title: Evidence for the delayed effect in human ischemic preconditioning: prospective multicenter study for preconditioning in acute myocardial infarction.
abstract: OBJECTIVE
  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 < or = -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.
authors.affiliation: Second Department of Internal Medicine, Gifu University School of Medicine, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Noda
authors.forename: S
authors.initials: S
authors.lastname: Minatoguchi
authors.forename: K
authors.initials: K
authors.lastname: Fujii
authors.forename: M
authors.initials: M
authors.lastname: Hori
authors.forename: T
authors.initials: T
authors.lastname: Ito
authors.forename: K
authors.initials: K
authors.lastname: Kanmatsuse
authors.forename: M
authors.initials: M
authors.lastname: Matsuzaki
authors.forename: T
authors.initials: T
authors.lastname: Miura
authors.forename: H
authors.initials: H
authors.lastname: Nonogi
authors.forename: M
authors.initials: M
authors.lastname: Tada
authors.forename: M
authors.initials: M
authors.lastname: Tanaka
authors.forename: H
authors.initials: H
authors.lastname: Fujiwara
mesh_terms: D000787:Angina Pectoris / Q000175:diagnosis; D015906:Angioplasty, Balloon, Coronary; D006328:Cardiac Catheterization; D017023:Coronary Angiography; D003402:Creatine Kinase / Q000097:blood; D003937:Diagnosis, Differential; D005260:Female; D015637:Gated Blood-Pool Imaging; D006801:Humans; D019157:Ischemic Preconditioning, Myocardial; D008297:Male; D008875:Middle Aged; D009200:Myocardial Contraction; D009203:Myocardial Infarction / Q000175:diagnosis / Q000201:enzymology / Q000503:physiopathology / Q000628:therapy*; D011446:Prospective Studies; D013318:Stroke Volume; D016896:Treatment Outcome; D016277:Ventricular Function, Left
chemical_list: D003402:Creatine Kinase