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25 Acetylcholine protects against ipratropium induced myocardial injury
  1. K L Simmons,
  2. A Hussain,
  3. H L Maddock
  1. Biomolecular Sciences Applied Research Group, Faculty of Health and Life Sciences, Coventry University, Coventry, UK

Abstract

Concerns have been raised regarding the cardiovascular safety of muscarinic receptor antagonists, such as Ipratropium bromide for use in asthmatic patients with underlying heart disease.1 2 The aims of this study were to determine the involvement of Ipratropium at the muscarinic receptor on myocardial ischaemia/reperfusion injury in isolated adult cardiomyocyte cell death and oxidative stress models. The MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay revealed that in isolated cardiomyocytes, under conditions of hypoxia/reoxygenation, Ipratropium (0.1 picoM–10 μM) inhibits cell viability, in a dose responsive manner. Addition of acetylcholine (0.1 μM) was shown to significantly increase cell viability compared with untreated controls (114.05%±4.35 vs 100% Control). The addition of Ipratropium (0.1 μM) in the presence of acetylcholine (0.1 μM) was shown to abrogate the damage observed in the Ipratropium treated group (94.56%±3.65 vs 97.84%±2.47). In a cardiomyocyte model of oxidative stress, mitochondrial depolarisation (Dep) and Hypercontracture (Hyp) (rigour) were recorded via use of confocal microscopy. Adult cardiac myocytes were subjected to oxidative stress in the presence and absence of Ipratropium (0.01, 0.1 and 1 μM) and acetylcholine (0.1 μM). Ipratropium significantly reduced the time taken for Dep and Hyp of the cardiac myocytes (Abstract 25 table 1, n=5). Adminstration of Ipratropium in conjunction with acetylcholine significantly reversed the induced myocardial injury. The exacerbation of myocardial injury by Ipratropium involves disturbance of the mitochondria. This may involve the inhibition of protective muscarinic signalling pathways.

Abstract 25 Table 1

Effect of Ipratropium and acetylcholine on depolarisation and hypercontracture of adult cardiomyocytes

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