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Combination proximal pulmonary artery coiling and distal embolization induces chronic elevations in pulmonary artery pressure in Swine.

Aguero J, Ishikawa K, Fish KM, Hammoudi N, Hadri L, Garcia-Alvarez A, Ibanez B, Fuster V, Hajjar RJ, Leopold JA - PLoS ONE (2015)

Bottom Line: In this study, we present a novel swine model that develops cardiopulmonary hemodynamics and structural changes characteristic of chronic PH.At 8 weeks after the index procedure, combined embolization procedure animals had increased mean pulmonary artery pressure (mPA) and pulmonary vascular resistance (PVR) compared to the controls with no effect on left heart or systemic pressures.RV remodeling and RV dysfunction were also present with a decrease in the RV ejection fraction, increase in the myocardial performance index, impaired longitudinal function, as well as cardiomyocyte hypertrophy, and interstitial fibrosis, which were not present in the controls.

View Article: PubMed Central - PubMed

Affiliation: Cardiovascular Research Center, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America; Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC)- Epidemiology, Atherothrombosis and Imaging Department, Madrid, Spain.

ABSTRACT
Pulmonary hypertension (PH) is associated with aberrant vascular remodeling and right ventricular (RV) dysfunction that contribute to early mortality. Large animal models that recapitulate human PH are essential for mechanistic studies and evaluating novel therapies; however, these models are not readily accessible to the field owing to the need for advanced surgical techniques or hypoxia. In this study, we present a novel swine model that develops cardiopulmonary hemodynamics and structural changes characteristic of chronic PH. This percutaneous model was created in swine (n=6) by combining distal embolization of dextran beads with selective coiling of the lobar pulmonary arteries (2 procedures per lung over 4 weeks). As controls, findings from this model were compared with those from a standard weekly distal embolization model (n=6) and sham animals (n=4). Survival with the combined embolization model was 100%. At 8 weeks after the index procedure, combined embolization procedure animals had increased mean pulmonary artery pressure (mPA) and pulmonary vascular resistance (PVR) compared to the controls with no effect on left heart or systemic pressures. RV remodeling and RV dysfunction were also present with a decrease in the RV ejection fraction, increase in the myocardial performance index, impaired longitudinal function, as well as cardiomyocyte hypertrophy, and interstitial fibrosis, which were not present in the controls. Pulmonary vascular remodeling occurred in both embolization models, although only the combination embolization model had a decrease in pulmonary capacitance. Taken together, these cardiopulmonary hemodynamic and structural findings identify the novel combination embolization swine model as a valuable tool for future studies of chronic PH.

No MeSH data available.


Related in: MedlinePlus

Right ventricular fibrosis and hypertrophy.Myocardial fibrosis was examined in RV sections from the P+D-Embo group (n = 6), D-Embo group (n = 6) and sham controls (n = 4) stained with Masson’s trichrome and quantified as % area fibrosis (top). Cardiomyocyte hypertrophy was evaluated by staining RV sections with wheat germ agglutinin and co-staining with phalloidin to assess cardiomyocyte cross-sectional area (bottom). Representative images are shown for each group. P+D-Embo, proximal and distal embolization group; D-Embo, distal embolization group; RV, right ventricular. *p<0.05 vs. sham, D-Embo by ANOVA.
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pone.0124526.g005: Right ventricular fibrosis and hypertrophy.Myocardial fibrosis was examined in RV sections from the P+D-Embo group (n = 6), D-Embo group (n = 6) and sham controls (n = 4) stained with Masson’s trichrome and quantified as % area fibrosis (top). Cardiomyocyte hypertrophy was evaluated by staining RV sections with wheat germ agglutinin and co-staining with phalloidin to assess cardiomyocyte cross-sectional area (bottom). Representative images are shown for each group. P+D-Embo, proximal and distal embolization group; D-Embo, distal embolization group; RV, right ventricular. *p<0.05 vs. sham, D-Embo by ANOVA.

Mentions: There was also evidence of RV structural remodeling in P+D-Embo pigs. Compared to shams and D-Embo animals, the RV end-systolic volume index and end-diastolic index was increased significantly in P+D-Embo pigs. There was an increase in RV weight in P+D-Embo pigs (1.14 ± 0.07 vs. 1.18 ± 0.09 vs. 1.42 ± 0.26 gm/kg, p<0.05) and RV/LV + septum weight (0.40 ± 0.03 vs. 0.41 ± 0.02 vs. 0.47 ± 0.6 gm/kg, p<0.05) indicating that RV hypertrophic remodeling had occurred. To further characterize RV remodeling, myocardial interstitial fibrosis and cardiomyocyte hypertrophy were examined. Compared to sham and D-Embo animals, there was a significant increase in RV interstitial fibrosis in the P+D-Embo pigs (Fig 5). At a cellular level, there was evidence of RV cardiomyocyte remodeling with an increase in cardiomyocyte cross-sectional area observed only in in the P+D-Embo animals (Fig 5).


