THE INHIBITORY EFFECT OF REMOTE ISCHAEMIC CONDITIONING ON A CELLULAR MODEL OF CARDIAC HYPERTROPHY

Remote ischaemic conditioning (RIC) protects against ischaemia-reperfusion injury, but it is unclear whether it could also attenuate adverse cardiac remodelling post-MI. We hypothesised that RIC generates a blood born signal capable of reducing the hypertrophic response by modulating gene expression associated with remodelling. Superfusate was collected from ischaemic conditioned Langendorff perfused rat hearts (RIC-superfusate). Blood was taken from healthy volunteers after three cycles of upper arm conditioning (RIC-serum). The RIC-superfusate/serum was applied to H9c2 cardiomyoblasts in culture treated with endothelin-1 (ET-1) to stimulate hypertrophy. Immunofluorescence was used to determine cell area. Expression of four genes associated with cardiac remodelling: BNP, α-actin, βMHC and ms −1 were determined using qRT-PCR. Response was compared to saline/unconditioned serum. ET-1 (100 ng/ml) caused a significant degree of cellular hypertrophy after 48 h: 22.8±1.1 vs 16.4±0.7 mm 2 in untreated cells (n=300 p 2 and 23.6±1.5 to 16.1±1.1mm 2 respectively (n=300 p −1 (31.6±2.7 to 13.0±1.4, n=4 p −1 (15.4±2.7 to 7.0±0.7, n=4 p Our data supports the hypothesis that RIC initiated humoral signalling may attenuate the deleterious process of cardiac remodelling. The findings identify a new therapeutic approach that may be beneficial in reducing adverse ventricular hypertrophy post-MI.