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Inflammatory cell-derived NO modulates cardiac allograft contractile and electrophysiological function
N K Worrall1, R T Pyo, M D Botney
1Department of Surgery, Washington University School of Medicine, St. Louis 63110, USA.
The American Journal of Physiology
|July 1, 1997
Summary
Inhibition of inducible nitric oxide synthase (iNOS) in inflammatory cells prevents early cardiac allograft dysfunction. This finding suggests iNOS inhibition as a potential therapy for immune-mediated myocardial issues.
Area of Science:
- Cardiology
- Immunology
- Transplantation
Background:
- Acute cardiac allograft rejection impairs heart function.
- Inducible nitric oxide synthase (iNOS) plays a role in this rejection process.
Purpose of the Study:
- To characterize contractile and electrophysiological dysfunction in early acute cardiac allograft rejection.
- To examine the role of nitric oxide (NO) and iNOS in this dysfunction.
- To identify cells expressing iNOS during early rejection.
Main Methods:
- Utilized a rat cardiac transplant model.
- Assessed papillary muscle contractility and electrophysiology.
- Measured iNOS mRNA expression and enzyme activity.
- Administered corticosteroids and a direct iNOS inhibitor (aminoguanidine).
Main Results:
- Early allograft rejection caused significant contractile and electrophysiological deficits before myocyte necrosis.
- iNOS mRNA was found in infiltrating inflammatory cells, not in graft cells.
- Corticosteroids and aminoguanidine attenuated dysfunction and inhibited iNOS activity.
Conclusions:
- Early cardiac allograft dysfunction is largely mediated by iNOS in inflammatory cells.
- Corticosteroid efficacy may stem from iNOS inhibition.
- Targeting iNOS presents a potential therapeutic strategy for immune-mediated myocardial dysfunction.