Ischemia-induced norepinephrine release, but not norepinephrine-derived free radicals, contributes to myocardial ischemia-reperfusion injury.
BACKGROUND
Norepinephrine (NE)-derived free radicals may contribute to myocyte injury after ischemia -reperfusion, so the influence of sympathetic denervation on myocardial ischemia - reperfusion injury was investigated in the present study.


RESULTS
Cardiac sympathetic denervation was produced in Wistar rats by a solution of 10% phenol 1 week before ischemia. Atenolol (0.5 mg/kg) was intravenously administered 10 min before the coronary occlusion. The left coronary artery was occluded for 30 min and thereafter reperfused. Cardiac interstitial fluid was collected by a microdialysis probe and free radicals in dialysate were determined by electron paramagnetic resonance (EPR) spin trapping, using 5,5-dimethyl-1-pyrroline-N-oxide as a spin trap. The ratio of infarct size to the ischemic area at risk (I/R) was decreased in both the phenol and atenolol groups compared with control (28.5+/-11.3, 31.8+/-10.7 vs 50.6+/-14.7%, p<0.05). During the coronary occlusion, concentrations of interstitial NE increased markedly in the control and atenolol groups, but was unchanged in the phenol group. EPR signal intensity (relative value to internal standard) was maximal at 1 h after reperfusion and was similar in the phenol and control groups (0.32+/-0.15 vs 0.45+/-0.19).


CONCLUSIONS
Cardiac denervation protected myocyte against ischemia-reperfusion injury through decreasing direct NE toxicity, but not through decreasing NE-derived free radicals.
Nonomura
Makoto
M
The Second Department of Internal Medicine, Toyama Medical and Pharmaceutical University, Japan.
Nozawa
Takashi
T
Matsuki
Akira
A
Nakadate
Teruo
T
Igarashi
Norio
N
Kato
Bun-ichi
B
Fujii
Nozomu
N
Igawa
Akihiko
A
Asanoi
Hidetsugu
H
Kondo
Takashi
T
Inoue
Hiroshi
H
D000818:Animals; D004578:Electron Spin Resonance Spectroscopy; D005609:Free Radicals / Q000032:analysis / Q000378:metabolism*; D008297:Male; D017202:Myocardial Ischemia / Q000378:metabolism*; D015428:Myocardial Reperfusion Injury / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
D005609:Free Radicals; D009638:Norepinephrine