Tumour necrosis factor-α and its receptors in the beneficial effects of vagal stimulation after myocardial infarction in rats.

1. Acute myocardial infarction (AMI) often activates the sympathetic system and inhibits the vagal system. Long-term vagal nerve stimulation (VNS) exerts several beneficial effects on the ischaemic heart, including an anti-inflammatory effect. The aim of the present study was to investigate whether short-term VNS during AMI could inhibit tumour necrosis factor (TNF)-α expression and the effect of TNF receptor (TNFR), key components in inflammatory responses to AMI, in a rodent model. 2. Adult male Sprague-Dawley rats were divided into four groups, namely a control (C), VNS (S), AMI (M) and an AMI group subjected to prior VNS (MS). In the S and MS groups, the right vagus nerve was stimulated electrically for 4 h; in the M and MS groups, AMI was induced by occlusion of the left anterior descending coronary artery. Haemodynamic data were monitored continuously using a multichannel physiological recorder. Lactate dehydrogenase (LDH) leakage, creatine kinase (CK) leakage and infarct size were determined. The expression of TNF-α and its receptors were analysed by reverse transcription-polymerase chain reaction, western blotting and ELISA. 3. Compared with the control group, rats in the M group had low blood pressure, high left ventricular (LV) end-diastolic pressure, a depressed maximum dP/dt of LV pressure, higher LDH and CK leakage, a larger infarct size, increased TNF-α levels and an increased TNFR1/TNFR2 ratio. However, these presumably harmful effects of AMI were all significantly ameliorated by VNS during AMI (MS group). 4. In conclusion, VNS can rectify ischaemia-induced cardiac dysfunction partly via inhibition of a TNF-α-mediated signalling pathway.