Vagal stimulation suppresses ischemia-induced myocardial interstitial myoglobin release

Aims: To evaluate vagal stimulation-mediated myocardial protection against ischemia and reperfusion in in vivo ischemic myocardium. Main methods: We measured myocardial interstitial myoglobin levels in the ischemic region using a cardiac microdialysis technique in anesthetized and vagotomized cats. We occluded the left anterior descending coronary artery (LAD) for 60 min and reperfused it for 60 min (VX group, n = 6). The effects of bilateral vagal stimulation (10 V, 5 Hz, 1-ms pulse duration), initiated immediately after LAD occlusion, were examined (VS group, n = 6). To examine the involvement of phosphatidylinositol 3-kinase (PI3K), vagal stimulation was performed after pretreatment with a PI3K inhibitor wortmannin (0.6 mg/kg, i.v.) (VS-W group, n = 6). To examine the contribution of bradycardia, vagal stimulation was performed with fixed-rate ventricular pacing (VS-P group, n = 6). Key findings: The average myoglobin level during the ischemic period was 1170 ± 141 in VX (in ng/ml, mean ± SE), which was significantly attenuated in VS (466 ± 87, P < 0.05) and VS-W (613 ± 124, P < 0.05) but not in VS-P (953 ± 203). Reperfusion increased the myoglobin level to 2500 ± 544 in VX, whereas it was suppressed in VS (824 ± 213, P < 0.05) and VS-W (948 ± 315, P < 0.05) but not in VS-P (1710 ± 253). Significance: Vagal stimulation, initiated immediately after LAD occlusion, attenuated the myocardial injury. Moreover, bradycardia, independent of PI3K pathway, plays a significant role in vagally induced cardioprotection during acute myocardial ischemia.