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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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Analysis of left ventricular dimensions in operated pigs by echocardiography.Representative apical long-axis views of the four chambers in the pig heart by two-dimensional echocardiography – (i) before surgery, (ii) immediately after surgery, (iii) one week after surgery, (iv) two weeks after surgery, (v) four weeks after surgery and (vi) eight weeks after surgery. *, left atrial; ▿, left ventricular.
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pone-0111689-g004: Analysis of left ventricular dimensions in operated pigs by echocardiography.Representative apical long-axis views of the four chambers in the pig heart by two-dimensional echocardiography – (i) before surgery, (ii) immediately after surgery, (iii) one week after surgery, (iv) two weeks after surgery, (v) four weeks after surgery and (vi) eight weeks after surgery. *, left atrial; ▿, left ventricular.

Mentions: Color Doppler flow imaging was used to detect eccentric “drop-like” jets of mitral valve regurgitation near the left atrial wall in all pigs. The abnormal movement of the mitral muscle could also be detected. We showed that the mitral ring gradually expanded in pig hearts with increasing left ventricular (systolic and diastolic) and atrial volumes (Figure 3A). All of the above changes were indicative of a regurgitation jet that was caused by ischemic mitral regurgitation. Assessment of the regurgitation area (RA), left atrial area (LAA), regurgitation volume (RV) and regurgitation fraction (RF) was obtained using previously established methods [20], [21]. RA and RA/LAA were increased by 30% from baseline, at time points one, two, four, and eight weeks post-surgery (Table 1). The RV was 0.5 ml greater post-surgery, while RF ranged from 30% to 60% and the regurgitation jet velocity was greater than 300 cm/s at all of the observed time points post-surgery. These characteristics were indicative of moderate to severe mitral regurgitation. The RV was also significantly increased at two weeks post-surgery, which related to the gradual closing of the ameroid ring and posterior papillary muscle ischemia. The slight decrease in RA/LAA at two weeks post-surgery could be due to the gradual increase in atrial pressure and area. One week post-surgery, the LVEDV and LVESV were not significantly different from baseline, while the LAESV and LAEDV had significantly increased over baseline values (Table 2). However, four weeks post-surgery, the LVEDV, LVDSV, LAEDV and LAESV were all significantly increased when compared to baseline values, indicating significant left ventricular remodeling. Eight weeks post-surgery, changes to the LAEDV and LAESV were even greater than those of LVEDV and LVESV in pig hearts. In fact, LAEDV and LAESV were found to be three times higher than baseline (Figure 4).


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)

Analysis of left ventricular dimensions in operated pigs by echocardiography.Representative apical long-axis views of the four chambers in the pig heart by two-dimensional echocardiography – (i) before surgery, (ii) immediately after surgery, (iii) one week after surgery, (iv) two weeks after surgery, (v) four weeks after surgery and (vi) eight weeks after surgery. *, left atrial; ▿, left ventricular.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0111689-g004: Analysis of left ventricular dimensions in operated pigs by echocardiography.Representative apical long-axis views of the four chambers in the pig heart by two-dimensional echocardiography – (i) before surgery, (ii) immediately after surgery, (iii) one week after surgery, (iv) two weeks after surgery, (v) four weeks after surgery and (vi) eight weeks after surgery. *, left atrial; ▿, left ventricular.
Mentions: Color Doppler flow imaging was used to detect eccentric “drop-like” jets of mitral valve regurgitation near the left atrial wall in all pigs. The abnormal movement of the mitral muscle could also be detected. We showed that the mitral ring gradually expanded in pig hearts with increasing left ventricular (systolic and diastolic) and atrial volumes (Figure 3A). All of the above changes were indicative of a regurgitation jet that was caused by ischemic mitral regurgitation. Assessment of the regurgitation area (RA), left atrial area (LAA), regurgitation volume (RV) and regurgitation fraction (RF) was obtained using previously established methods [20], [21]. RA and RA/LAA were increased by 30% from baseline, at time points one, two, four, and eight weeks post-surgery (Table 1). The RV was 0.5 ml greater post-surgery, while RF ranged from 30% to 60% and the regurgitation jet velocity was greater than 300 cm/s at all of the observed time points post-surgery. These characteristics were indicative of moderate to severe mitral regurgitation. The RV was also significantly increased at two weeks post-surgery, which related to the gradual closing of the ameroid ring and posterior papillary muscle ischemia. The slight decrease in RA/LAA at two weeks post-surgery could be due to the gradual increase in atrial pressure and area. One week post-surgery, the LVEDV and LVESV were not significantly different from baseline, while the LAESV and LAEDV had significantly increased over baseline values (Table 2). However, four weeks post-surgery, the LVEDV, LVDSV, LAEDV and LAESV were all significantly increased when compared to baseline values, indicating significant left ventricular remodeling. Eight weeks post-surgery, changes to the LAEDV and LAESV were even greater than those of LVEDV and LVESV in pig hearts. In fact, LAEDV and LAESV were found to be three times higher than baseline (Figure 4).

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