Cardiogenic shock (CS) is a serious condition of reduced cardiac output (CO) with a mortality as high as40-50%. 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 membraneoxygenation 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 withthe native heart for counter pulsation. Our enabling technologies that form the sppVAD system are a valvedsingle 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 counter pulsation pumping. W-Z Biotech made an initial prototype of sppVAD system, which had 3.1 L/min pumping flow against80 mm Hg after load 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 pumpvolume. 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 CSsheep 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 vivoanimal studies will be done at University of Kentucky. Upon project completion, the commercialized sppVADsystem will provide total LV support to severe CS patients via only a minimally invasive single cannulation.
Public Health Relevance Statement: We are proposing to develop a compact, single port, pulsatile ventricular assist device (sppVAD) for total left ventricle (LV) support that employs a minimally invasive single cannulation technique for implantation. 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 sppVAD system will provide total LV support via only a minimally invasive single cannulation to bridge the severe cardiogenic shock patient to recovery, further treatment, long-term LVAD or heart transplantation, potentially improving outcomes.
Project Terms: Alloys ; Animals ; Aorta ; ascending aorta ; Biotechnology ; Biotech ; Blood ; Blood Reticuloendothelial System ; Blood Circulation ; Bloodstream ; Circulation ; Carbon Dioxide ; CO2 ; Carbonic Anhydride ; Cardiac Output ; heart output ; Low Cardiac Output ; Counterpulsation ; Respiratory Diaphragm ; Diaphragm ; Engineering ; Extracorporeal Membrane Oxygenation ; Goals ; Heart ; Heart Transplantation ; Cardiac Transplantation ; Heart Grafting ; cardiac graft ; cardiovascular transplantation ; heart transplant ; Housing ; Kentucky ; Lung ; Lung Respiratory System ; pulmonary ; Memory ; mortality ; Multiple Organ Failure ; MOF syndrome ; Multiple Organ Dysfunction Syndrome ; multiorgan failure ; multiple organ system failure ; Myocardial Infarction ; Cardiac infarction ; Myocardial Infarct ; cardiac infarct ; coronary attack ; coronary infarct ; coronary infarction ; heart attack ; heart infarct ; heart infarction ; Patients ; Perfusion ; Polyurethanes ; Ostamer ; Pellethane ; Polyisocyanates ; Publications ; Scientific Publication ; Research ; research and development ; Development and Research ; R & D ; R&D ; Safety ; Self-Help Devices ; Assistive Technology ; assisted device ; assistive device ; Cardiogenic Shock ; Stress ; Stroke ; Apoplexy ; Brain Vascular Accident ; Cerebral Stroke ; Cerebrovascular Apoplexy ; Cerebrovascular Stroke ; brain attack ; cerebral vascular accident ; cerebrovascular accident ; Technology ; Testing ; Thinness ; Leanness ; Thoracotomy ; chest wall incision ; thorax incision ; Universities ; Work ; Organ ; blood pump ; Pump ; Left ; Apical ; Clinical ; Phase ; Left ventricular structure ; Left Ventricles ; Recovery ; Withdrawal ; artificial lung ; mechanical ; Mechanics ; Scientist ; Hour ; Complex ; Techniques ; System ; Cannulas ; Thoracic Surgery ; chest surgery ; Thoracic Surgical Procedures ; Surgeon ; experience ; membrane structure ; Membrane ; Performance ; simulation ; novel ; Devices ; Abscission ; Extirpation ; Removal ; Surgical Removal ; resection ; Excision ; Cannulations ; preventing ; prevent ; Artificial Heart Ventricle ; Artificial Ventricles ; Ventricle-Assist Device ; ventricular assist device ; Data ; in vivo ; Laboratory Animal Production and Facilities ; Research Animal Facility ; Small Business Innovation Research Grant ; SBIR ; Small Business Innovation Research ; Cardiac ; Development ; developmental ; Pathway interactions ; pathway ; design ; designing ; innovation ; innovate ; innovative ; Resistance ; resistant ; multidisciplinary ; implantation ; prototype ; minimally invasive ; in vitro testing ; flexibility ; flexible ; hypoperfusion ; invention ; improved outcome ; myocardial injury ; injury to the myocardium ; sheep model ; ovine animal model ; ovine model ;
