A pig model of ischemic mitral regurgitation induced by mitral chordae tendinae rupture and implantation of an ameroid constrictor

PLoS One. 2014 Dec 5;9(12):e111689. doi: 10.1371/journal.pone.0111689. eCollection 2014.

Abstract

A miniature pig model of ischemic mitral regurgitation (IMR) was developed by posterior mitral chordae tendinae rupture and implantation of an ameroid constrictor. A 2.5-mm ameroid constrictor was placed around the left circumflex coronary artery (LCX) of male Tibetan miniature pigs to induce ischemia, while the posterior mitral chordae tendinae was also ruptured. X-ray coronary angiography, ECG analysis, echocardiography, and magnetic resonance imaging (MRI) were used to evaluate heart structure and function in pigs at baseline and one, two, four and eight weeks after the operation. Blood velocity of the mitral regurgitation was found to be between medium and high levels. Angiographic analyses revealed that the LCX closure was 10-20% at one week, 30-40% at two weeks and 90-100% at four weeks subsequent ameroid constrictor implantation. ECG analysis highlighted an increase in the diameter of the left atria (LA) at two weeks post-operation as well as ischemic changes in the left ventricle (LV) and LA wall at four weeks post-operation. Echocardiography and MRI further detected a gradual increase in LA and LV volumes from two weeks post-operation. LV end diastolic and systolic volumes as well as LA end diastolic and systolic volume were also significantly higher in pig hearts post-operation when compared to baseline. Pathological changes were observed in the heart, which included scar tissue in the ischemic central area of the LV. Transmission electron microscopy highlighted the presence of contraction bands and edema surrounding the ischemia area, including inflammatory cell infiltration within the ischemic area. We have developed a pig model of IMR using the posterior mitral chordae tendineae rupture technique and implantation of an ameroid constrictor. The pathological features of this pig IMR model were found to mimic the natural history and progression of IMR in patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Caseins / therapeutic use
  • Coronary Vessels / physiopathology*
  • Disease Models, Animal
  • Echocardiography
  • Heart Valve Diseases / blood
  • Heart Valve Diseases / physiopathology*
  • Heart Valve Diseases / therapy
  • Heart Ventricles / physiopathology
  • Humans
  • Hydrogels / therapeutic use
  • Magnetic Resonance Imaging
  • Mitral Valve / physiopathology
  • Mitral Valve Insufficiency / blood
  • Mitral Valve Insufficiency / physiopathology*
  • Myocardial Ischemia / physiopathology*
  • Sus scrofa
  • Swine
  • Swine, Miniature
  • Troponin / blood

Substances

  • Caseins
  • Hydrogels
  • Troponin
  • ameroid

Grants and funding

This work is sponsored by the Beijing Science and Technology Committee (Project No: Z101107052210004) and Natural Science Foundation of China (Project No: 81370190). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.