RESUMO
Inadequate angiogenic response to ischemia in diabetic myocardium could result in poor collateral formation. Because hypoxia-inducible factor (HIF)-1alpha is a transcriptional activator of vascular endothelial growth factor (VEGF) and is critical for initiating angiogenic responses to hypoxia, we investigated the expression of HIF-1alpha and VEGF in specimens of human heart tissue to elucidate the molecular responses to myocardial ischemia in diabetic patients during unstable angina. Moreover, accumulation of a marker of protein nitration nitrotyrosine, as well as the superoxide anion (O(2)(-)) levels and inducible nitric oxide synthase (iNOS), were evaluated. Ventricular biopsy specimens from 15 type 2 diabetic and 14 nondiabetic patients presenting with unstable angina (ischemic group) and from 20 patients (11 type 2 diabetic and 9 nondiabetic patients) who underwent coronary bypass surgery without angina within the preceding 10 days (control group) were collected during coronary bypass surgery. Nondiabetic patients had higher HIF-1alpha and VEGF expressions compared with diabetic patients (P < 0.001). As compared with nondiabetic specimens, diabetic specimens showed higher levels of both iNOS mRNA and protein levels (P < 0.001) associated with the highest tissue levels of nitrotyrosine and O(2)(-) (P < 0.001). Diabetes is associated with increased myocardial tissue levels of iNOS, O(2)(-), and nitrotyrosine and reduced expression of myocardial angiogenesis factors during ischemia.
Assuntos
Angina Instável/fisiopatologia , Diabetes Mellitus Tipo 2/fisiopatologia , Fatores de Transcrição/genética , Tirosina/análogos & derivados , Fator A de Crescimento do Endotélio Vascular/genética , Doença Aguda , Angina Instável/complicações , Angina Instável/cirurgia , Circulação Colateral/fisiologia , Ponte de Artéria Coronária , Diabetes Mellitus Tipo 2/complicações , Feminino , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia , Masculino , Pessoa de Meia-Idade , Óxido Nítrico Sintase/genética , Óxido Nítrico Sintase Tipo II , RNA Mensageiro/análise , Superóxidos/metabolismo , Tirosina/metabolismo , Função VentricularRESUMO
We report an infrequent case of an adult patient with a coronary artery to pulmonary artery fistula associated with a coronary artery aneurysm, a critical stenosis of the left anterior descending coronary artery (LAD) and a LAD dissection located distally to the stenosis. The fistula was successfully closed with direct sutures by opening the aneurysm under complete cardiopulmonary bypass. The excess aneurysm wall was excised and aneurysmorrhaphy was performed. Closure of the distal opening of the fistula was carried out without pulmonary arteriotomy and the operation was completed with a coronary artery bypass graft on the LAD with the left internal mammary artery used as "free graft". Postoperative angiographic evaluation demonstrated a normal artery distribution and the patient was asymptomatic without recurrence at 6 months after the operation.