Endothelial nitric-oxide synthase (eNOS) is an important regulator of endothelial function and vascular tone in biological tissues. While endothelial dysfunction occurs following ischemia and has been attributed to altered NO ⅐ formation, the biochemical basis for this dysfunction is unknown. Therefore, studies were performed to determine the effects of myocardial ischemia and reperfusion on eNOS in isolated rat hearts subjected to periods of global ischemia or ischemia followed by reperfusion. eNOS activity was assayed by L-[ C]arginine to L-[14 C]citrulline conversion and alterations in the amount and distribution of eNOS determined by Western blotting and immunohistochemistry. While activity was preserved after 30 min of ischemia with a value of 1.1 ؎ 0.1 pmol ؋ min ؊1 ؋ mg of protein ؊1 , it decreased by 77% after 60 min and became nearly undetectable after 120 min. Reperfusion resulted in only a partial restoration of activity. The decline in activity with ischemia was due, in part, to a loss of eNOS protein. Hemodynamic studies showed that the onset of impaired vascular reactivity paralleled the loss of functional eNOS. Subjecting isolated eNOS to conditions of acidosis, which occur during ischemia, followed by restoration of pH as occurs on reperfusion, caused a combination of reversible and irreversible loss of activity similar to that seen in ischemic and reperfused hearts. Thus, loss of endothelial function following ischemia is paralleled by a loss of eNOS activity due to a combination of pH-dependent denaturation and proteolysis.Over the last decade it has been shown that the endothelium plays a critical role in the control of vascular tone (1). A labile vasodilating substance termed endothelium-derived relaxing factor was identified as nitric oxide (NO ⅐ ), 1 which is synthesized by a calcium dependent nitric-oxide synthase (NOS) in endothelial cells (2-4). Subsequently, it was observed that ischemia causes impaired endothelial reactivity (5). In the heart it was observed that coronary artery occlusion, as occurs in heart attack, results in endothelial dysfunction. In both isolated vascular ring and in vivo models, endothelium-dependent vasodilation is markedly decreased after myocardial ischemia and reperfusion (6 -8). Studies in humans have identified a similar decline in acetylcholine-induced vasodilation or even paradoxical vasoconstriction in areas adjacent to atherosclerotic plaques present in coronary arteries (9). Likewise, a diffuse vasomotor impairment in hypercholesterolemic and diabetic patients was seen showing that vascular dysfunction might occur in different pathological conditions (10, 11).Because of the major pathophysiological significance of impaired endothelial reactivity following ischemia, there has been great interest in determining its underlying mechanisms. Earlier studies verified that while receptor mediated endothelialdependent responses to acetylcholine as well as receptor-independent responses to calcium ionophore A23187 were lost, endothelium-independent agents such a...

clinicaltrials.gov Identifier: NCT01448642.

No abstract

Classe I: evidência ou concordância geral de que o tratamento é benéfico, útil e eficaz.Classe II: evidência conflitante e/ou divergência de opinião quanto à utilidade e à eficácia do tratamento.Classe IIa: forças das evidências/opiniões em favor da utilidade e da eficácia.Classe IIb: forças das evidências/opiniões menos bem estabelecidas quanto à utilidade e à eficácia.Classe III: evidência ou concordância geral de que o tratamento não é útil/eficaz e em alguns casos pode ser prejudicial. Nível de evidência A: presença de múltiplos estudos clínicos randomizados.Nível de evidência B: presença de um único estudo clínico randomizado ou de estudos não-randomizados.Nível de evidência C: consenso de especialistas.O nível de evidência será apresentado apenas para os tratamentos do infarto do miocárdio, não se aplicando aos procedimentos diagnósticos. Todos os métodos complementares deverão ser realizados por profissionais experientes, segundo as recomendações específicas de cada especialidade.

Cardiogenic shock, age, and ICH were important independent correlates of 30-day and 1-year mortality in STEMI patients receiving fibrinolytic therapy. In-hospital non-ICH major and minor bleeding were not independently associated with increased mortality at 30 days or 1 year.