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European Heart Journal 2003 24(14):1296-1303; doi:10.1016/S0195-668X(03)00202-1
Copyright © 2003 by the European Society of Cardiology.
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Evidence of pharmacologic preconditioning during PTCA by intravenous pretreatment with ATP-sensitive K+ channel opener nicorandil

Hitoshi Matsuoa,*, Sachiro Watanabea, Tomonori Segawaa, Shinji Yasudaa, Takeshi Hirosea, Makoto Iwamaa, Shinichiro Tanakaa, Takahiko Yamakia, Yukihiko Matsunoa, Masaaki Tomitaa, Shinya Minatoguchib and Hisayoshi Fujiwarab,*

a Gifu Prefectural Hospital, Gifu, Japan
b The Second Department of Internal Medicine, Gifu University School of Medicine, Gifu, Japan

* Correspondence to: Hitoshi Matsuo MD, 4-6-1, Noishiki, Gifu City, Gifu Prefecture, 500, Japan. Tel: 81-58-246-1111; fax: 81-58-248-3805

E-mail address: matsuo{at}iri.rd.pref.gifu.jp

Received 2 November 2002; revised 13 February 2003; accepted 5 March 2003

Background It is not known whether pretreatment with nicorandil, an ATP-sensitive K+ channel (KATPchannel) opener, induces a preconditioning effect independent of increased collateral recruitment.

Methods Forty-four patients with angina who underwent percutaneous transluminal coronary angioplasty (PTCA) to proximal left anterior descending artery (LAD) stenosis were randomly allocated for pretreatment with an intravenous injection of 80g/kg nicorandil 5min before initial ballooning (n=22) or saline (n=22). 99mTc tetrofosmin was injected during balloon inflation, quantitative analysis of occlusion images by SPECT was conducted, and the defect severity score (SS) was calculated. An ECG was recorded during the 2-min inflation to calculate the sum of ST elevation ({Sigma}ST).

Results {Sigma}ST levels were significantly reduced in patients with nicorandil pretreatment compared with control patients (control:1.89±0.85mV nicorandil:1.24±0.57mV, p=0.0052). However, no difference was observed in defect severity (control: 79.0±32.5, nicorandil: 98.7±48.9 ns). A close correlation was observed between SS and {Sigma}ST in both groups (nicorandil group R2=0.505, control group R2=0.599). A multivariate regression model demonstrated that both defect severity (p<0.0001) and pretreatment with nicorandil (p<0.001) were significantly related to the level of {Sigma}ST, suggesting a cellular protective effect against ischaemia by nicorandil, independent of myocardial blood flow.

Conclusion Nicorandil pretreatment resulted in the induction of myocardial preconditioning independent of the severity of ischaemia.

Key Words: Angina pectoris • K+ channel opener • Ischemic preconditioning • Coronary angioplasty • Radionuclide imaging


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