33 Investigation into the effects of administering β-adrenoceptor agonists during myocardial ischaemia-reperfusion

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Abstract

β-Adrenoceptors agonists such as Salbutamol and Salmeterol are bronchodilators used to alleviate the symptoms of asthma. Recent clinical studies have associated certain bronchodilators with an increase in morbidity and mortality in asthmatic patients with underlying heart disease.1 This study investigated the effects of Salbutamol and Salmeterol on the myocardium subjected to ischaemia-reperfusion (I/R) in Langendorff heart model and adult cardiomyocytes. Perfused hearts were subjected to 35 min ischaemia and 120 min reperfusion. Hearts underwent triphenyl tetrazolium staining for infarct size measurement. Isolated adult cardiomyocytes were loaded with a fluorophore and subjected to laser induced oxidative stress. The onset of depolarisation and hypercontracture were recorded. Treatment groups (n=6) were subjected to control or I/R ± Salbutamol (100 nM) ± CGP-12177 (1.4 nM) (β1 adrenoceptor antagonist) or ICI 118551 (1.2 nM) (β 2 adrenoceptor antagonist). All experiments were repeated in the presence of Salmeterol. In the Langendorff model, Salbutamol (1 nM–1 μM) but not Salmeterol (100 nM–1 μM) significantly increased infarct size to RR (%) vs controls (100 nM Salbutamol; 76±3% vs 51±2%, p<0.001). Salbutamol in the presence of CGP-20712 or ICI 118551 significantly abrogated the cardiotoxic effects of Salbutamol (63±4%, p<0.01, 50±2%, p<0.001). In a cardiomyocyte oxidative stress model, Salbutamol (100 nM) significantly reduced the time taken to depolarisation and hypercontracture (p<0.05) compared to the control (223±4 vs 251±7 and 438±61 vs 630±13, respectively). This is the first study to identify and differentiate the effect of short acting and long acting β adrenoceptors agonists under conditions of myocardial IR.

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