Optimal intervention time of vagal stimulation attenuating myocardial ischemia/reperfusion injury in rats.

OBJECTIVE

To determine the optimal intervention time of the vagal stimulation (VS) attenuating myocardial ischemia/reperfusion injury (IRI).

METHODS

One hundred and twenty male SD rats were randomly allocated into six groups: sham group, IRI group, the VS performed at 15 min of ischemia (VSI15) group, the VS performed immediately before reperfusion (VSR0) group, the VS performed at 30 min of reperfusion (VSR30) group, and the VS performed at 60 min of reperfusion (VSR60) group. Rats in each group were further allocated into subgroups A and B. In each group, the hemodynamics and ventricular arrhythmias were continuously observed. In the subgroup A, serum inflammatory cytokine levels were tested, and infarct size was assessed. In the subgroup B, myocardial inflammatory cytokine levels in both ischemic and non-ischemic regions were assayed.

RESULTS

As compared to the IRI, VSR0, VSR30 and VSR60 groups, infarct size, serum HMGB-1 and ICAM-1 levels at 120 min of reperfusion, myocardial HMGB-1, IL-1 and IL-6 levels in non-ischemic region, myocardial ICAM-1 level in ischemic region were all significantly decreased in the VSI15 group. Compared with the IRI group, myocardial IL-10 levels in both ischemic and non-ischemic regions were significantly increased in the VSI15 group. Compared to the IRI, VSR0, VSR30 and VSR60 groups, incidence and score of ventricular arrhythmia during initial reperfusion were significantly decreased in the VSI15 group.

CONCLUSIONS

The VS performed at 15 min of ischemia provides the best protection against myocardial IRI. Also, early modulation on inflammatory responses caused by myocardial IRI may contribute to this best cardioprotection.