Right vs left vagus and cardioprotection conferred by remote ischaemic pre- and perconditioning

Abstract

Purpose: Myocardial ischaemia/reperfusion injury can be significantly reduced by remote ischaemic conditioning (RIc) when episodes of limb ischaemia/reperfusion are applied prior (remote ischaemic preconditioning, RIPrec) to myocardial ischaemia (MI), during MI (remote ischaemic perconditioning, RIPerc) and even with a significant delay after the onset of myocardial reperfusion (remote ischaemic postconditioning, RIPost). Cardioprotection induced by RIPrec is abolished by bilateral vagotomy or silencing of vagal preganglionic neurones in the brainstem. In this study we determined whether cardiac innervation provided by the right and the left vagus are equally important in mediating cardioprotection established by RIPrec and RIPerc.Methods: Rat model of myocardial ischaemia/reperfusion injury involved 30 min of left coronary artery occlusion followed by 120 min of reperfusion. RIPrec (n=10) and RIPerc (n=10) were induced by 15 min occlusion of both femoral arteries applied 25 min prior to and 10 min after the onset of MI, respectively. Sham-RIc procedure involved dissection of both femoral arteries without occlusion (n=8). Bilateral or unilateral right/left vagotomies were performed 40 min before the onset of MI (n=6-10).Results: There were no significant differences in haemodynamic parameters between the groups of animals during the experiments. RIPrec and RIPerc conferred potent cardioprotection as evident from significant reductions in infarct size (19±5% and 21±7%, respectively vs 46±7% in sham-RIc group; p<0.001). Bilateral vagotomy abolished cardioprotection established by either RIPrec or RIPerc. Unilateral right or left vagotomy abolished cardioprotection induced by RIPerc (38±7% and 38±9%, respectively; p<0.001) but had no effect on cardioprotection established by RIPrec (30±7% and 31±13%, respectively; p=NS).Conclusions: These data indicate that the activity of either right or left vagus nerve is sufficient to mediate cardioprotection established by remote ischaemic preconditioning. Functional integrity of both nerves is required to establish cardioprotection when remote conditioning stimulus is applied during myocardial ischaemia.