title: Repeated stunning precedes myocardial hibernation in progressive multiple coronary artery obstruction.
abstract: OBJECTIVE
  The aim of this study was to characterize a regional myocardial flow-function relationship in collateral dependent myocardium produced by multiple coronary artery obstruction.
  
  
  METHODS
  Ameroid constrictors were placed around the proximal right (RC) and circumflex (CX) coronary arteries and a silicon tubing cuff around the proximal LAD (left anterior descending artery) (luminal stenosis +/- 77%) in 18 dogs. Weekly two-dimensional echocardiography was performed for regional function (anterior [A], inferoposterior [IP], wall thickening [WT]), and fractional shortening (FS). Colored microspheres injected at baseline and before sacrifice, before and after dipyridamole (0.5 mg/kg) injection, determined resting flow (RF) and coronary reserve (CR), respectively.
  
  
  RESULTS
  Coronary angiography performed at four weeks after surgery confirmed occlusion of RC and CX with collateralization and a tight stenosis of LAD. Initially, an episodic reduction in A and IP WT was observed which became persistent later (AWT: 16 +/- 3%; IPWT: 16 +/- 4%, FS: 20 +/- 4%, p < 0.005 vs. baseline [BS]). With dobutamine a biphasic response (improvement in A and IP WT between 5-15 and dysfunction between 20-30 microg/kg/min) was observed. Seven dogs were sacrificed at eight weeks and showed normal RF but reduced transmural CR (A: 75 +/- 18%; IP: 46 +/- 22% of control). Seven dogs underwent PTCA of the LAD at eight weeks and showed gradual improvement in AWT with normalization at 12 weeks (AWT: 30 +/- 5%, p < 0.001 vs. eight weeks). At sacrifice RF and CR in the A wall were normal but there was reduced subendocardial RF in the IP region (64% of BS). Further, biopsy samples showed normal histological findings and high energy phosphate content in all dogs. Radioligand binding assays using 125I-iodocyanopindolol showed downregulation of beta-adrenergic receptor density in the dysfunctional regions compared with control.
  
  
  CONCLUSIONS
  In this canine model of viable, collateral dependent and reversibly dysfunctional myocardium, there was early episodic dysfunction followed by persistent dysfunction which was initially associated with normal RF and later with subendocardial hypoperfusion.
authors.affiliation: Department of Cardiology and Cardiac Surgery, Katholieke Universiteit Leuven, Belgium. bharati.shivalkar@skynet.be
authors.forename: B
authors.initials: B
authors.lastname: Shivalkar
authors.forename: W
authors.initials: W
authors.lastname: Flameng
authors.forename: M
authors.initials: M
authors.lastname: Szilard
authors.forename: S
authors.initials: S
authors.lastname: Pislaru
authors.forename: M
authors.initials: M
authors.lastname: Borgers
authors.forename: J
authors.initials: J
authors.lastname: Vanhaecke
mesh_terms: D000818:Animals; D002316:Cardiotonic Agents / Q000008:administration & dosage; D003097:Collateral Circulation / Q000187:drug effects; D003326:Coronary Circulation / Q000187:drug effects; D003327:Coronary Disease / Q000150:complications* / Q000175:diagnosis / Q000503:physiopathology; D004195:Disease Models, Animal; D018450:Disease Progression; D004285:Dogs; D004452:Echocardiography; D005260:Female; D006352:Heart Ventricles / Q000473:pathology / Q000503:physiopathology; D007275:Injections, Intravenous; D019157:Ischemic Preconditioning, Myocardial; D008297:Male; D009204:Myocardial Revascularization / Q000379:methods; D017682:Myocardial Stunning / Q000175:diagnosis / Q000209:etiology* / Q000503:physiopathology; D011943:Receptors, Adrenergic, beta / Q000378:metabolism; D012039:Regional Blood Flow / Q000187:drug effects; D014665:Vasodilator Agents / Q000008:administration & dosage
chemical_list: D002316:Cardiotonic Agents; D011943:Receptors, Adrenergic, beta; D014665:Vasodilator Agents