS: To address this issue, Langendorff-perfused mouse hearts positioned on a pulsed local field fluorescence microscope and loaded with fluorescent dyes Rhod-2, Mag-fluo-4, and Di-8-ANEPPS, to assess cytosolic Ca2+, sarcoplasmic reticulum (SR) Ca2+, and transmembrane action potentials (AP), respectively, in the epicardial layer of the hearts, were submitted to 12 min of global ischaemia followed by reperfusion. Ischaemia increased cytosolic Ca2+ in association with a decrease in intracellular Ca2+ transients and a depression of Ca2+ transient kinetics, i.e. the rise time and decay time constant of Ca2+ transients were significantly prolonged. Reperfusion produced a transient increase in cytosolic Ca2+ (Ca2+ bump), which was temporally associated with a decrease in SR-Ca2+ content, as a mirror-like image. Caffeine pulses (20 mM) confirmed that SR-Ca2+ content was greatly diminished at the onset of reflow. The SR-Ca2+ decrease was associated with a decrease in Ca2+ transient amplitude and a shortening of AP duration mainly due to a decrease in phase 2. CONCLUSION: To the best of our knowledge, this is the first study in which SR-Ca2+ transients are recorded in the intact heart, revealing a previously unknown participation of SR on cytosolic Ca2+ overload upon reperfusion in the intact beating heart. Additionally, the associated shortening of phase 2 of the AP may provide a clue to explain early reperfusion arrhythmias.
Assuntos
Cálcio/metabolismo , Contração Miocárdica/fisiologia , Traumatismo por Reperfusão Miocárdica/metabolismo , Miocárdio Atordoado/metabolismo , Retículo Sarcoplasmático/metabolismo , Potenciais de Ação/efeitos dos fármacos , Potenciais de Ação/fisiologia , Animais , Arritmias Cardíacas/metabolismo , Arritmias Cardíacas/fisiopatologia , Cafeína/farmacologia , Citosol/metabolismo , Diástole/fisiologia , Eletrocardiografia , Cinética , Masculino , Camundongos , Traumatismo por Reperfusão Miocárdica/fisiopatologia , Miocárdio Atordoado/fisiopatologia , Miocárdio/metabolismo , Perfusão , Inibidores de Fosfodiesterase/farmacologia , Pressão Ventricular/fisiologiaRESUMO
The aim of this study was to assess early preconditioning protection against stunning in conscious sheep and analyze the role of ATP-dependent potassium (KATP) channels in the protective mechanism. Chronically instrumented animals were submitted to a 12 min reversible ischemia and 2 h reperfusion. Early preconditioning, consisting of six 5 min occlusion-5 min reperfusion periods, followed by 45 min normoperfusion before the prolonged ischemia protected against stunning (P < 0.01). In these experimental conditions, current agents used to analyze sarcolemmal (sKATP) and mitochondrial (mKATP) KATP channels could not clearly establish their participation in the protective mechanism. At doses that inhibit sKATP channels they were unable to block preconditioning protection against stunning (glibenclamide) or conversely, blocked preconditioning at doses that do not inhibit these channels (HMR1098). Moreover, both mKATP channel agonists (diazoxide) and antagonists (5HD) protected against stunning, a response that could be due to their effect via an alternative mitochondrial pathway.
Assuntos
Precondicionamento Isquêmico Miocárdico , Canais KATP/metabolismo , Miocárdio Atordoado/metabolismo , Miocárdio Atordoado/prevenção & controle , Potenciais de Ação/fisiologia , Animais , Hemodinâmica , Masculino , Traumatismo por Reperfusão Miocárdica/fisiopatologia , Miocárdio Atordoado/fisiopatologia , Recuperação de Função Fisiológica , Ovinos , Fatores de TempoRESUMO
It used to be thought that the consequences of coronary artery disease were final, and that the prognosis of the patient was limited to the extent of the ventricular dysfunction. This paradigm changed radically when the concept of hibernating myocardium was introduced, which states the existence of tissue that can regain contractile function after being re-vascularized. This introduced a new concept in cardiology: myocardial viability. This work presents a clear example of the importance of detecting myocardial viability in selected patients, due to the impact not only in treatment but in prognosis as well. It is also emphasized that positron emission tomography (PET) is the gold standard method to detect myocardial viability.