Introduction Chronic obstructive pulmonary disease (COPD) is the 3 rd leading cause of death worldwide (Qureshi, Sharafkhaneh and Hanania 2014). COPD is a progressive condition with irreversible airway damage, and includes conditions such as emphysema and chronic bronchitis (Daheshia 2005). Patients are often at a greater risk of cardiovascular complications such as ischaemic heart disease, due to lifestyle associated risk factors, such as smoking. COPD patients are prescribed bronchodilators to improve lung function. Often, a combination of pharmacological therapies are prescribed, including β 2 adrenoceptor agonists and muscarinic receptor antagonists to alleviate bronchoconstriction. Recent clinical studies have associated the use of muscarinic receptor antagonists such as the short acting, ipratropium bromide and the long acting, tiotropium bromide with an increased risk of adverse cardiovascular effects, including myocardial infarction and stroke in COPD patients (Singh, Loke and Furberg 2008; Hilleman et al. 2009). Previous studies from our group have shown that ipratropium exacerbates myocardial injury in pre-clinical models of ischaemia/reperfusion injury (Harvey, Hussain and Maddock 2014). These clinical findings have prompted the urgent need to assess the cardiac safety profile of long acting muscarinic receptor antagonists (LAMAs), in experimental models of myocardial ischaemia/reperfusion injury. Aim To characterise the cardiac safety profiles of LAMAs in in-vitro models of myocardial ischaemia/reperfusion injury. Methods Briefly: Isolated perfused hearts were subjected to 35 min of regional ischaemia followed by reperfusion for 120 minutes (figure 1). For the drug treated groups; either Glycopyrronium, Aclidinium, Tiotropium or Umeclidinium (10μM-1nM) was administered throughout the reperfusion period. At the end of the experiment, hearts were subjected to TTC staining for infarct-to-risk ratio (%) analysis. Hearts that underwent ischaemia were also stained with Evans blue. Figure 1: The experimental protocols used for the Langendorff models. KH – Krebs- Henseleit buffer. Cardiac Safety Profiles of Long Acting Muscarinic Receptor Antagonists Used in the Treatment of Chronic Obstructive Pulmonary Disease Shabana Cassambai, Sadie Dean, Christopher J Mee, Afthab Hussain Faculty Research Centre - Applied Biological and Exercise Sciences, Coventry University, CV1 5FB Conclusion This is the first pre-clinical study to suggest that the administration of LAMAs during reperfusion, exacerbates myocardial ischaemia/reperfusion injury in an in-vitro isolated heart model. In order to determine the signalling mechanisms underlying this exacerbated myocardial injury; further studies examining the activation of cell death pathways and molecular changes associated with drug administration are urgently required. Results Figure 2: Glycopyrronium Bromide (10μM-1nM) administration does not significantly increase Infarct size to risk ratio. Mean ± SEM n=4, ****P<0.0001 vs. normoxia. Figure 3 : Aclidinium Bromide administration significantly increases infarct development at concentrations of 10μM, 10nM and 1nM. Mean ± SEM n=3, **** P<0.0001 vs. normoxia, ### P<0.001 vs. IR, ## P<0.01 vs. IR, $ P<0.05 vs. IR+AB (10μM), € P<0.05 vs. IR+AB (1μM), ^^ P<0.01 vs. IR+AB (100nM). Figure 4: Tiotropium Bromide administration during reperfusion results in a significant increase in infarct development at all concentrations. Mean ± SEM n=3, **** P<0.0001 vs. normoxia, #### P<0.0001 vs. IR, ### P<0.001 vs. IR, ## P<0.01 vs. IR. Figure 5: Administration of Umeclidinium Bromide (100nM, 10nM and 1nM) throughout reperfusion increases infarct size to risk ratio (%). Mean ± SEM n=4, **** P<0.0001 vs. normoxia, #### P<0.0001 vs. IR, €€€€ P<0.0001 vs. IR+UB (1μM). References Daheshia, M. (2005) 'Pathogenesis of Chronic Obstructive Pulmonary Disease (COPD)'. Clinical and Applied Immunology Reviews 5 (5), 339-351 Harvey, K. L., Hussain, A., and Maddock, H. L. (2014) 'Ipratropium Bromide-Mediated Myocardial Injury in in Vitro Models of Myocardial ischaemia/reperfusion'. Toxicological Sciences : An Official Journal of the Society of Toxicology 138 (2), 457-467 Hilleman, D. E., Malesker, M. A., Morrow, L. E., and Schuller, D. (2009) 'A Systematic Review of the Cardiovascular Risk of Inhaled Anticholinergics in Patients with COPD'. International Journal of Chronic Obstructive Pulmonary Disease 4, 253-263 Qureshi, H., Sharafkhaneh, A., and Hanania, N. A. (2014) 'Chronic Obstructive Pulmonary Disease Exacerbations: Latest Evidence and Clinical Implications'. Therapeutic Advances in Chronic Disease, 2040622314532862 Singh, S., Loke, Y. K., and Furberg, C. D. (2008) 'Inhaled Anticholinergics and Risk of Major Adverse Cardiovascular Events in Patients with Chronic Obstructive Pulmonary Disease: A Systematic Review and Meta-Analysis'. JAMA - Journal of the American Medical Association 300 (12), 1439-1450