Repeated stunning precedes myocardial hibernation in progressive multiple coronary artery obstruction

OBJECTIVE The aim of this study was to characterize a regional myocardial f low-function relationship in collateral dependent myocardium produced by mu ltiple 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 pro ximal LAD (left anterior descending artery) (luminal stenosis +/-77%) in 18 dogs. Weekly two-dimensional echocardiography was performed for regional f unction (anterior [A], inferoposterior [IP], wall thickening [WT]), and fra ctional shortening (FS). Colored microspheres injected at baseline and befo re sacrifice, before and after dipyridamole (0.5 mg/kg) injection, determin ed resting flow (RF) and coronary reserve (CR), respectively. RESULTS Coronary angiography performed at four weeks after surgery confirme d 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 < 0.00 5 vs, baseline [BS]). With dobutamine a biphasic response (improvement in A and IP WT between 5-15 and dysfunction between 20-30 mu g/kg/min) was obse rved. Seven dogs were sacrificed at eight weeks and showed normal RF but re duced transmural CR (A: 75 +/- 18%; IF: 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 wee ks). 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 sh owed normal histological findings and high energy phosphate content in all dogs. Radioligand binding assays using I-125-iodocyanopindolol showed downr egulation of beta-adrenergic receptor density in the dysfunctional regions compared with control. CONCLUSIONS In this canine model of viable, collateral dependent and revers ibly dysfunctional myocardium, there was early episodic dysfunction followe d by persistent dysfunction which was initially associated with normal RF a nd later with subendocardial hypoperfusion. (C) 1999 by the American Colleg e of Cardiology.