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

DONATO M; BUCHHOLZ B; RODRÍGUEZ M; PEREZ V; INSERTE J; GARCIA-DORADO D; GELPI RJ

EXPERIMENTAL PHYSIOLOGY.

WILEY-BLACKWELL PUBLISHING, INC

Lugar: Londres; Año: 2013 vol. 98 p. 425 - 434

0958-0670

This investigation was designed to determine the participation of the vagus nerve andmuscarinic receptors in the remote ischemic preconditioning (rIPC) mechanism.New Zealand rabbits were anesthetized, and the femoral artery was dissected. After 30min of monitoring, the hearts were isolated and subjected to 30 min of global no-flowischemia and 180 min of reperfusion (non-rIPC group). The ventricular function wasevaluated considering the left ventricular developed pressure and the left ventricularend diastolic pressure. In rIPC group, the rabbits were subjected to a three-cycle hindlimb ischemia (5 min) and reperfusion (5 min) and the same protocol used in non-rIPCgroup was then repeated. In order to evaluate the afferent neural pathway during therIPC protocol, we performed two different groups: one in which the femoral and sciaticnerves were sectioned and the other in which the spinal cord was sectioned (T9-T10level). To study the efferent neural pathway during rIPC protocol, the vagus nerve wassectioned and, in a separated group, atropine was administered. The effect of vagalstimulation was also evaluated. An infarct size of 40.8±3.1% was obtained in non-rIPCgroup whereas in rIPC group, the infarct size decreased to 16.4±3.5% (p<0.01). Duringpreconditioning protocol, the vagus nerve section and the atropine administration eachabolished the effect of rIPC on infarct size. Vagal stimulation mimicked the effect ofrIPC, decreasing infarct size to 15.2±4.7% (p<0.01). There was a trend for attenuationof the rIPC protection that was not statistically significant with the sections of femoraland sciatic nerves. However, we demonstrated the presence of a neural afferentpathway since the spinal cord section completely abolished the effect of rIPC on infarctsize. In conclusion, rIPC activates a neural afferent pathway and the cardioprotective signalreaches the heart through the vagus nerve (efferent pathway) and acetylcholineactivates the IPC phenomenon when acting on the muscarinic receptors.