title: Acute ischemic dysfunction alters coronary flow reserve in remote nonischemic regions: potential mechanical etiology identified in an acute canine model.
abstract: BACKGROUND
  Impaired coronary flow reserve (CFR) has been observed in remote nonischemic regions in patients after myocardial infarction. The mechanism for this impairment in remote nonischemic CFR remains undefined. This study evaluates the effect of progressive regional ischemic dysfunction on function in remote nonischemic regions, and the effect of the extent of dysfunction on remote nonischemic coronary flow and CFR.
  
  
  METHODS
  In an anesthetized open-chest canine model (n = 7) of acute progressive distal and proximal left anterior descending (LAD) coronary artery occlusion, regional myocardial thickening fraction and coronary flow and CFR were measured with Doppler probes. CFR was assessed by an intracoronary injection of 36 microg of adenosine. Changes in thickening fraction and CFR were evaluated for isovolumic, ejection, and diastolic phases. Changes in resting regional flow were also assessed using radiolabeled microspheres. The extent of the ischemic area was defined as regions of myocardium with endocardial microsphere blood flow less than 0.3 mL/min/g.
  
  
  RESULTS
  The ischemic area increased from 12% +/- 1% of left ventricle with distal occlusion to 30% +/- 2% of left ventricle with proximal occlusion (P < .001). The LAD thickening fraction decreased significantly from baseline (18% +/- 1%) to distal (-8% +/- 1%,) and proximal (-4% +/- 1%) occlusion (P < .001 for distal and proximal vs baseline). Isovolumic bulging in the LAD region was associated with a progressive increase in thickening fraction in the remote nonischemic left circumflex (LCX) artery region (baseline 12% +/- 1%; distal occlusion 15% +/- 2%, P = .014 vs baseline; proximal occlusion 17% +/- 2%, P = .02 vs baseline). Most of the increase in remote thickening fraction occurred during the isovolumic phase. There was no significant change in resting flow in remote nonischemic LCX regions or global hemodynamic parameters. However, there was a progressive decrease in remote nonischemic CFR (baseline 2.44 +/- 0.3), distal occlusion (2.19 +/- 0.31; P = .055 vs baseline), and proximal occlusion (1.79 +/- 0.22; P = 0.004 vs baseline, and P = .012 vs distal occlusion). A progressive decrease in CFR was noted in each phase of the cardiac cycle.
  
  
  CONCLUSIONS
  In a canine model of acute progressive distal and proximal coronary occlusion, we observed a progressive decrease in CFR in remote nonischemic regions concurrent with an increase in the extent of ischemia. The decrease in remote nonischemic CFR was associated with ischemia-induced isovolumic bulging, which placed the remote regions at a mechanical disadvantage. These observations suggest a potential mechanical etiology for the observed impairment in remote CFR. Alterations in remote nonischemic CFR during acute ischemia may have important clinical implications for perfusion scintigraphy.
authors.affiliation: Department of Medicine, Yale University School of Medicine, New Haven, Conn 06520-8042, USA.
authors.forename: E
authors.initials: E
authors.lastname: Daher
authors.forename: D P
authors.initials: DP
authors.lastname: Dione
authors.forename: E N
authors.initials: EN
authors.lastname: Heller
authors.forename: J
authors.initials: J
authors.lastname: Holahan
authors.forename: P
authors.initials: P
authors.lastname: DeMan
authors.forename: M
authors.initials: M
authors.lastname: Shen
authors.forename: J
authors.initials: J
authors.lastname: Hu
authors.forename: A J
authors.initials: AJ
authors.lastname: Sinusas
mesh_terms: D000818:Animals; D003326:Coronary Circulation; D004285:Dogs; D006439:Hemodynamics; D017202:Myocardial Ischemia / Q000503:physiopathology*; D014655:Vascular Resistance