4.7 Article

Experimental Pig Model of Old Myocardial Infarction with Long Survival Leading to Chronic Left Ventricular Dysfunction and Remodeling as Evaluated by PET

Journal

JOURNAL OF NUCLEAR MEDICINE
Volume 52, Issue 5, Pages 761-768

Publisher

SOC NUCLEAR MEDICINE INC
DOI: 10.2967/jnumed.110.084848

Keywords

experimental model; PET; myocardial flow reserve; remodeling; regeneration therapy

Funding

  1. New Energy and Industrial Technology Development Organization (NEDO), Japan
  2. Ministry of Health, Labor and Welfare (MHLW), Japan

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A pig model of reduced left ventricular (LV) function and remodeling or chronic heart failure with long survival after myocardial infarction (MI) has not been established. The aim of this study was to evaluate the pathophysiologic status of a pig model of old MI using a series of PET studies. Methods: Twenty-seven male farm pigs were divided into 2 groups: 7 animals in the control group and 20 animals that underwent a proximal coronary artery (CA) occlusion using an ameroid constrictor after distal CA ligation. A series of PET examinations was performed to assess LV volumes, LV functions, myocardial perfusion response to adenosine, and viability as water-perfusable tissue index. Results: The distal CA ligation inhibited arrhythmia during and after the operation, and a transmural anteroseptal MI, with an infarction area of 27% +/- 5% of the whole left ventricle, was generated with a survival rate of 75% at 4 mo. Wall motion evaluated by (18)F-FDG PET was diffusely reduced, including the noninfarcted wall. Global LV ejection fraction as assessed by gated C(15)O PET was reduced (39% +/- 16%) in the group undergoing occlusion, compared with the control group (66% +/- 16%, P < 0.05). LV end-systolic (31.4 +/- 9.2 cm(3)) and end-diastolic (52.7 +/- 10.2 cm(3)) volumes were increased, compared with controls (15.2 +/- 9.4 cm(3), P < 0.01, and 41.7 +/- 11.5 cm(3), P < 0.05, respectively). Histology showed hypertrophy and development of microscopic fibrosis in noninfarcted myocardium. PET demonstrated the reduced myocardial perfusion response to adenosine and also reduced water-perfusable tissue index in remote segments. Conclusion: The pig model of old MI generated by the chronic proximal CA obstruction after distal ligation was characterized by LV dysfunction and remodeling, with a high survival rate.

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