Acute ischemic dysfunction alters coronary flow reserve in remote nonischemic regions: Potential mechanical etiology identified in an acute canine model

Background. Impaired coronary flow reserve (CFR) has been observed in remot e nonischemic regions in patients after myocardial infarction, The mechanis m for this impairment in remote nonischemic CFR remains undefined, This stu dy evaluates the effect of progressive regional ischemic dysfunction on fun ction in remote nonischemic regions, and the effect of the extent of dysfun ction on remote nonischemic coronary flow and CFR, Methods. In an anesthetized open-chest canine model (n = 7) of acute progre ssive distal and proximal left anterior descending (LAD) coronary artery oc clusion, regional myocardial thickening fraction and coronary flow and CPR were measured with Doppler probes. CFR was assessed by an intracoronary inj ection of 36 mu g of adenosine, Changes in thickening fraction and CFR were evaluated for isovolumic, ejection, and diastolic phases, Changes in resti ng regional flow were also assessed using radiolabeled microspheres, The ex tent of the ischemic area was defined as regions of myocardium with endocar dial 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 baselin e (18% +/- 1%) to distal (-8% +/- 1%,) and proximal (-4% a 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 i n the remote nonischemic left circumflex (LCX) artery region (baseline 12% +/- 1%; distal occlusion 15% +/- 2%, P = .014 vs baseline; proximal occlusi on 17% +/- 2%, P = .02 vs baseline). Most of the increase in remote thicken ing fraction occurred during the isovolumic phase. There was no significant change in resting flow in remote nonischemic LCX regions or global hemodyn amic parameters. However, there was a progressive decrease in remote nonisc hemic CFR (baseline 2.44 +/- 0.3), distal occlusion (2.19 +/- 0.31; P = .05 5 vs baseline), and proximal occlusion (1.79 +/- 0.22; P = 0.004 vs baselin e, and P = .012 vs distal occlusion), A progressive decrease in CFR was not ed in each phase of the cardiac cycle. Conclusion. In a canine model of acute progressive distal and proximal coro nary occlusion, we observed a progressive decrease in CFR in remote nonisch emic regions concurrent with an increase in the extent of ischemia, The dec rease in remote nonischemic CFR was associated with ischemia-induced isovol umic bulging, which placed the remote regions at a mechanical disadvantage. These observations suggest a potential mechanical etiology for the observe d impairment in remote CFR, Alterations in remote nonischemic CFR during ac ute ischemia may have important clinical implications for perfusion scintig raphy.