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CLINICAL STUDIES

Evidence for the delayed effect in human ischemic preconditioning

Prospective multicenter study for preconditioning in acute myocardial infarction

Toshiyuki Noda, MD^*, Shinya Minatoguchi, MD^*, Kenshi Fujii, MD^a, Masatsugu Hori, MD, Takayuki Ito, MD, Katsuo Kanmatsuse, MD, Masunori Matsuzaki, MD^||, Tetsuji Miura, MD^¶, Hiroshi Nonogi, MD^#, Michihiko Tada, MD, Masaru Tanaka, MD^** and Hisayoshi Fujiwara, MD^*

^a Second Department of Internal Medicine, Gifu University School of Medicine, Gifu, Japan
^* Division of Cardiology, Sakurabashi Watanabe Hospital, Osaka, Japan
The First Department of Medicine, Osaka University School of Medicine, Osaka, Japan
The Second Department of Internal Medicine, Nagoya University School of Medicine, Nagoya, Japan
Department of Cardiology, Surugadai Nihon University Hospital, Tokyo, Japan
^|| The Second Department of Internal Medicine, Yamaguchi University School of Medicine, Ube, Japan
^¶ The Second Department of Internal Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan
^# Division of Cardiology, Department of Internal Medicine, National Cardiovascular Center, Osaka, Japan
^** The Third Department of Internal Medicine, Kyoto University, Kyoto, Japan

Manuscript received December 18, 1998; revised manuscript received July 1, 1999, accepted August 30, 1999.

Reprint requests and correspondence: Dr. Hisayoshi Fujiwara, Second Department of Internal Medicine, Gifu University School of Medicine, 40 Tsukasa-machi, Gifu 500-8705, Japan
gifuim-gif{at}umin.ac.jp

OBJECTIVES

This study aimed to investigate prospectively the protective effect of a first preinfarction angina attack against acute myocardial infarction (AMI) in human hearts without significant collaterals.

BACKGROUND

Several retrospective studies and the prospective studies have demonstrated the existence of the preconditioning (PC) effect in humans. However, collaterals were not examined in the prospective studies. In animal models, the PC effect on myocardial infarct size appears soon after PC reperfusion (classic) but disappears within 1 to 2 h. It then reappears 24 to 48 h after reperfusion (the delayed PC effect). Meanwhile, the PC effect on stunning appears 12 h after PC reperfusion (the delayed PC effect). The concept of the classic and delayed PC effects has not been investigated in human AMI studies. If the above concept is also correct in humans, the infarct size and/or impairment of the left ventricular function should be inversely correlated with the time interval between the first preinfarction angina attack and the onset of AMI when that time interval is limited to between 2 and 48 h.

METHODS

The subjects were 25 patients with first AMI of the proximal left anterior descending artery who underwent successful direct percutaneous transluminal coronary angioplasty (PTCA) 2 to 6 h after the onset and with no (or poor) collateral circulation (grade 0 or 1). They were divided into two groups: preinfarction angina (PA)(+) group: 11 patients with new onset preinfarction angina from 2 to 48 h before the onset, PA(–) group: 14 patients without angina before infarction. Peak creatine kinase (CK) and cumulative CK were examined, and the left ventricular ejection fraction (LVEF) and the regional wall motion (RWM) were determined from the left ventriculograms during the acute (immediately after the coronary reperfusion) and chronic (four weeks after the onset of AMI) phases. The RWM index (RWMI) was then calculated as the mean motion of chords (standard deviation [SD]/chord) lying in the area of chords of RWM –2 SD in the acute phase (ischemic risk area).

RESULTS

The increase in the RWMI between the acute and chronic phases was significantly larger in the PA(+) group than in the PA(–) group (1.55 ± 1.32 and 0.69 ± 0.75, p < 0.05, respectively) although no significant difference in the enzymatic infarct size was seen between the two groups. The increases in the LVEF and the RWMI were significantly correlated with the time interval from the first preinfarction angina attack to the onset of AMI (r = 0.622, p < 0.05 and r = 0.646, p < 0.05, respectively), but the enzymatic infarct size was not.

CONCLUSIONS

The beneficial effect of preinfarction angina on left ventricular wall motion, independently of collateral flows, indicates the existence of the PC effect in humans. The greater protective effect of a longer time interval between angina pectoris and AMI suggests that the protection is due to a delayed PC effect.

Abbreviations and Acronyms   AMI = acute myocardial infarction   CK = creatine kinase   LVEDV = left ventricular end-diastolic volume   LVEF = left ventricular ejection fraction   PA = preinfarction angina   PC = preconditioning   PTCA = percutaneous transluminal coronary angioplasty   RWM = regional wall motion   RWMI = regional wall motion index   SD = standard deviation

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