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| 126P London, UK Pharmacology 2016 |
The effect of aging on ischaemia-reperfusion injury and cardioprotection
Introduction: Aging is characterised by decline in metabolic and physiological functions (1), potentially leading to cardiovascular disorders (2). Although a myriad of novel cardioprotective strategies have been discovered, their translation to the clinical setting has been disappointing (3). This has been attributed to factors including inadequate models of ischaemia-reperfusion injury used in preclinical cardioprotection studies. This pre-clinical study was designed to investigate the effect of aging on cardioprotective strategies in ischaemia-reperfusion injury in young and middle aged rats.
Method: Male Sprague-Dawley rats were separated into 3 and 6 months (3M and 6M, respectively) age groups: control, Ischaemia Pre-Conditioning (IPC), Simvastatin (10µM), Cyclosporine-A (CsA) (200nM), all drugs were dissolved in DMSO. Isolated rat hearts were subjected to 40 minutes stabilisation; 20 minutes global-ischaemia and 120 minutes reperfusion. IPC groups were subjected to 3 cycles of 10 minute reperfusion and 2 cycles of 5 minutes ischaemia prior to 20 minutes global-ischaemia followed with 120 minutes of reperfusion. In the drug groups, treatments occurred at the onset of reperfusion for 15 minutes. Following the experiments, tetratozolium chloride was used to distinguish between viable tissue and non-viable tissue. Data is expressed as mean±SEM (4-5 animals). One-Way ANOVA was used for analysis with Dunnett’s Multiple Comparison test followed by Mann-Whitney test.
Results: In the 3M and 6M control groups no statistical significance was observed in infarct sizes (49.20± 2.34 vs 48.78± 4.14%, respectively). In the 3M groups; IPC, Simvastatin and CsA showed significant reduction in infarct size when compared with Control (29.74± 3.69, 32.76± 3.48, 17.51± 1.738 vs. 49.20± 2.34%, respectively, P<0.01). At 6M, Simvastatin and CsA showed significant infarct reduction with respect to Control (30.68± 1.22 and 33.72± 3.24 vs. 48.78± 4.14%, respectively, P<0.05). Infarct sizes showed significant reduction from 6M to 3M for IPC (42.14± 3.93% vs 29.74± 3.70%, respectively, P<0.05) and CsA (33.72± 3.24% vs. 17.51± 1.74%, respectively, P<0.005). In the Simvastatin treated 3M and 6M treatment groups no statistical significance was observed (32.76± 3.48 vs. 30.68± 1.22%, respectively).
Conclusion: This study indicates that aging attenuates the cardioprotective effects of IPC and CsA in aged groups. Further studies are required to elucidate the mechanisms involved in aged-related attenuation of cardioprotective strategies.
References:
(1) Capitanio, D. et al. (2016) EuPA Open Proteomics [online] 12, 22-30.
(2) Ali Raza, J. and Movahed, A. (2002). International Journal of Cardiology 85 (2-3), 203-215.
(3) Hausenloy et al (2010) Basic Res Cardiol. Nov; 105(6): 677-686