کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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5828431 | 1558963 | 2013 | 9 صفحه PDF | دانلود رایگان |
Excessive levels of catecholamines are believed to contribute to cardiac dysfunction in a variety of disease states, including myocardial infarction and heart failure, and are particularly implicated in stress-induced cardiomyopathy, an increasingly recognized cardiomyopathy associated with significant morbidity and mortality. We have previously shown that a high dose of isoprenaline induces reversible regional dysfunction of the left ventricle in mice. We now hypothesize that adenosine can prevent cardiac dysfunction in this mouse model of stress-induced cardiomyopathy. Hundred male C57BL/6 mice were injected with 400Â mg/kg isoprenaline and then randomized to either 400Â mg/kg adenosine or saline. Cardiac function was evaluated by echocardiography at baseline and 2, 24, 48, 72, 96 and 120Â min post isoprenaline. Myocardial fibrosis was quantified after 10 days. Intracellular lipid accumulation was quantified after 2 and 24Â h. Electrophysiological parameters and degree of lipid accumulation were evaluated in cultured HL1 cardiomyocytes. Two hours post isoprenaline treatment, echocardiographic parameters of global and posterior wall regional function were significantly better in adenosine-treated mice (P<0.05). This difference persisted at 24Â h, but saline-treated mice gradually recovered over the next 96Â h. Intracellular lipid accumulation was also significantly lower in adenosine mice. We found no sign of fibrosis in the adenosine mice, whereas the extent of fibrosis in isoprenaline mice was 1.3% (P<0.05). Furthermore, adenosine-treated HL1 cells showed preserved electrophysiological function and displayed less severe intracellular lipid accumulation in response to isoprenaline. In conclusion, adenosine attenuates isoprenaline-induced cardiac dysfunction in mice and cells.
Journal: European Journal of Pharmacology - Volume 718, Issues 1â3, 15 October 2013, Pages 475-483