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04 The bronchodilator salbutamol is associated with increased myocardial injury in a pre-clinical heart attack model
  1. A Nagra,
  2. H Maddock,
  3. A Hussain
  1. Bio-molecular Sciences Applied Research Group, Faculty of Health and Life Sciences, Coventry University, UK

Abstract

Salbutamol is widely used to treat symptoms of chest tightness commonly associated with Asthma. Recent studies have associated increased in morbidity and mortality in asthmatic patients with underlying heart disease currently being treated with salbutamol. The study aimed to investigate the effects of salbutamol on the myocardium subjected to ischaemia-reperfusion (I/R). Langendorff hearts were subjected to control or I/R in the absence or presence of salbutamol (1–100 nM)±CGP-12177 (β1 adrenoceptor antagonist) or ICI 118551 (β2 adrenoceptor antagonist). Hearts underwent triphenyl tetrazolium staining for infarct size assessment. Isolated cardiomyocytes were exposed to simulated I/R in the absence or presence of salbutamol (1 pM–1 μM)±CGP-12177 or ICI 118551. Cellular injury was determined by measurement of viability, apoptosis and necrosis using flow cytometry. Hypercontracture was also assessed in cardiomyocytes subjected to oxidative stress in the absence or presence of salbutamol. Salbutamol (100 nM) significantly increased infarct size to risk ratio (%) compared to controls (76±3% vs 51±2%, p<0.001, respectively). Administration of salbutamol in the presence of the CGP-12177 or ICI 118551 completely reversed the cardio-toxic effects of salbutamol (63±4%, p<0.01, 50±2%, p<0.001, respectively). Salbutamol significantly increased apoptosis/necrosis compared to non-treated cardiomyocytes subjected to hypoxia/reoxygenation, the cardio-toxic effect of salbutamol abrogated by CGP-12177 and ICI 118551. Salbutamol also reduced hypercontracture time in cardiomyocytes subjected to oxidative stress. This study is the first to identify the cardiotoxic effects of salbutamol in a pre-clinical heart attack model. Further studies are being investigated to determine the mechanism of action of the myocardial injury associated with salbutamol.

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