Preclinical Test of an Electro-Mechanical Implantable Left Ventricular Assist System

Abstract

Background and Objectives: Ventricular assist systems are used in patients with end-stage heart failure to prolong life or as a bridge to transplantation. Several types of ventricular assist systems have been developed and they are now being used. We developed a new Biomedlab® electro-mechanical implantable ventricular assist device (IVAD) and we performed in vivo experimentation to evaluate the durability and safety of the device, as well as its hematologic effect.

Materials and Methods: We implanted the newly developed IVAD in the pre-peritoneal cavity of 5 Hallstein calves. The inflow tract was inserted through the left ventricular apex, and the outflow tract was anastomosed to the descending thoracic aorta. Postoperatively, we administered heparin intravenously for 2 days after implantation, and then we administered warfarin sodium daily. We examined, both preoperatively and postoperatively, the serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), blood urea nitrogen (BUN), creatinine, lactate dehydrogenase (LDH), haptoglobin, fibrinogen, whole blood hemoglobin, hematocrit, prothrombin time (PT), partial thromboplastin time (PTT) and the plasma hemoglobin. We also recorded the assisted flow rate and the hemodynamic parameters of the animals. After IVAD implantation, the international normalized ratio (INR) was monitored and maintained in the range of 3.5-4.0. Postoperatively, when any device-related problems developed, we euthanized the animals and performed autopsy.

Results: After IVAD implantation, the 5 calves lived for 1, 6, 3, 12 and 21 days, respectively. Three of them were euthanized due to mechanical problems such as electrical shorts, and the other calves died suddenly due to blood leakage at the outflow tract on postoperative day 21 and graft disconnection on postoperative day 3, respectively. Autopsy was performed in all the animals and there was no evidence of thromboembolism or hemorrhage in the kidney, liver or lungs. There was also no evidence of thrombosis on the valve, blood sac or inflow/outflow tract. Hematologic and chemical examinations revealed mild hemolysis in the early postoperative period, which stabilized with minimal hemolysis. There was no organ dysfunction.

Conclusion: Our newly developed Biomedlab® IVAD was feasible for implantation and it functioned well in a calf model. Although there were 3 mechanical problems, we did not find any device-related thrombosis and serious hemolysis. With this encouraging result, it may be possible to perform animal experiments with the final version of IVAD, after correcting the mechanical problems, to evaluate the device’s longterm durability and stability.