018 The interaction between the humoural and neural pathways underlying remote ischaemic preconditioning

Abstract

<h3>Introduction</h3> Remote ischaemic preconditioning (RIPC) is a clinically amenable therapeutic intervention that has been demonstrated to limit myocardial infarct size. However, the underlying cardioprotective mechanisms remain unclear. We hypothesised that RIPC utilises both humoural and neural pathways to convey the cardioprotective signal from the preconditioned remote organ to the heart. <h3>Methods</h3> C57BL/6 mice (10–12-weeks old, male) were anaesthetised and subjected to in vivo 30 min left anterior descending coronary artery ischaemia followed by 120 min of myocardial reperfusion, at the end of which myocardial infarct size was measured by Evan9s blue and triphenyltetrazolium chloride (TTC) dual-staining and expressed as a percentage of the area at risk (AAR). RIPC was induced by three cycles of 5 min left femoral artery occlusion interspersed with 5 min reperfusion before prolonged myocardial ischaemia with or without femoral vein occlusion (to assess the humoural pathway), femoral nerve resection and/or sciatic nerve resection (to assess the neural pathway). <h3>Results</h3> RIPC resulted in a smaller myocardial infarct size when compared to control (21.6±1.6% vs 51.5±4.8% in control; p&lt;0.05; N=10/group). However, occluding the femoral vein completely abolished the infarct-limiting effect of RIPC 45.0±5.2% vs 21.6±1.6% with RIPC; p&lt;0.05; N=10/group). Similarly, combined femoral and sciatic nerve resection also abolished the cardioprotective effect of RIPC (51.6±3.5% vs 21.6±1.6% with RIPC; p&lt;0.05; N=10/group). Interestingly, femoral nerve or sciatic nerve resection alone only partially abolished the infarct-limiting effect of RIPC (39.0±2.8% with femoral nerve resection, 34.1±3.0% with sciatic nerve resection vs 21.6±1.6% with RIPC; p&lt;0.05; N&gt;9/group). <h3>Conclusions</h3> Remote limb ischaemic preconditioning reduces myocardial infarct size in the mice in a manner which is dependent on both cardioprotective humoural factor(s) and an intact neural pathway.