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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

Temporal changes in mPA pressure and PVR index.The change over time in mPA pressure (top) and PVR index (bottom) measured at each embolization procedure and at the 8 week follow-up examination was evaluated in the P+D-Embo group (n = 6), D-Embo group (n = 6) and sham controls (n = 4). mPA, mean pulmonary artery; PVR, pulmonary vascular resistance; P+D-Embo, proximal and distal embolization group; D-Embo, distal embolization group. Data are reported as mean ± SD, *p<0.05 vs. sham, D-Embo by ANOVA.
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pone.0124526.g004: Temporal changes in mPA pressure and PVR index.The change over time in mPA pressure (top) and PVR index (bottom) measured at each embolization procedure and at the 8 week follow-up examination was evaluated in the P+D-Embo group (n = 6), D-Embo group (n = 6) and sham controls (n = 4). mPA, mean pulmonary artery; PVR, pulmonary vascular resistance; P+D-Embo, proximal and distal embolization group; D-Embo, distal embolization group. Data are reported as mean ± SD, *p<0.05 vs. sham, D-Embo by ANOVA.

Mentions: The time course of the rise in mPA pressure and PVR index was also examined in both models (Fig 4). In D-Embo pigs, the peak mPA pressure measured was 21 ± 4 mmHg and was recorded at week 5, one week before the last embolization procedure; however, this increase in pressure was normalized at the 8 week follow-up examination and was similar to pressures recorded in sham controls. In contrast, in P+D-Embo pigs, mPA pressures increased by week 2, reached a maximum of 29 ± 8 mmHg (2.1-fold increase over baseline) by week 3, with some evidence of recovery to 23 ± 4 mmHg mmHg by week 8 (1.6-fold increase over baseline). The PVR index followed a similar temporal course with no difference observed between D-Embo animals and sham controls compared to their respective baseline measurements. In P+D-Embo pigs, the PVR index increased to 5.1 ± 1.1 WU*m2 at week 3 and by week 8 remained increased 82% over baseline, similar to the temporal trend observed for mPA pressures. These hemodynamic changes occurred without any observed differences between the groups with respect to the cardiac index or mean aortic pressure, both of which were preserved over time.


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)

Temporal changes in mPA pressure and PVR index.The change over time in mPA pressure (top) and PVR index (bottom) measured at each embolization procedure and at the 8 week follow-up examination was evaluated in the P+D-Embo group (n = 6), D-Embo group (n = 6) and sham controls (n = 4). mPA, mean pulmonary artery; PVR, pulmonary vascular resistance; P+D-Embo, proximal and distal embolization group; D-Embo, distal embolization group. Data are reported as mean ± SD, *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.g004: Temporal changes in mPA pressure and PVR index.The change over time in mPA pressure (top) and PVR index (bottom) measured at each embolization procedure and at the 8 week follow-up examination was evaluated in the P+D-Embo group (n = 6), D-Embo group (n = 6) and sham controls (n = 4). mPA, mean pulmonary artery; PVR, pulmonary vascular resistance; P+D-Embo, proximal and distal embolization group; D-Embo, distal embolization group. Data are reported as mean ± SD, *p<0.05 vs. sham, D-Embo by ANOVA.
Mentions: The time course of the rise in mPA pressure and PVR index was also examined in both models (Fig 4). In D-Embo pigs, the peak mPA pressure measured was 21 ± 4 mmHg and was recorded at week 5, one week before the last embolization procedure; however, this increase in pressure was normalized at the 8 week follow-up examination and was similar to pressures recorded in sham controls. In contrast, in P+D-Embo pigs, mPA pressures increased by week 2, reached a maximum of 29 ± 8 mmHg (2.1-fold increase over baseline) by week 3, with some evidence of recovery to 23 ± 4 mmHg mmHg by week 8 (1.6-fold increase over baseline). The PVR index followed a similar temporal course with no difference observed between D-Embo animals and sham controls compared to their respective baseline measurements. In P+D-Embo pigs, the PVR index increased to 5.1 ± 1.1 WU*m2 at week 3 and by week 8 remained increased 82% over baseline, similar to the temporal trend observed for mPA pressures. These hemodynamic changes occurred without any observed differences between the groups with respect to the cardiac index or mean aortic pressure, both of which were preserved over time.

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