Production of oxidative products of nitric oxide in infarcted human heart.
OBJECTIVE
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 NOx can be determined in peripheral blood of these patients.


BACKGROUND
Previously we reported that in experimental myocardial infarction (rabbits) NOx is released mainly by inflammatory cells (macrophages) in the myocardium 3 days after onset of ischemia. NOx is 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; NOx concentrations 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 NOx production by the infarcted heart accounted for the increase of NOx concentration in arterial and the peripheral venous plasma. The peak elevation of NOx occurred on days 2 and 3 after onset of the symptoms, suggesting that NOx production 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.
Akiyama
K
K
Department of Experimental Cardiology, Huntington Medical Research Institutes, Pasadena, California 91101, USA.
Kimura
A
A
Suzuki
H
H
Takeyama
Y
Y
Gluckman
T L
TL
Terhakopian
A
A
Katagiri
T
T
Suh
K Y
KY
Roseto
J
J
Bing
R J
RJ
D000368:Aged; D000369:Aged, 80 and over; D001158:Arteries; D017023:Coronary Angiography; D003331:Coronary Vessels; D003971:Diastole; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008163:Luminescent Measurements; D008264:Macrophages / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood / Q000378:metabolism*; D017202:Myocardial Ischemia / Q000378:metabolism / Q000473:pathology; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D050901:Nitrate Reductase; D009565:Nitrate Reductases / Q000378:metabolism; D009566:Nitrates / Q000378:metabolism; D009569:Nitric Oxide / Q000097:blood / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D009573:Nitrites / Q000378:metabolism; D010084:Oxidation-Reduction; D014680:Veins; D016277:Ventricular Function, Left; D017725:Ventricular Pressure
D009566:Nitrates; D009573:Nitrites; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D009565:Nitrate Reductases; D050901:Nitrate Reductase