Use of Mechanical Circulatory Support in a Large Animal Model of Pulmonary Hypertension During Exercise
Presented During: Welcome Reception and Poster Competition | Sponsored by: TransMedics
Vanderbilt University Hospital
Nashville, TN
United States - Contact Me
Victoria Simon completed her undergraduate training at Case Western Reserve University and medical school at the University of Cincinnati College of Medicine. She is a Cardiac Surgery Research Fellow in the Vanderbilt University Medical Center Laboratory for Organ Regeneration, Recovery, and Replacement.
Friday, September 20, 2024: 5:00 PM - 6:30 PM
Omni King Edward Hotel
Description
OBJECTIVE: The specific effects of exercise on pulmonary hypertension-right ventricular failure (PH-RVF) patients remain poorly understood, especially severe PH. Our group has previously established a large animal model of pulmonary hypertension-right ventricular failure (PH-RVF). We combined this model with an exercise platform to improve our understanding of exercise on PH-RVF and the impact of mechanical circulatory support (MCS) on exercise tolerance.
METHODS: A 67-kg healthy sheep was acclimated to a livestock treadmill. Following our previously published protocol for a sheep PH-RVF model, we ligated the left pulmonary artery, placed an inflatable adjustable silicone band on the main PA, and inserted an indwelling catheter in the RV outflow tract. The pressure in the adjustable silicone band was increased weekly an average of 100-150 mmHg to create a progressive model of PH-RVF over the course of 8 weeks. During this period, the sheep completed a weekly exercise routine on the treadmill at speeds ranging from 0-1.1 m/s. Mixed venous oxygenation (SvO2) and RV systolic pressure [(RVSP), mmHg)] were measured during each treadmill session. Following the 8-week period of progressive cuff inflation and exercise regimen, a re-operative thoracotomy was performed, and the sheep was placed on a right atrial to left atrial (RA-LA) ECMO circuit at a blood flow ranging from 2 L/min to 3.5L/min. The sheep completed the full exercise routine 3 days post op. The same parameters including SVO2 and RVSP were measured during this exercise routine with the MCS circuit.
RESULTS: As the PH-RVF model progressed, the sheep experienced more difficulty completing the exercise routine as evidenced by clinical appearance (gait ataxia, increased respiratory rate, pallor) and decreasing SVO2. At rest, the week 1 SVO2 and RVSP were 84.2% and 80mmHg respectively, compared to week 8 resting SVO2 and RVSP of 73.4% and 59mmHg. By week 8, the sheep was unable to complete the exercise routine. The sheep was able to complete the entire routine after the attachment of the extracorporeal circuit. MCS support resulted in a 18.8%% increase in SVO2 at the same speed, from 52.1% to 70.9%. RVSP during exercise while on MCS support ranged from 45 to 83 mmHg with a mean of 60. Total distance traveled during exercise was 1197 meters at week 8 of the model without MCS versus 3600 meters with MCS implant, a 117% increase.
CONCLUSION: Intervention with RA-LA MCS during exercise is feasible in a large animal model of PH-RVF and improves physiologic performance of a protocolized exercise routine.
Authors
Victoria Simon (1), Michael Cortelli (2), Carl Johnson (3), Kaitlyn Tracy (2), Timothy Harris (3), William Tucker (2), TiOluwanimi Adesanya (2), Avery Fortier (2), Elizabeth Simonds (1), Mark Petrovic (2), Briana Bernicker (4), Gabriella Glomp (4), David J. Skoog (5), Keith Cook (6), Eric Austin (2), Erika Rosenzweig (7), Garrett Coyan (8), Ashish Shah (4), Caitlin Demarest (1), Matthew Bacchetta (2), Rei Ukita (9)
Institutions
(1) Vanderbilt University Hospital, Nashville, TN, (2) Vanderbilt University Medical Center, Nashville, TN, (3) N/A, N/A, (4) Vanderbilt University, Nashville, TN, (5) 3. Advanced Respiratory Technologies, Inc., Pittsburgh, PA, Pittsburgh, PA, (6) Carnegie Mellon University, N/A, (7) Columbia University Irving Medical Center – New York Presbyterian, New York, NY, (8) University of Pittsburgh Medical Center, Pittsburgh, PA, (9) N/A, Nashville, TN
METHODS: A 67-kg healthy sheep was acclimated to a livestock treadmill. Following our previously published protocol for a sheep PH-RVF model, we ligated the left pulmonary artery, placed an inflatable adjustable silicone band on the main PA, and inserted an indwelling catheter in the RV outflow tract. The pressure in the adjustable silicone band was increased weekly an average of 100-150 mmHg to create a progressive model of PH-RVF over the course of 8 weeks. During this period, the sheep completed a weekly exercise routine on the treadmill at speeds ranging from 0-1.1 m/s. Mixed venous oxygenation (SvO2) and RV systolic pressure [(RVSP), mmHg)] were measured during each treadmill session. Following the 8-week period of progressive cuff inflation and exercise regimen, a re-operative thoracotomy was performed, and the sheep was placed on a right atrial to left atrial (RA-LA) ECMO circuit at a blood flow ranging from 2 L/min to 3.5L/min. The sheep completed the full exercise routine 3 days post op. The same parameters including SVO2 and RVSP were measured during this exercise routine with the MCS circuit.
RESULTS: As the PH-RVF model progressed, the sheep experienced more difficulty completing the exercise routine as evidenced by clinical appearance (gait ataxia, increased respiratory rate, pallor) and decreasing SVO2. At rest, the week 1 SVO2 and RVSP were 84.2% and 80mmHg respectively, compared to week 8 resting SVO2 and RVSP of 73.4% and 59mmHg. By week 8, the sheep was unable to complete the exercise routine. The sheep was able to complete the entire routine after the attachment of the extracorporeal circuit. MCS support resulted in a 18.8%% increase in SVO2 at the same speed, from 52.1% to 70.9%. RVSP during exercise while on MCS support ranged from 45 to 83 mmHg with a mean of 60. Total distance traveled during exercise was 1197 meters at week 8 of the model without MCS versus 3600 meters with MCS implant, a 117% increase.
CONCLUSION: Intervention with RA-LA MCS during exercise is feasible in a large animal model of PH-RVF and improves physiologic performance of a protocolized exercise routine.
Authors
Victoria Simon (1), Michael Cortelli (2), Carl Johnson (3), Kaitlyn Tracy (2), Timothy Harris (3), William Tucker (2), TiOluwanimi Adesanya (2), Avery Fortier (2), Elizabeth Simonds (1), Mark Petrovic (2), Briana Bernicker (4), Gabriella Glomp (4), David J. Skoog (5), Keith Cook (6), Eric Austin (2), Erika Rosenzweig (7), Garrett Coyan (8), Ashish Shah (4), Caitlin Demarest (1), Matthew Bacchetta (2), Rei Ukita (9)
Institutions
(1) Vanderbilt University Hospital, Nashville, TN, (2) Vanderbilt University Medical Center, Nashville, TN, (3) N/A, N/A, (4) Vanderbilt University, Nashville, TN, (5) 3. Advanced Respiratory Technologies, Inc., Pittsburgh, PA, Pittsburgh, PA, (6) Carnegie Mellon University, N/A, (7) Columbia University Irving Medical Center – New York Presbyterian, New York, NY, (8) University of Pittsburgh Medical Center, Pittsburgh, PA, (9) N/A, Nashville, TN