Immunocytochemical evidence for inducible nitric oxide synthase and cyclooxygenase-2 expression with nitrotyrosine formation in human hibernating myocardium

Myocardial hibernation may result from repetitive episodes of transient ischaemia leading to prolonged dysfunction. Inducible nitric oxide synthase (iNOS) expression has been demonstrated in animals following brief, non-lethal ischaemia-reperfusion injury. We therefore, hypothesised that in human hi...

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Bibliographic Details
Published in:Basic research in cardiology 2002-09, Vol.97 (5), p.409-415
Main Authors: Baker, Christopher S R, Dutka, David P, Pagano, Domenico, Rimoldi, Ornella, Pitt, Michael, Hall, Roger J C, Polak, Julia M, Bonser, Robert S, Camici, Paolo G
Format: Article
Language:English
Subjects:
Angiotensin-Converting Enzyme Inhibitors - therapeutic use
Biopsy
Coronary Disease - enzymology
Coronary Disease - metabolism
Coronary Disease - pathology
Cyclooxygenase 2
Diuretics - therapeutic use
Echocardiography
Humans
Immunohistochemistry - methods
Isoenzymes - metabolism
Membrane Proteins
Middle Aged
Myocardial Stunning - enzymology
Myocardial Stunning - metabolism
Myocardial Stunning - pathology
Myocardium - enzymology
Myocardium - pathology
Nitric Oxide Synthase - metabolism
Nitric Oxide Synthase Type II
Prostaglandin-Endoperoxide Synthases - metabolism
Tyrosine - analogs & derivatives
Tyrosine - analysis
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Summary:Myocardial hibernation may result from repetitive episodes of transient ischaemia leading to prolonged dysfunction. Inducible nitric oxide synthase (iNOS) expression has been demonstrated in animals following brief, non-lethal ischaemia-reperfusion injury. We therefore, hypothesised that in human hibernating myocardium: 1). iNOS would be present; 2). the reaction of nitric oxide and superoxide would form the strong oxidant peroxynitrite; 3) that this process would be accompanied by the expression of cyclooxygenase-2 (Cox-2) which interacts with NOS and whose products could further affect myocardial function. In sixteen patients with coronary artery disease (CAD), left ventricular biopsies were obtained from chronically dysfunctional segments subtended by a stenotic artery (> 75 %) and shown to be viable by (18)F-fluorodeoxyglucose positron emission tomography. Comparison was made with myocardial biopsies (n = 8) from normally contracting myocardium in patients undergoing coronary surgery, from unused transplant donors and at post-mortem. Regional wall motion score improved in all patients 6 months post-revascularisation (from 2.7 +/- 0.7 to 1.5 +/- 0.5; p < 0.001), confirming hibernation. Immunocytochemistry localized reactivity to iNOS, Cox-2 and nitrotyrosine (a marker of peroxynitrite formation) to cardiomyocytes from hibernating segments. No difference in reactivity to endothelial NOS was seen between hibernating and control cardiomyocytes. Cox-2 and iNOS are co-expressed in hibernating myocardium with nitrotyrosine suggesting nitric oxide production and peroxynitrite formation. We propose that this is secondary to ischaemia-reperfusion and that the products of these enzymes may have consequences for myocardial contractile function and survival.
ISSN:0300-8428
1435-1803
DOI:10.1007/s003950200050