BIO3: Durable Right Heart Mechanical Support System: A Multi-Day Proof-of-Concept Study in Pulmonary Hypertension Sheep (2022)

Introduction: Pulmonary hypertension (PH) is a pulmonary vascular disease that progressively strains the right heart. The disease is generally irreversible and ultimately leads to right heart failure. Thus, the only long-term effective treatment is lung transplantation. Unfortunately, the donor lung pool is limited, and PH patients have one of the longest waiting times for lung transplantation. End-stage PH patients could benefit from a durable, wearable platform for mechanical circulatory support to alleviate their physiologic deficits. Toward this end, our group has established a compact mechanical support system consisting of a VAD-quality pump coupled with a membrane oxygenator. Furthermore, we previously showed that a right atrium-to-left atrium configuration provides effective support for PH-induced right ventricular failure (PH-RVF). Here, we present our proof-of-concept study using a multi-day large animal model supported by this system. Methods: Three adult sheep (weight = 84 ± 7 kg) underwent previously described PH-RVF model consisting of left pulmonary artery (PA) ligation and progressive main PA cuff occlusion. After the chronic PH model of 64 ± 6 days, the animals were cannulated for mechanical cardiopulmonary support under a right atrium-to-left atrium (RA-LA) configuration. 25Fr Biomedicus venous drainage cannula was placed in the RA via the left jugular vein, and 17-20 Fr Biomedicus cannula was placed in the LA through a mini left thoracotomy. The circuit consisted of a HeartAssist5 (ReliantHeart, Houston TX) pump and Nautilus (N=3, MC3, Ann Arbor, Michigan) as a membrane oxygenator. The animal was then recovered in a custom-designed stanchion cage for chronic monitoring. Circuit parameters were recorded, and blood samples were drawn daily. Results: Three sheep with PH were used for this preliminary study (induced RV systolic pressure 93 ± 10 mmHg before cannulation). Two of the three studies lasted for the planned duration of seven days. One study was terminated early on the second post-operative day (POD) due to intrathoracic bleeding. Among the two seven-day trials, the HeartAssist5 pump provided stable flow of 2.69 ± 0.43 L/min at pump speed of (11.97 ± 0.68) x 103 RPM, while the PA flow was 3.52 ± 1.09 L/min (Figure 1A) (i.e., the circuit offloaded about 43% of the total cardiac output). The oxygenator circuit provided sufficient gas exchange and maintained acid-base balance at a minimal sweep gas flow of 0.5 L/min (Figure 1B, C). One sheep was able to ambulate with the wearable support system on the seventh day of mechanical support (Figure 2). Conclusion: This study serves as a proof-of-concept for long-term wearable support for PH-RVF patients. The circuit could consistently offload over 40% of the cardiac output. Left atrial cannula size is likely the limiting factor for maximal achievable blood flow with this system. Further innovation is needed in surgical techniques to implement circuit support. Figure 1. Longitudinal trends during multi-day support study: A) Circuit and pulmonary artery blood flows; B) Sweep gas flow rate; C) Blood lactate level. N = 2-3 for Days 0-2, and N =2 for Days 3-7. Figure 2. Pulmonary hypertension sheep ambulating with the wearable mechanical support technology.