Blood Trauma, Vascular Remodeling, and Vasoregulation with Total Body Continuous Versus Pulsatile Artificial Circulation

Project Abstract Left ventricular assist device support is standard therapy for patients with advanced, life-threatening heart failure. However, current-generation impeller-based blood pumps have introduced a new “non-pulsatile” physiology with frequent adverse events. Lack of pulsatility contributes to blood trauma, endothelial and arterial remodeling, and abnormalities in vasoregulation that predispose patients to bleeding, thrombosis, diastolic hypertension, and stroke. Cyclic speed modulation in which device impeller speed is rapidly increased/decreased has been developed to generate pulsatile blood flow. This emerging technology has potential to combine durability of impeller-driven devices with physiologic benefits of pulsatility in order to reduce adverse events and improve quality of life for patients with artificial circulation devices. To date, no investigation has characterized (patho)physiologic effects of total-body pulsatile versus non-pulsatile blood flow with the same device. The BiVACOR total artificial heart is a first-of-its-kind, impeller-based total artificial heart with the ability to generate continuous (non-pulsatile) or pulsatile blood flow through cyclic impeller speed modulation. In a chronic bovine model, we propose to investigate in vivo effects of non-pulsatile versus pulsatile flow with the BiVACOR on blood trauma, arterial remodeling, and vasoregulation. We anticipate that compared to non-pulsatile support, pulsatile flow will 1) reduce blood trauma, 2) prevent pathologic changes in endothelial and arterial wall architecture and function, and 3) maintain normal vasoregulation during postural changes, transition to exercise, sleep, and other activities of daily living. Data will provide insight into pathophysiologic mechanisms of adverse events in patients with impeller-based blood pumps. Findings will also be useful for the development of artificial pulsatility algorithms that mimic physiologic pulsatility in order to minimize blood trauma, prevent arterial remodeling, and appropriately modulate vasomotor tone during daily activities.