Vagal stimulation suppresses ischemia-induced myocardial interstitial myoglobin release.
OBJECTIVE
To evaluate vagal stimulation-mediated myocardial protection against ischemia and reperfusion in in vivo ischemic myocardium.


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).


RESULTS
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).


CONCLUSIONS
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.
Kawada
Toru
T
Department of Cardiovascular Dynamics, Advanced Medical Engineering Center, National Cardiovascular Center Research Institute, Osaka, Japan. torukawa@res.ncvc.go.jp
Yamazaki
Toji
T
Akiyama
Tsuyoshi
T
Kitagawa
Hirotoshi
H
Shimizu
Shuji
S
Mizuno
Masaki
M
Li
Meihua
M
Sugimachi
Masaru
M
D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D001919:Bradycardia / Q000378:metabolism / Q000503:physiopathology; D002304:Cardiac Pacing, Artificial; D002415:Cats; D004195:Disease Models, Animal; D004599:Electric Stimulation Therapy; D006321:Heart / Q000187:drug effects; D017551:Microdialysis; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism*; D009211:Myoglobin / Q000378:metabolism*; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D000081082:Phosphoinositide-3 Kinase Inhibitors; D014630:Vagus Nerve / Q000187:drug effects / Q000378:metabolism*; D000077191:Wortmannin
D000730:Androstadienes; D009211:Myoglobin; D010726:Phosphodiesterase Inhibitors; D000081082:Phosphoinositide-3 Kinase Inhibitors; D000077191:Wortmannin