Production of oxidative products of nitric oxide in infarcted human heart

Objectives. We sought to assess whether oxidation products of nitric oxide (NO), nitrite (NO2−) and nitrate (NO3−), referred to as NOx, are released by the heart of patients after acute myocardial infarction (AMI) and whether NOxcan be determined in peripheral blood of these patients. Background. Previously we reported that in experimental myocardial infarction (rabbits) NOxis released mainly by inflammatory cells (macrophages) in the myocardium 3 days after onset of ischemia. NOxis formed in heart muscle from NO; NO originates through the activity of the inducible form of nitric oxide synthase (iNOS). Methods. Eight patients with acute anterior MI and an equal number of controls were studied. Coronary venous blood was obtained by coronary sinus catheterization; NOxconcentrations in coronary sinus, in arterial and peripheral venous plasma were measured. Left ventricular end-diastolic pressure was determined. Measurements were carried out 24, 48 and 72 h after onset of symptoms. The type and location of coronary arterial lesions were determined by coronary angiography. Plasma NO3−was reduced to NO2−by nitrate reductase before determination of NO2−concentration by chemiluminescence. Results. The results provided evidence that in patients with acute anterior MI, the myocardial production of nitrite and nitrate (NOx) was increased, as well as the coronary arterial–venous difference. Increased NOxproduction by the infarcted heart accounted for the increase of NOxconcentration in arterial and the peripheral venous plasma. The peak elevation of NOxoccurred on days 2 and 3 after onset of the symptoms, suggesting that NOxproduction was at least in part the result of production of NO by inflammatory cells (macrophages) in the heart. Conclusions. The appearance of oxidative products of NO (NO2−and NO3−) in peripheral blood of patients with acute MI is the result of their increased release from infarcted heart during the inflammatory phase of myocardial ischemia. Further studies are needed to define the clinical value of these observations.