Evidence of pharmacologic preconditioning during PTCA by intravenous pretreatment with ATP-sensitive K+ channel opener nicorandil.
BACKGROUND
It is not known whether pretreatment with nicorandil, an ATP-sensitive K+ channel (K(ATP)channel) 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 80 g/kg nicorandil 5 min 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 (sigmaST).


RESULTS
SigmaST levels were significantly reduced in patients with nicorandil pretreatment compared with control patients (control:1.89+/-0.85 mV nicorandil:1.24+/-0.57 mV, 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 sigmaST in both groups (nicorandil group R(2)=0.505, control group R(2)=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 sigmaST, suggesting a cellular protective effect against ischaemia by nicorandil, independent of myocardial blood flow.


CONCLUSIONS
Nicorandil pretreatment resulted in the induction of myocardial preconditioning independent of the severity of ischaemia.
Matsuo
Hitoshi
H
Gifu Prefectural Hospital, Gifu, Japan.
Watanabe
Sachiro
S
Segawa
Tomonori
T
Yasuda
Shinji
S
Hirose
Takeshi
T
Iwama
Makoto
M
Tanaka
Shinichiro
S
Yamaki
Takahiko
T
Matsuno
Yukihiko
Y
Tomita
Masaaki
M
Minatoguchi
Shinya
S
Fujiwara
Hisayoshi
H
D000368:Aged; D015906:Angioplasty, Balloon, Coronary / Q000379:methods; D002120:Calcium Channel Agonists / Q000627:therapeutic use*; D003097:Collateral Circulation; D023921:Coronary Stenosis / Q000628:therapy; D005260:Female; D006801:Humans; D019157:Ischemic Preconditioning, Myocardial / Q000379:methods*; D008297:Male; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000000981:diagnostic imaging / Q000188:drug therapy*; D009204:Myocardial Revascularization; D020108:Nicorandil / Q000627:therapeutic use*; D009943:Organophosphorus Compounds; D015609:Organotechnetium Compounds; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals; D014665:Vasodilator Agents / Q000627:therapeutic use*
D002120:Calcium Channel Agonists; D009943:Organophosphorus Compounds; D015609:Organotechnetium Compounds; D019275:Radiopharmaceuticals; D014665:Vasodilator Agents; D020108:Nicorandil; C078700:technetium tc-99m tetrofosmin