Role of the parasympathetic nervous system in cardioprotection by remote hindlimb ischaemic preconditioning

Abstract

New findings r What is the central question of this study?Ischaemia-reperfusion of peripheral tissues protects the heart from subsequent myocardial ischaemia-reperfusion-induced injury and cardiac dysfunction, a phenomenon referred to as 'remote ischaemic preconditioning' (rIPC). This study addressed whether activation of sensory afferent nerves in the ischaemic hindlimb and vagal efferent nerves innervating the heart mediate rIPC. This investigation was designed to determine the participation of the vagus nerve and muscarinic receptors in the remote ischaemic preconditioning (rIPC) mechanism. New Zealand rabbits were anaesthetized, and the femoral artery was dissected. After 30 min of monitoring, the hearts were isolated and subjected to 30 min of global no-flow ischaemia and 180 min of reperfusion (nonrIPC group). The ventricular function was evaluated, considering the left ventricular developed pressure and the left ventricular end-diastolic pressure. In the rIPC group, the rabbits were subjected to three cycles of hindlimb ischaemia (5 min) and reperfusion (5 min), and the same protocol as that used in non-rIPC group was then repeated. In order to evaluate the afferent neural pathway during the rIPC protocol we used two groups, one in which the femoral and sciatic nerves were sectioned and the other in which the spinal cord was sectioned (T9-T10 level). To study the efferent neural pathway during the rIPC protocol, the vagus nerve was sectioned and, in another group, atropine was administered. The effect of vagal stimulation was also evaluated. An infarct size of 40.8 ± 3.1% was obtained in the non-rIPC group, whereas in rIPC group the infarct size decreased to 16.4 ± 3.5% (P < 0.05). During the preconditioning protocol, the vagus nerve section and the atropine administration each abolished the effect of rIPC on infarct size. Vagal stimulation mimicked the effect of rIPC, decreasing infarct size to 15.2 ± 4.7% (P < 0.05). Decreases in infarct size were accompanied by improved left ventricular function.M. Donato and B. Buchholz contributed equally to this manuscript.

Molecular Basis of Cardioprotection

“…The activation of the peripheral sensory fibers involves activation of the PKCγ isoform. 439 In some studies, activation of the autonomic nervous system through spinal and supraspinal reflexes [435][436][437]442 was mandatory to reduce IS in the ischemic/reperfused myocardium, 32,92,434,435,437,443 in others it was not. 432,444 Of importance, humoral transfer of protection with plasma or dialysate obtained after the peripheral preconditioning cycles to another individual or individual heart, even across species, is possible and highlights the functional importance of the humoral transfer signal.…”

Across-Species Transfer of Protection by Remote Ischemic Preconditioning With Species-Specific Myocardial Signal Transduction by Reperfusion Injury Salvage Kinase and Survival Activating Factor Enhancement Pathways

“…Also, an additional involvement of neuronal pathways either during the initiation of the RIPC stimulus, its transfer, or the installation of protection in the pig myocardium cannot be excluded. 45 …”

Lactation protects against myocardial ischemia-reperfusion injury in rats

“…The researchers found that cardioprotective effects of VNS including reduced infarct size and decreased ventricular fibrillation episodes were abolished by muscarinic blockade (38). On the other hand, the protective signal of remote IPC reaches the heart through the vagus nerve and activation of muscarinic receptors (9).…”