An experimental animal model of chronic myocardial hibernation: comparative study of cine-MR, myocardial single photon emission computed tomography and pathology

Objective: To establish the chronic low-flow myocardial hibernation animal model in pigs, and to assess the diagnostic value for myocardial hibernation by using various imaging methods. Methods: A total of 13 miniswine (30-40 kg) were used. All animals underwent general anesthesia and orotracheal intubation while the animals were mechanically ventilated. Under sterile conditions, left ventriculography and coronary angiography were performed by introduction of catheter into the right femoral artery. Further, a left anterolateral thoracotomy was performed in the third intercostal space. The proximal LCX was dissected free to allow placement of an ameroid constrictor. More than 1 month later, left ventriculography and coronary angiography were performed again, followed by cine-MRI at rest and during stress with low-dose of dobutamine (5μg·kg-1·min-1), respectively. Traditional and/or breath-hold cine-MRI were used to evaluate regional left ventricular wall motion, corresponding to basal, midventricular and apical short-axis tomograms. Regional wall motion score index (WMSI) was calculated. At the same time 99mTc-MIBI myocardial SPECT was performed at rest and during nitroglycerin administration, respectively. All animals were finally sacrificed for pathological examination. Triphenyl tetrazolium chloride (TTC) staining was used to assess the myocardial infarction. Electron microscopy was used to identify myocardial cellular changes characteristic of hibernating myocardium. Results: Three pigs died during surgery or within two weeks after surgery. One pig died of anesthesia during SPECT examination, 1 pig suffered from aneurysm, and another one pig showed negative findings. The other 7 pigs were found with hypokinetic (n=4) or akinetic (n=3) myocardial regions related to stenosed LCX (70%-99%). Resting cine-MRI demonstrated decreased regional motion of the lateral and posteroinferior walls (ischemic regions) of the left ventricle (n=7), compared with the nonischemic anteroseptal regions; but the low dose dobutamine (5μg·kg-1·min-1) could recover those hypokinetic or akinetic myocardial regions, characteristic of hibernating myocardium. Resting 99mTc-MIBI myocardial SPECT (n=6) showed a fixed perfusion defect on the corresponding ischemic areas, which became reversible on the nitrate-augmented myocardial perfusion imaging. It also indicated myocardial viability presented at the ischemic areas. TTC staining revealed patchy infarction of the area-at-risk localized to the endocardial surface (n=3), and no myocardial infarction (n=4). Electron microscopy of sections from the hibernating regions revealed loss of contractile materials, increased numbers of small mitochondria, and glycogen accumulation within viable cardiomyocytes, which had been described as hallmarks of hibernating myocardium. Conclusion: Chronic low-flow myocardial hibernation can be reproduced in an animal model during progressive coronary stenosis caused by ameroid constrictor