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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

View larger version (10K): [in a new window]   Figure 1 Summary of the experimental protocol. The horizontal line denotes the time in weeks after surgery. At time = 0, after BS measurements, surgery was performed. Function was followed on a weekly basis. At sacrifice (8 or 12 weeks) tissue samples were taken for histology, beta-adrenergic receptor study, determination of the tissue high energy phosphate content and determination of regional perfusion. BS = baseline, RF = resting flow, CR = coronary reserve, angio = coronary angiography, Dob echo = dobutamine echocardiography, WT = wall thickening measurement using weekly two-dimensional echocardiography.

View larger version (19K): [in a new window]   Figure 2 Weekly variation of regional function for two dogs (± PTCA), with panel A showing individual anterior wall data and panel B showing data from the collateral dependent region. Note the weekly variation in function or the episodic nature of dysfunction for both regions.

View larger version (24K): [in a new window]   Figure 3 Panel A: Wall thickening (%) data (mean ± SD) from A, IP and MS regions as a function of time for the non-PTCA group. Midseptum, however, had normal function throughout the entire follow-up period. Panel B: Wall thickening (%) data (mean ± SD) from A, IP and MS regions as a function of time for the PTCA group with a follow-up period of 12 weeks. After PTCA there is significant improvement in the A wall. A = anterior; IP = inferoposterior; MS = midseptum; PTCA = percutaneous transluminal coronary angioplasty.

View larger version (23K): [in a new window]   Figure 4 Perfusion-function relationship at eight weeks and 12 weeks after surgery for anterior and collateral dependent wall. The data are expressed as a ratio of measurements at sacrifice versus baseline. CR = coronary reserve; RF = resting flow; WT = % wall thickening.

View larger version (154K): [in a new window]   Figure 5 Top Panel: Light microscopy from collateral dependent region (inferoposterior) showing normal structure. Magnification: x 832, reduced by 60%; Bottom Panel: Electron microscopy showing a myocyte with the typical perinuclear loss of myofilaments, mitochondria with altered shape and the granular material around the nucleus which represents glycogen. These morphological changes have been described in patients.

View larger version (118K): [in a new window]   Figure 6 Top Panel: Coronary angiography performed at four weeks postsurgery confirmed the presence of tight stenosis on the LAD, and shows retrograde filling of the circumflex. Ameroid constrictors (placed around the circumflex and right coronary artery) appear as radio opaque rings. Bottom Panel: Percutaneous transluminal coronary angioplasty of the LAD was performed at eight weeks after surgery. LAD = left anterior descending artery.