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J Am Coll Cardiol, 2000; 35:345-351
© 2000 by the American College of Cardiology Foundation
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CLINICAL STUDIES

Three minute, but not one minute, ischemia and nicorandil have a preconditioning effect in patients with coronary artery disease

Tetsuo Matsubara, MD* {dagger}, Shinya Minatoguchi, MD{dagger}, Hitoshi Matsuo, MD* {dagger}, Kenji Hayakawa, MD* {dagger}, Tomonori Segawa, MD* {dagger}, Yukihiko Matsuno, MD* {dagger}, Sachiro Watanabe, MD* {dagger}, Masazumi Arai, MD*, Yoshihiro Uno, MD{dagger}, Masanori Kawasaki, MD* {dagger}, Toshiyuki Noda, MD{dagger}, Genzou Takemura, MD{dagger}, Kazuhiko Nishigaki, MD{dagger} and Hisayoshi Fujiwara, MD{dagger}

* Department of Cardiology, Gifu Prefectural Hospital, Gifu, Japan
{dagger} Second Department of Internal Medicine, Gifu University School of Medicine, Gifu, Japan

Manuscript received December 31, 1998; revised manuscript received August 3, 1999, accepted October 18, 1999.

Reprint requests and correspondence: Dr. Hisayoshi Fujiwara, Second Department of Internal Medicine, Gifu University School of Medicine, 40 Tsukasa-Machi, Gifu 500, Japan

OBJECTIVES

This study focused on 1) the determination of the optimal preconditioning (PC) duration, and 2) the protective effect of nicorandil (NC), a hybrid nitrate with a KATP channel opening effect, during a percutaneous transluminal coronary angioplasty (PTCA) model in humans.

BACKGROUND

The ischemic PC effect is induced in 180 s ischemia, but not in 120 s ischemia in rabbit hearts. However, the duration of ischemia that induces PC effect and the role of the KATP channel in the PC effect in humans are still unclear.

METHODS

Forty-six patients with stable angina were randomly allocated to four groups: the duration of the first inflation as PC ischemia was 60 s in the PC60 group (n = 12), and 180 s in the PC180 group (n = 12). In the other groups, NC (80 µg/kg) was intravenously given for 1 min in the NC group (n = 12), and isosorbide dinitrate (ISDN) (40 µg/kg) was given in the ISDN group (n = 10). Five minutes after first inflation or drug administration, a second inflation was conducted for 120 s in each group. In the ECG, the lead with the largest shift in ST segment (deltaST max), and the sum of elevated ST levels in all leads (sigmaST) were determined.

RESULTS

In the PC60 group, no significant difference was observed in either deltaST max or sigmaST between the first and second inflation. However, the second inflation in the PC180 group showed significantly lower levels of deltaST max and sigmaST compared with those of the first inflation. In the NC group, both deltaST max and sigmaST measured at 30 s and 60 s after balloon inflation were significantly lower than those of the first inflation in the PC60 and PC180 control groups. In the ISDN group, no significant difference was observed in deltaST max or sigmaST.

CONCLUSION

In human PTCA models, a PC effect is observed in 180 s ischemia, but not in 60 s ischemia. A pharmacological PC effect is induced by NC, a KATP channel opener with a nitrate-like effect but not ISDN. This suggests that the opening of KATP channels plays an important role in the protecting effect of NC.

Abbreviations and Acronyms
  AMI = acute myocardial infarction
  ANOVA = analysis of variance
  ISDN = isosorbide dinitrate
  LAD = left anterior descending artery
  NC = nicorandil
  PC = preconditioning
  PTCA = percutaneous transluminal coronary angioplasty




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