Cardiogenic shock (CS) is a serious condition of reduced cardiac output (CO) with a mortality as high as 40-50%. In severe CS, end organ hypoperfusion from low CO causes multi-organ failure and elevated left ventricle (LV) preload increases LV wall stress. For severe CS, venoarterial extracorporeal membrane oxygenation is most often used and is fastest way to reestablish circulation, but it fails to unload LV in > 50% of these patients. Percutaneous mechanical circulatory support (MCS) devices are used in severe CS but may not fully stabilize circulation. Non-percutaneous MCS devices supply total cardiac support but require open chest surgery for installation. Our goal is to develop a compact, single port, pulsatile ventricular assist device (sppVAD) for total LV support that employs a minimally invasive single cannulation technique for implantation. Compared to a continuous flow LVAD, our sppVAD system may further unload the LV when synchronized with the native heart for counterpulsation. Our enabling technologies that form the sppVAD system are a valved single lumen cannula (VSLC) and a valveless single port diaphragm displacement pump (spDDP). Our innovative sppVAD system features: 1) Minimally invasive trans-apical to aorta installation by one VSLC cannulation through small left thoracotomy; 2) Smaller spDDP without inlet/outlet valves and large dead space; 3) Lower blood resistance due to shorter pathway through LV via the VSLC that serves as both inlet and outlet cannula; 4) Dependable total LV unloading; 5) Potential LV internal/stroke work decrease with counterpulsation pumping. W-Z Biotech made an initial prototype of sppVAD system, which had 3.1 L/min pumping flow against 80 mm Hg afterload in mock loop testing. Our objective in this Phase I SBIR is to develop/fabricate new working prototype of sppVAD system (VSLC and spDDP) and to test sppVAD system prototype in mock loop and severe CS sheep model. Specific Aim 1: To develop/fabricate/bench test new working prototype of sppVAD system (VSLC and spDDP). The 22 Fr VSLC main body will be memory alloy wire reinforced polyurethane (PU). Two one-way inlet valves on VSLC wall will be in LV for blood withdrawal. Two one-way outlet valves on VSLC wall near tip and a one-way outlet valve on VSLC tip will be in ascending aorta for blood delivery. The spDDP will have rigid PU housing, a soft, flexible PU diaphragm membrane, and a 50 mL pump volume. Only one 3/8” blood port will be made on spDDP for direct connection to VSLC. This sppVAD system will be tested in a bench mock loop. Specific Aim 2: To test sppVAD system prototype in a severe CS sheep model. Our severe CS sheep model will be used to test our sppVAD system prototype for ease of insertion/deployment, LV unloading performance, counterpulsation capacity, and 6 hr reliability (n=5). The sppVAD system prototype design/fabrication/in vitro testing will be done at W-Z Biotech while the in vivo animal studies will be done at University of Kentu...