Toshiyuki Shinohara

Development of a flexible inflow cannula with titanium inflow tip for the NEDO biventricular assist device.

A newly designed flexible inflow cannula has been developed for a biventricular assist device (BVAD). The inflow tip was designed for long-term ventricle drainage. Considering the anatomic differences between the right and left ventricles, a flexible inflow cannula, as a mass production model with a titanium tip, was developed and investigated in chronic BVAD animal experiments using the NEDO permanently implantable centrifugal blood pump. These flexible inflow cannulae consist of flexible plastic tubing with wire supported, titanium left and right tips. The right titanium inflow tip was designed with inner and outer stoppers to be inserted into the right ventricle wall and a beak shape to avoid sucking. The left tip was designed to be inserted into the left ventricle cavity. Five chronic BVAD bovine studies were performed to investigate the new beak shaped titanium tip. In these studies, the new beak shaped titanium tip and cannula prevented stenosis by a proliferation of pseudoneointimal, and supplied adequate blood flow to the pump without sucking. This newly designed inflow cannula with the beak shaped titanium tip was successfully implanted for 90 days.

Physiological adaptation to a nonpulsatile biventricular assist system.

Physiological adaptation of the recipient to a nonpulsatile biventricular assist system (NPBVAS) is not well understood. The aim of this study is to evaluate the physiological adaptation of experimental animals after NPBVAS implantation. Since May 2001, four long-term NPBVAS implant experiments in calves were performed. The blood gas and hemodynamic data were analyzed retrospectively. An additional prospective experiment was performed to confirm retrospective findings. All calves (n = 5) lived longer than 5 weeks without complication. In retrospective analysis, there was not a correlation between the O2 content and total blood flow in the pulmonary artery during the 1st postoperative week, but they began to correlate within the 2nd postoperative week. Then, there was a strong correlation after the 3rd postoperative week (r = 0.753). In the prospective experiment, O2 content related to total pulmonary flow after 2 weeks (r = 0.732) was the same as in the retrospective study. Most of the hemodynamic parameters studied became normalized after 14 days. In addition, easier controllability of the blood pumps was demonstrated after the 2nd postoperative week in all five experiments. Experimental results suggested that the native healthy heart accepted NPBVAS by reducing its cardiac output in 2 weeks. In addition, complicated control of the BPVAS was not necessary after 2 weeks of implantation. These results demonstrate the possibility of physiological adaptation to the NPBVAS being established within 2 postoperative weeks.

Ten-year NEDO BVAD development program: Moving forward to the clinical Arena

Since 1995, the Baylor Group has been developing a totally implantable NEDO BVAD system. This 10-year program was completed in March 2005, and preparation for clinical trials is underway. This article summarizes the entire 10-year NEDO program and describes the strategy for clinical trials. The project aimed to achieve: (1) dual centrifugal pumps with the ability of full biventricular support, (2) a compact system implantable into small adults, (3) a totally implantable system with transcutaneous energy transmission system (TETS), (4) a durable system with a lifetime of over 5 years, and (5) a system free of thrombus and with minimal hemolysis. The final goals are to complete preclinical system evaluations and commence the clinical trials in the near future. In vitro studies have demonstrated a pump capacity of over 8.5 l/min and an Index of Hemolysis of <0.004 g/100 l. The pump-bearing life expectancy was over 5 years. To date, eight pumps endured in vivo studies of over 3 months without complications, including thromboembolic events. The in vitro endurance studies of eight pumps are longer than 1 year. There were no mechanical malfunctions or pump failure. A stepwise clinical trial is being planned: Step1, a wearable BVAD/VAD will be clinically studied; Step 2, the BVAD/VAD will be implanted intracorporeally without TETS; and, Step 3, a totally implantable system will be clinically evaluated. The NEDO BVAD system has completed preclinical testing. Clinical trial preparation is underway.