RESUMO
The objective of the present research was to study transformations of various physiological NO forms in an isolated rat heart, perfused with the medium, containing dinitrosyl iron complexes with glutathione ligand (DNIC-GH). We showed that such aerobic perfusion resulted in accumulation of mostly diamagnetic NO physiological forms (S-nitrosothiols) in myocardial tissue. They were transformed into protein-bound mononuclear dinitrosyl iron complexes during subsequent total ischemia. Meantime, DNIC-GH injection on the onset of ischemia resulted in the changes in the state of mitochondrial respiratory state, characterized by the increase in myocardial concentration of flavosemiquinones.
Assuntos
Ferro/química , Miocárdio/química , Óxido Nítrico/química , Óxidos de Nitrogênio/química , S-Nitrosotióis/química , Animais , Espectroscopia de Ressonância de Spin Eletrônica , Glutationa/química , Coração/efeitos dos fármacos , Ferro/farmacologia , Isquemia , Ligantes , Mitocôndrias Cardíacas/química , Mitocôndrias Cardíacas/efeitos dos fármacos , Óxidos de Nitrogênio/farmacologia , Técnicas de Cultura de Órgãos , Perfusão , Quinonas/química , RatosRESUMO
The injection of dinitrosyliron iron complexes with glutathione at the onset of 40-min rat regional myocardial ischemia was shown to exert a clear cardioprotective action by decreasing the infarct size and suppressing the cardiac rhythm disturbance. After the introduction of the preparation, its effective accumulation with protein thiol-containing ligands in the myocardial tissue was registered be the EPR method. It was also found that, as a result of postischemic reperfusion, the rate of the decrease in the content of these complexes in the ischemic area increases, which demonstrates the effective scavenging of short-lived reactive oxygen species by molecules of dinitrosyl iron complexes.
Assuntos
Arritmias Cardíacas/prevenção & controle , Circulação Cerebrovascular , Glutationa/uso terapêutico , Ferro/uso terapêutico , Infarto do Miocárdio/prevenção & controle , Isquemia Miocárdica/tratamento farmacológico , Miocárdio/metabolismo , Óxidos de Nitrogênio/uso terapêutico , Vasodilatadores/uso terapêutico , Animais , Arritmias Cardíacas/fisiopatologia , Glutationa/química , Glutationa/metabolismo , Ferro/química , Ferro/metabolismo , Masculino , Infarto do Miocárdio/patologia , Isquemia Miocárdica/patologia , Isquemia Miocárdica/fisiopatologia , Reperfusão Miocárdica , Óxidos de Nitrogênio/química , Óxidos de Nitrogênio/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Wistar , Distribuição Tecidual , Vasodilatadores/metabolismoRESUMO
Changes in nitric oxide concentration in rat myocardium in vivo during temporary occlusion of the anterior descending coronary artery, followed by reperfusion were studied by microdialysis assay in risk and intact areas by using an NO spin trap (complex of ferrous ions with N-methyl-D, L-glucamine dihiocarbamate, Fe3+-MGD2). The amplitude of the EPR signal of the NO spin adduct NO-Fe2+-MGD2 in the risk area increased during the 40-min occlusion and remained higher than the initial level during 60-min postischemic reperfusion, indicating a substantial nitric oxide production. The size of the infarction in the risk area by the end of reperfusion was 47 +/- 3 %, the contents of ATP, phosphocreatine, and total creatine decreased to 44 +/- 4, 51 +/- 5, and 60 +/- 3 %, correspondingly, as compared with initial values, and the level of lactate was six times higher than the initial one. In the intact area of the left ventricle, the level of nitric oxide and high-energy metabolites did not change throughout the experiment. It was shown that the intensive nitric oxide production, in acute regional ischemia and reperfusion are related to the disturbance of energy metabolism, the damage to cytoplasmic membranes, and the death of cardiomyocytes.