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

Cui YC, Li K, Tian Y, Yuan WM, Peng P, Yang JZ, Zhang BJ, Zhang HD, Wu AL, Tang Y - PLoS ONE (2014)

Bottom Line: Blood velocity of the mitral regurgitation was found to be between medium and high levels.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.The pathological features of this pig IMR model were found to mimic the natural history and progression of IMR in patients.

View Article: PubMed Central - PubMed

Affiliation: State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Beijing Municipal Key Laboratory for Pre-clinical Evaluation of Cardiovascular Implantation Devices, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100037, People's Republic of China.

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.

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Histopathological analyses of the myocardium in operated pigs.A: H&E analysis of heart sections from operated pigs revealed compensatory thickening of the left ventricle and myocyte disarray. B: Masson trichrome stain of heart sections from operated pigs revealed left atrial fibrosis. Note the significant endocardial fibrosis. C&D: Transmission electron microscopy analysis revealed contraction bands and edema surrounding the ischemic area as well as inflammatory cell infiltration (8000×).
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pone-0111689-g006: Histopathological analyses of the myocardium in operated pigs.A: H&E analysis of heart sections from operated pigs revealed compensatory thickening of the left ventricle and myocyte disarray. B: Masson trichrome stain of heart sections from operated pigs revealed left atrial fibrosis. Note the significant endocardial fibrosis. C&D: Transmission electron microscopy analysis revealed contraction bands and edema surrounding the ischemic area as well as inflammatory cell infiltration (8000×).

Mentions: Analyses of pig heart structure post-surgery revealed that the pig hearts displayed chordae tendinae rupture (Grade I or Grade II) of the mitral valve and “jet lesions”, which have been previously described in the left ventricle [22], [23] and could be macroscopically observed in all cases. All of the hearts had undergone significant expansion and increased cardiac sphericity (Figure 6A). H&E and Masson trichrome stain analyses revealed that chronic ischemia and mitral regurgitation caused the cardiac pathological changes, including eccentric ventricular hypertrophy (Figure 6B), fibrosis of the left atrium (Figure 6) and scarring within the ischemic central area of the left ventricle. Transmission electron microscopy further demonstrated the appearance of contraction bands, edema surrounding the ischemic area and inflammatory cell infiltration within the ischemic area. Interestingly, there remained regions of heart muscle that contained an intact nucleus and uniform cytoplasmic staining. Proliferative changes were also retained within the normal (spared) tissue areas (Figure 6C). N-BT staining further revealed that the myocardial infarct area accounted for 7.6±1.8% of the total volume of the ventricle.


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

Cui YC, Li K, Tian Y, Yuan WM, Peng P, Yang JZ, Zhang BJ, Zhang HD, Wu AL, Tang Y - PLoS ONE (2014)

Histopathological analyses of the myocardium in operated pigs.A: H&E analysis of heart sections from operated pigs revealed compensatory thickening of the left ventricle and myocyte disarray. B: Masson trichrome stain of heart sections from operated pigs revealed left atrial fibrosis. Note the significant endocardial fibrosis. C&D: Transmission electron microscopy analysis revealed contraction bands and edema surrounding the ischemic area as well as inflammatory cell infiltration (8000×).
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4257529&req=5

pone-0111689-g006: Histopathological analyses of the myocardium in operated pigs.A: H&E analysis of heart sections from operated pigs revealed compensatory thickening of the left ventricle and myocyte disarray. B: Masson trichrome stain of heart sections from operated pigs revealed left atrial fibrosis. Note the significant endocardial fibrosis. C&D: Transmission electron microscopy analysis revealed contraction bands and edema surrounding the ischemic area as well as inflammatory cell infiltration (8000×).
Mentions: Analyses of pig heart structure post-surgery revealed that the pig hearts displayed chordae tendinae rupture (Grade I or Grade II) of the mitral valve and “jet lesions”, which have been previously described in the left ventricle [22], [23] and could be macroscopically observed in all cases. All of the hearts had undergone significant expansion and increased cardiac sphericity (Figure 6A). H&E and Masson trichrome stain analyses revealed that chronic ischemia and mitral regurgitation caused the cardiac pathological changes, including eccentric ventricular hypertrophy (Figure 6B), fibrosis of the left atrium (Figure 6) and scarring within the ischemic central area of the left ventricle. Transmission electron microscopy further demonstrated the appearance of contraction bands, edema surrounding the ischemic area and inflammatory cell infiltration within the ischemic area. Interestingly, there remained regions of heart muscle that contained an intact nucleus and uniform cytoplasmic staining. Proliferative changes were also retained within the normal (spared) tissue areas (Figure 6C). N-BT staining further revealed that the myocardial infarct area accounted for 7.6±1.8% of the total volume of the ventricle.

Bottom Line: Blood velocity of the mitral regurgitation was found to be between medium and high levels.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.The pathological features of this pig IMR model were found to mimic the natural history and progression of IMR in patients.

View Article: PubMed Central - PubMed

Affiliation: State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Beijing Municipal Key Laboratory for Pre-clinical Evaluation of Cardiovascular Implantation Devices, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100037, People's Republic of China.

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.

Show MeSH
Related in: MedlinePlus