Effects of nicorandil on cardiac sympathetic nerve activity after reperfusion therapy in patients with first anterior acute myocardial infarction.
OBJECTIVE
Ischaemic preconditioning (PC) is a cardioprotective phenomenon in which short periods of myocardial ischaemia result in resistance to decreased contractile dysfunction during a subsequent period of sustained ischaemia. Nicorandil, an ATP-sensitive potassium channel opener, can induce PC effects on sympathetic nerves during myocardial ischaemia. However, its effects on cardiac sympathetic nerve activity (CSNA) and left ventricular remodelling have not been determined. In this study, we sought to determine whether nicorandil administration improves CSNA in patients with acute myocardial infarction (AMI).


METHODS
We studied 58 patients with first anterior AMI, who were randomly assigned to receive nicorandil (group A) or isosorbide dinitrate (group B) after primary coronary angioplasty. The nicorandil or isosorbide dinitrate was continuously infused for >48 h. The extent score (ES) was determined from 99mTc-pyrophosphate scintigraphy, and the total defect score (TDS) was determined from 201Tl scintigraphy 3-5 days after primary angioplasty. The left ventricular end-diastolic volume (LVEDV) and left ventricular ejection fraction (LVEF) were determined by left ventriculography 2 weeks later. The delayed heart/mediastinum count (H/M) ratio, delayed TDS and washout rate (WR) were determined from 123I-meta-iodobenzylguanidine (MIBG) images 3 weeks later. The left ventriculography results were re-examined 6 months after treatment.


RESULTS
Fifty patients originally enrolled in the trial completed the entire protocol. After treatment, no significant differences were observed in ES or left ventricular parameters between the two groups. However, in group A (n=25), the TDSs determined from 201Tl and 123I-MIBG were significantly lower (26+/-6 vs 30+/-5, P<0.01, and 32+/-8 vs 40+/-6, P<0.0001, respectively), the H/M ratio significantly higher (1.99+/-0.16 vs 1.77+/-0.30, P<0.005) and the WR significantly lower (36%+/-8% vs 44%+/-12%, P<0.005) than in group B (n=25). Moreover, 6 months after treatment, LVEDV and LVEF were better in group A than in group B.


CONCLUSIONS
These findings indicate that nicorandil can have beneficial effects on CSNA and left ventricular remodelling in patients with first anterior AMI.
Kasama
Shu
S
Department of Cardiovascular Medicine, Gunma University School of Medicine, 3-39-15, Showa-machi, Maebashi, 371-0034, Japan. s-kasama@bay.wind.ne.jp
Toyama
Takuji
T
Kumakura
Hisao
H
Takayama
Yoshiaki
Y
Ichikawa
Shuichi
S
Suzuki
Tadashi
T
Kurabayashi
Masahiko
M
D019797:3-Iodobenzylguanidine; D015906:Angioplasty, Balloon, Coronary; D005260:Female; D006801:Humans; D007548:Isosorbide Dinitrate / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000150:complications / Q000000981:diagnostic imaging* / Q000188:drug therapy* / Q000601:surgery; D020108:Nicorandil / Q000008:administration & dosage*; D011379:Prognosis; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals; D013564:Sympathetic Nervous System / Q000187:drug effects*; D016896:Treatment Outcome; D014665:Vasodilator Agents / Q000008:administration & dosage; D018487:Ventricular Dysfunction, Left / Q000000981:diagnostic imaging* / Q000188:drug therapy* / Q000209:etiology / Q000601:surgery
D019275:Radiopharmaceuticals; D014665:Vasodilator Agents; D020108:Nicorandil; D019797:3-Iodobenzylguanidine; D007548:Isosorbide Dinitrate