title: Adenosine prevents isoprenaline-induced cardiac contractile and electrophysiological dysfunction.
abstract: 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 400mg/kg isoprenaline and then randomized to either 400mg/kg adenosine or saline. Cardiac function was evaluated by echocardiography at baseline and 2, 24, 48, 72, 96 and 120 min post isoprenaline. Myocardial fibrosis was quantified after 10 days. Intracellular lipid accumulation was quantified after 2 and 24h. 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 24h, but saline-treated mice gradually recovered over the next 96 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.
authors: Department of Molecular and Clinical Medicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
authors: Yangzhen
authors: Y
authors: Shao
authors: Björn
authors: B
authors: Redfors
authors: Lillemor
authors: L
authors: Mattson-Hultén
authors: Margareta
authors: M
authors: Scharing Täng
authors: Elma
authors: E
authors: Daryoni
authors: Mohammed
authors: M
authors: Said
authors: Elmir
authors: E
authors: Omerovic
mesh_terms: D000241:Adenosine / Q000494:pharmacology*; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D055724:Electrophysiological Phenomena / Q000187:drug effects*; D005355:Fibrosis; D006321:Heart / Q000187:drug effects* / Q000502:physiology*; D007545:Isoproterenol / Q000633:toxicity*; D008055:Lipids / Q000097:blood; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009119:Muscle Contraction / Q000187:drug effects*; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects; D059467:Transcriptome / Q000187:drug effects
chemical_list: D015415:Biomarkers; D008055:Lipids; D000241:Adenosine; D007545:Isoproterenol
keywords: Adenosine; Cardiac dysfunction; Isoprenaline; Mouse; Stress-induced cardiomyopathy