Evidence of pharmacologic preconditioning during PTCA by intravenous pretreatment with ATP-sensitive K+ channel opener nicorandil

Eur Heart J. 2003 Jul;24(14):1296-303. doi: 10.1016/s0195-668x(03)00202-1.

Abstract

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.

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

Publication types

  • Clinical Trial
  • Comparative Study
  • Randomized Controlled Trial

MeSH terms

  • Aged
  • Angioplasty, Balloon, Coronary* / methods
  • Calcium Channel Agonists / therapeutic use*
  • Collateral Circulation
  • Coronary Stenosis / therapy
  • Female
  • Humans
  • Ischemic Preconditioning, Myocardial / methods*
  • Male
  • Middle Aged
  • Myocardial Ischemia / diagnostic imaging
  • Myocardial Ischemia / drug therapy*
  • Myocardial Revascularization
  • Nicorandil / therapeutic use*
  • Organophosphorus Compounds
  • Organotechnetium Compounds
  • Radionuclide Imaging
  • Radiopharmaceuticals
  • Vasodilator Agents / therapeutic use*

Substances

  • Calcium Channel Agonists
  • Organophosphorus Compounds
  • Organotechnetium Compounds
  • Radiopharmaceuticals
  • Vasodilator Agents
  • Nicorandil
  • technetium tc-99m tetrofosmin