Synopsis

Keywords: Myocardium, MR Value

This preclinical study has established that chronic coronary artery stenosis can induce significant myocyte loss with modest global replacement fibrosis that leads to global LV dysfunction and varying degrees of congestive heart failure.

Background: A large animal model of chronic coronary artery disease (CAD) is crucial for the understanding the underlying pathophysiological processes of chronic CAD and consequences for cardiac structure and function. The goal of this study was to develop a chronic model of ischemic cardiomyopathy in a swine model and to evaluate the changes of myocardial structure, myocardial motility, and myocardial viability during coronary stenosis. Methods: A total of 30 swine (including 24 experimental animals and 6 controls) were enrolled. The chronic ischemia model was constructed by using Ameroid constrictor in experimental group. The 24 experimental animals were further divided into 4 groups (6 animals in each group) and were sacrificed at 1, 2, 3 and 4 weeks after operation for pathological examination, respectively. Cardiac magnetic resonance (CMR) was performed preoperatively and weekly postoperatively until sacrificed. CMR cine images, rest/adenosine triphosphate (ATP) stress myocardial contrast perfusion and LGE were performed and analyzed. The rest wall thickening (WT) score was calculated from rest cine images. The MPRI (myocardial perfusion reserve index) and MPR (myocardial perfusion reserve) were calculated based on rest and stress perfusion images. Pathology staining including triphenyltetrazolium chloride, HE and picrosirus red staining were performed after swine were sacrificed. The time to formation of ischemic, hibernating, and infarcted myocardium was recorded. Results: In experimental group, from 1 week to 4 weeks after surgery, the rest WT score decreased gradually from 35.2±2.0%, 32.0±2.9% to 30.5±3.0% and finally 29.06±1.78%, p<0.001. Left ventricular ejection fraction was also impaired during modeling (58.9±12.6, 56.3±10.1,55.3±9.0,53.8±9.9, respectively). And the MPR and MPRI also tended to be lower throughout the study (MPRI dropped from 2.1±0.4, 2.0±0.2 to 1.8±0.3 and finally 1.7±0.1, p=0.004; MPR dropped from 2.3±0.4, 2.1±0.2 to 1.9±0.4 and finally 1.8±0.1, p<0.001). The ischemic myocardium was first appeared in the first week after surgery (ten segments), hibernated myocardium was first appeared in the second week after surgery (seventeen segments). LGE was first appeared in eight swine in the third weeks after surgery (16 segments). At 4w after surgery, average 9.6g scar tissue was found among 6 swine. At the same time, histological analysis established the presence of fibrosis and ongoing apoptosis in the infarcted area. Conclusion: Combing myocardial motion and stress perfusion have the capability to accurately identify the progress of chronic myocardial ischemia.

Acknowledgements

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References

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