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.

Inhibitory effects of bezoar bovis on intimal formation and vascular smooth muscle cell proliferation in rat.

Intimal formation of animal carotid arteries induced by balloon endothelial denudation has been considered to be an "accelerated atherosclerosis" model and used in primary screening methods to evaluate natural drugs and chemical candidates. The aim of the present study was to examine whether intimal formation is prevented by Bezoar Bovis (dried cattle gallbladder stones: Niuhuang in Chinese and Go-o in Japanese), which has been used to prevent heart palpitation in patients with hypertension. The intimal-to-medial area ratio in rat carotid arteries 7 days after balloon endothelial denudation was significantly reduced by oral administration of Bezoar Bovis. Bezoar Bovis also suppressed vascular smooth muscle cells (VSMCs) proliferation, which is thought to play important roles in the intimal formation after endothelial damage and also atherosclerosis resulting from long-term inappropriate lifestyle. The present findings suggest that Bezoar Bovis may be useful for preventing atherosclerosis and for protection against restenosis after percutaneous coronary intervention, for which effective reduction method is not currently available.