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EXPERIMENTAL STUDIES

Repeated stunning precedes myocardial hibernation in progressive multiple coronary artery obstruction

Bharati Shivalkar, MD^{* d}, Willem Flameng, MD ⁴, Monika Szilard, MD^{* 4}, Sorin Pislaru, MD^{* 4}, Marcel Borgers, PhD ⁴ and Johan Vanhaecke, MD^{* 4}

^* Department of Cardiology and Cardiac Surgery, Laboratory of Experimental Cardiology, Katholieke Universiteit Leuven, Leuven, Belgium
Department of Cardiology and Cardiac Surgery, Laboratory of Experimental Cardiac Surgery and Anesthesiology, Katholieke Universiteit Leuven, Leuven, Belgium
Janssen Research Foundation, Beerse, Belgium
^d University of Maastricht, Maastricht, the Netherlands

Manuscript received February 4, 1999; revised manuscript received June 29, 1999, accepted September 1, 1999.

Reprint requests and correspondence: Dr. Bharati Shivalkar, Department of Cardiology, University Hospital Gasthuisberg, KU Leuven, Herestraat 49, B-3000 Leuven, Belgium
bharati.shivalkar{at}skynet.be

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 µg/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.

Abbreviations and Acronyms   A = anterior   AR = adrenergic receptors   AS = anteroseptum   AW = anterior wall   Bmax = maximum number of binding sites   BS = baseline   CM = colored microspheres   CR = coronary reserve   ECG = electrocardiogram   endo = endocardial   epi = epicardial   FS = fractional shortening   HEPC = high energy phosphate content   HPLC = high performance liquid chromatography   i.m. = intramuscularly   IP = inferoposterior   IV = intravenous   Kd = dissociation constant   IW = inferior wall   LAD = left anterior descending artery   LV = left ventricle   MS = midseptum   PTCA = percutaneous transluminal coronary angioplasty   PW = posterior wall   QCA = quantitative coronary analysis   WT = wall thickening

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