structured-exercise-regimen-pulmonary-hypertension-right-ventricular

Structured Exercise Regimen in Pulmonary Hypertension-Right Ventricular Failure in an Ovine Model

Right heart failure (RHF) is a significant cause of morbidity and mortality from pulmonary hypertension (PH). To better understand the pathophysiology and ...

Decompensated right ventricular failure (RVF) in pulmonary hypertension (PH) is fatal, with limited medical treatment options. Developing and testing novel therapeutics for PH requires a clinically relevant large animal model of increased pulmonary vascular resistance and RVF. This manuscript describes the method to induce an ovine PH-RVF model that utilizes left pulmonary artery (LPA) ligation, progressive main pulmonary artery (MPA) banding, and insertion of an RV pressure line for monitoring. The PA cuff and RV pressure tubing are connected to subcutaneous access ports. This model of PH-RVF is a versatile platform to control not only the disease severity, but also the RV's phenotypic response. Subjects undergo progressive PA band adjustments twice per week for approximately 9 weeks with sequential measures of RV pressure, PA cuff pressures, and mixed venous blood gas (SvO). Subjects can further be exercised on a livestock treadmill while hemodynamic parameters are captured. At the initiation and endpoint of this model, ventricular function and dimensions are assessed using echocardiography. In this model, RV mean and systolic pressure increased to 28 ± 5 and 57 ± 7 mmHg at week 1, and further to 44 ± 7 and 93 ± 18 mmHg by week 9, respectively. Echocardiography demonstrates characteristic findings of PH-RVF, notably RV dilation, increased wall thickness, and septal bowing. The rate of PA banding has a significant impact on SvO and thus the model can be titrated to elicit varying RV phenotypes. When the PA cuff is tightened rapidly, it can lead to a precipitous decline in SvO, leading to RV decompensation, whereas a slower, more paced strategy leads to an adaptive RV stress-load response that maintains physiologic SvO. A faster rate of PA banding will also lead to more severe liver fibrosis. The addition of controlled exercise provides a useful platform for assessing the effects of physical exertion in a PH-RVF model. This chronic PH-RVF model provides a valuable tool for studying molecular mechanisms, developing diagnostic biomarkers, and evaluating mechanical circulatory support systems.

A Dynamic Sheep Model to Induce Pulmonary Hypertension and Right Ventricular Failure.

Chronic obstructive pulmonary disease (COPD) is the most prevalent chronic end stage lung disease. There are few long-term treatment options for end stage COPD due to donor lung scarcity. Durable artificial lung therapies may provide alternatives for long-term respiratory support. Veno-venous extracorporeal membrane oxygenation can provide physiologic support, but current cannulation configurations are suboptimal for durable support.

Article	Year
A Dynamic Sheep Model to Induce Pulmonary Hypertension and Right Ventricular Failure. Methods in molecular biology (Clifton, N.J.)\| PubMed ID: 38676898	2024
Determining an optimal central cannulation strategy for ambulatory veno-venous extracorporeal life support. The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation\| PubMed ID: 41949527	2026

Courtney Cagnolatti

Biography

JoVE Journal Publications

Other Publications