Combination proximal pulmonary artery coiling and distal embolization induces chronic elevations in pulmonary artery pressure in Swine.

Aguero J, Ishikawa K, Fish KM, Hammoudi N, Hadri L, Garcia-Alvarez A, Ibanez B, Fuster V, Hajjar RJ, Leopold JA - PLoS ONE (2015)

Right ventricular fibrosis and hypertrophy.Myocardial fibrosis was examined in RV sections from the P+D-Embo group (n = 6), D-Embo group (n = 6) and sham controls (n = 4) stained with Masson’s trichrome and quantified as % area fibrosis (top). Cardiomyocyte hypertrophy was evaluated by staining RV sections with wheat germ agglutinin and co-staining with phalloidin to assess cardiomyocyte cross-sectional area (bottom). Representative images are shown for each group. P+D-Embo, proximal and distal embolization group; D-Embo, distal embolization group; RV, right ventricular. *p<0.05 vs. sham, D-Embo by ANOVA.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4414513&req=5

pone.0124526.g005: Right ventricular fibrosis and hypertrophy.Myocardial fibrosis was examined in RV sections from the P+D-Embo group (n = 6), D-Embo group (n = 6) and sham controls (n = 4) stained with Masson’s trichrome and quantified as % area fibrosis (top). Cardiomyocyte hypertrophy was evaluated by staining RV sections with wheat germ agglutinin and co-staining with phalloidin to assess cardiomyocyte cross-sectional area (bottom). Representative images are shown for each group. P+D-Embo, proximal and distal embolization group; D-Embo, distal embolization group; RV, right ventricular. *p<0.05 vs. sham, D-Embo by ANOVA.
Mentions: There was also evidence of RV structural remodeling in P+D-Embo pigs. Compared to shams and D-Embo animals, the RV end-systolic volume index and end-diastolic index was increased significantly in P+D-Embo pigs. There was an increase in RV weight in P+D-Embo pigs (1.14 ± 0.07 vs. 1.18 ± 0.09 vs. 1.42 ± 0.26 gm/kg, p<0.05) and RV/LV + septum weight (0.40 ± 0.03 vs. 0.41 ± 0.02 vs. 0.47 ± 0.6 gm/kg, p<0.05) indicating that RV hypertrophic remodeling had occurred. To further characterize RV remodeling, myocardial interstitial fibrosis and cardiomyocyte hypertrophy were examined. Compared to sham and D-Embo animals, there was a significant increase in RV interstitial fibrosis in the P+D-Embo pigs (Fig 5). At a cellular level, there was evidence of RV cardiomyocyte remodeling with an increase in cardiomyocyte cross-sectional area observed only in in the P+D-Embo animals (Fig 5).

Bottom Line: In this study, we present a novel swine model that develops cardiopulmonary hemodynamics and structural changes characteristic of chronic PH.At 8 weeks after the index procedure, combined embolization procedure animals had increased mean pulmonary artery pressure (mPA) and pulmonary vascular resistance (PVR) compared to the controls with no effect on left heart or systemic pressures.RV remodeling and RV dysfunction were also present with a decrease in the RV ejection fraction, increase in the myocardial performance index, impaired longitudinal function, as well as cardiomyocyte hypertrophy, and interstitial fibrosis, which were not present in the controls.

View Article: PubMed Central - PubMed

Affiliation: Cardiovascular Research Center, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America; Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC)- Epidemiology, Atherothrombosis and Imaging Department, Madrid, Spain.

ABSTRACT
Pulmonary hypertension (PH) is associated with aberrant vascular remodeling and right ventricular (RV) dysfunction that contribute to early mortality. Large animal models that recapitulate human PH are essential for mechanistic studies and evaluating novel therapies; however, these models are not readily accessible to the field owing to the need for advanced surgical techniques or hypoxia. In this study, we present a novel swine model that develops cardiopulmonary hemodynamics and structural changes characteristic of chronic PH. This percutaneous model was created in swine (n=6) by combining distal embolization of dextran beads with selective coiling of the lobar pulmonary arteries (2 procedures per lung over 4 weeks). As controls, findings from this model were compared with those from a standard weekly distal embolization model (n=6) and sham animals (n=4). Survival with the combined embolization model was 100%. At 8 weeks after the index procedure, combined embolization procedure animals had increased mean pulmonary artery pressure (mPA) and pulmonary vascular resistance (PVR) compared to the controls with no effect on left heart or systemic pressures. RV remodeling and RV dysfunction were also present with a decrease in the RV ejection fraction, increase in the myocardial performance index, impaired longitudinal function, as well as cardiomyocyte hypertrophy, and interstitial fibrosis, which were not present in the controls. Pulmonary vascular remodeling occurred in both embolization models, although only the combination embolization model had a decrease in pulmonary capacitance. Taken together, these cardiopulmonary hemodynamic and structural findings identify the novel combination embolization swine model as a valuable tool for future studies of chronic PH.

No MeSH data available.


Related in: MedlinePlus