RESUMO
BACKGROUND: Cardiac oxytocin (OT) is structurally identical to that found in the hypothalamus, indicating that this active form of OT is derived from the same gene. The abundance of OT and its receptors in atrial myocytes suggests that, directly and/or via the release of the cardiac hormone atrial natriuretic peptide, this hormone regulates the force of cardiac contractions. Previous studies have demonstrated a role of OT in myocardial inflammatory responses. We sought to study protective myocardial and anti-inflammatory effects of OT in the immediate post-transplant period. METHODS: We grouped adult male Albino rats into sham, control, and OT-treated groups. Control and treated groups underwent heterotopic cervical heart transplantation. Myocardial injury was assessed by measuring plasma cardiac troponin I, and myocardial proinflammatory cytokines as well as by performing histopathologic assessments injury score, and of apoptotic degree. Myocardial myeloperoxidase, neutrophil infiltration, neutrophil chemotactic mediators as well as formation of reactive oxygen and reactive nitrogen species were measured in the myocardium at 3 hours after reperfusion to assess neutrophil-dependent myocardial injury. RESULTS: OT downregulates neutrophil chemotactic molecules--KC/CXCL1 and MIP-2/CXCL2. The decrement in myocardial PMN infiltration was associated with reduced reactive oxygen and reactive nitrogen species formation in the myocardium at 3 hours after reperfusion following global ischemia. OT reduced postmyocardial ischemia/reperfusion apoptotic processed. CONCLUSION: OT ameliorated immediate myocardial injury in heart grafts, through downregulation of the inflammatory response, of reactive oxygen species, and of neutrophil dependent apoptosis.
Assuntos
Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Apoptose/efeitos dos fármacos , Transplante de Coração/efeitos adversos , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Miocárdio/patologia , Neutrófilos/efeitos dos fármacos , Ocitocina/farmacologia , Animais , Biomarcadores/sangue , Quimiotaxia de Leucócito/efeitos dos fármacos , Citocinas/metabolismo , Citoproteção , Modelos Animais de Doenças , Mediadores da Inflamação/metabolismo , Masculino , Traumatismo por Reperfusão Miocárdica/sangue , Traumatismo por Reperfusão Miocárdica/etiologia , Traumatismo por Reperfusão Miocárdica/imunologia , Traumatismo por Reperfusão Miocárdica/patologia , Miocárdio/imunologia , Miocárdio/metabolismo , Infiltração de Neutrófilos/efeitos dos fármacos , Neutrófilos/imunologia , Neutrófilos/metabolismo , Neutrófilos/patologia , Estresse Oxidativo/efeitos dos fármacos , Peroxidase/metabolismo , Ratos , Fatores de Tempo , Troponina I/sangueRESUMO
BACKGROUND: Mouse transplant models offer a valuable platform for studying the biology of a spectrum of diseases, particularly those of the immune system. We have developed a modified abdominal heterotopic heart transplantation (AHHT) model with a total arterial anastomosis and compared the results with the cervical heterotopic heart transplantation (CHHT) and the non-modified AHHT models. METHODS: Mice were randomly assigned to four groups: sham, AHHT, CHHT, and modified AHHT groups. Each group (except for the sham) included donor and recipient animals. Postoperative outcome, operative mortality, operative time, and tissue damage were assessed by measuring plasma levels of tumor necrosis factor α. RESULT: The modified AHHT group had significantly lower values. However, hind limb paralysis was observed equally and only in AHHT and modified AHHT models. The modified AHHT group had the highest success rate of functioning hearts.
