PT  - JOURNAL ARTICLE
AU  - A P Vanezis
AU  - S A Edroos
AU  - N J Samani
AU  - G C Rodrigo
TI  - THE INHIBITORY EFFECT OF REMOTE ISCHAEMIC CONDITIONING ON A CELLULAR MODEL OF CARDIAC HYPERTROPHY
AID  - 10.1136/heartjnl-2012-303148a.13
DP  - 2012 Nov 01
TA  - Heart
PG  - A4--A5
VI  - 98
IP  - Suppl 5
4099  - http://heart.bmj.com/content/98/Suppl_5/A4.4.short
4100  - http://heart.bmj.com/content/98/Suppl_5/A4.4.full
SO  - Heart2012 Nov 01; 98
AB  - 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 mm2 in untreated cells (n=300 p<0.01). Pre-treatment with RIC-superfusate/RIC-serum significantly reduced ET-1 induced hypertrophy from 19.8±0.8 to 14.7±0.6mm2 and 23.6±1.5 to 16.1±1.1mm2 respectively (n=300 p<0.01). RIC-superfusate caused a significant decrease in ET-1 induced expression of α-actin (fold-change 8.0±0.4 to 1.7±0.1, n=4 p<0.01), βMHC (6.5±0.5 to 2.5±0.3, n=4 p<0.01), BNP (1.3±0.3 to 0.4±0.2, n=4 p<0.05) and ms−1 (31.6±2.7 to 13.0±1.4, n=4 p<0.01) after 48 h. RIC-serum significantly reduced ET-1 induced expression of βMHC (7.7±1.0 to 3.9±0.5, n=4 p<0.05) and ms−1 (15.4±2.7 to 7.0±0.7, n=4 p<0.05) after 48 h. 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.