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Semi-Minimal Invasive Method to Induce Myocardial Infarction in Rats and the Assessment of Cardiac Function by an Isolated Working Heart System
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N-Acetylcysteine Ameliorates Experimental Autoimmune Myocarditis in Rats via Nitric Oxide
Kana Shimada1, Hiroyasu Uzui2, Takanori Ueda2
1Department of Cardiovascular Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Journal of Cardiovascular Pharmacology and Therapeutics
|August 23, 2014
Summary
N-acetylcysteine (NAC) treatment reduced oxidative stress and improved cardiac pathology in rats with experimental autoimmune myocarditis. The therapeutic effects were mediated through the nitric oxide (NO) system.
Area of Science:
- Cardiovascular Research
- Immunology
- Oxidative Stress
Background:
- Oxidative stress is implicated in the pathogenesis of myocarditis.
- Experimental autoimmune myocarditis (EAM) serves as a model to study inflammatory heart disease.
Purpose of the Study:
- To investigate the therapeutic effects of N-acetylcysteine (NAC), an antioxidant, on EAM in a rat model.
- To elucidate the role of the nitric oxide (NO) system in NAC's protective effects against myocarditis.
Main Methods:
- EAM was induced in rats using porcine myosin.
- Rats received daily intraperitoneal injections of NAC (20 mg/kg/d) or saline from day 1 to 21.
- Additional groups were treated with NAC combined with N(G)-nitro-l-arginine methylester (l-NAME) or its inactive enantiomer, d-NAME, to assess the involvement of nitric oxide synthase (NOS).
Main Results:
- NAC treatment significantly improved cardiac pathology and reduced superoxide production in EAM rats.
- The beneficial effects of NAC were diminished when co-administered with l-NAME, but not d-NAME, indicating a role for the NO system.
- NAC reduced intercellular adhesion molecule 1 expression, increased myocardial c-kit(+) cells, and tended to reduce inflammation-induced left ventricular mass.
Conclusions:
- N-acetylcysteine (NAC) ameliorates myocardial injury in a rat model of experimental autoimmune myocarditis.
- The protective mechanisms of NAC involve the nitric oxide (NO) system.
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