Masayuki Kinoshita

Influence of prolonged ventricular assistance on myocardial histopathology in intact heart

BACKGROUND The unloading effect of ventricular assistance on the injured myocardium may adversely affect the compensatory hypertrophy of the residual intact myocardium because myocardial protein synthesis is partly controlled by cardiac work. The influence of prolonged ventricular assistance on normal myocardium was evaluated from a pathologic point of view. METHODS A ventricular assist device was chronically implanted in 5 goats using left atrium-aorta bypass. The pumping ratio was fixed at 70 beats/min. Left ventricular biopsy samples were taken before and 1 month after assistance. RESULTS Although the volume densities of myocytes and interstitial tissue in the myocardium showed no significant changes after 1 month of support, the myocyte volume density to nuclear volume density ratio and the interstitial tissue volume density to nuclear volume density ratio decreased significantly (p < 0.01 and p < 0.05, respectively). A cross-sectional area of myocyte showed decreases of 20.9% to 49.5%, whereas the nuclear cross-sectional area showed no significant changes. In addition, myofibrillar volume density in the cytoplasm decreased from 54.9 +/- 2.3% to 49.1 +/- 4.4%. CONCLUSIONS The results indicate that long-term ventricular assistance in the intact heart leads to myocardial atrophy. This suggests that in the damaged heart subjected to prolonged unloading by ventricular assistance, there is the possibility of limiting compensatory hypertrophic changes in the residual intact myocardium.

Multi-institutional studies of the national cardiovascular center ventricular assist system: Use in 92 patients

A ventricular assist system (VAS) developed at the National Cardiovascular Center (NCVC) and produced by Toyobo Company has been clinically evaluated at 32 institutes. The system consists of a pneumatic and diaphragm-type pump, and a control-drive unit with an automatic bypass flow (BF) control system. The VAS was used in 85 adults and 7 children with acute, severe heart failure. Forty-eight patients were weaned from VAS, and 21 were long-term survivors. Heparin was not used when BF was above 2.0 L/min in an adult sized pump, and 0.8 in a pediatric one. Thrombus formation was noticed in the groove around the valve in eight cases, and in the pump in eight. Pump-originated serious complications were not seen. Hematologic and biochemical findings revealed that the VAS did not directly affect the major organs. The control-drive unit, including the automatic BF control system, functioned accurately, with less manpower, securing reliable control over the circulation. Two major causes of death were irreversible heart failure, and multiple organ failure, which resulted from delayed application. In conclusion, the NCVC-type VAS has been found effective and reliable, less thrombogenic, and requiring less manpower for its clinical use.

Experimental evaluation and clinical application of a pediatric ventricular assist device

A pneumatic pediatric ventricular assist device (VAD) with a stroke volume of 20 ml has been developed to treat post-operative heart failure (HF), and maintain transplant candidates. The polyurethane VAD has two #21 Bjork-Shiley valves and the internal diameter of the cannula is either 6 or 8 mm. Hemodynamic effects of a left ventricular assist device (LVAD) on a HF after Fontans procedure model, and those of a right ventricular assist device (RVAD) on right HF with pulmonary hypertension model, were investigated in acute experiments with four and five dogs, respectively. In the former, the pressure gradient across the lung and cardiac output (CO) increased with an LVAD; right atrial pressure decreased and CO increased with an RVAD in the latter. The pump was implanted as an LVAD in 8 young goats, 9-22 kg in weight, for 4-10 weeks and favorable in vivo performance was demonstrated. The VAD system was applied as an LVAD to two postcardiotomy patients, a 12 kg boy with a ventricular septal defect, and a 13 kg boy with an endocardial cushion defect. In these cases, CO was well maintained at the level of 2.5-4.1 L/min/m2 for three and seven days, respectively, and the pump was removed. In conclusion, this VAD will become a promising circulatory support system for pediatric uses.

Myocardial mechanics, energetics, and hemodynamics during intraaortic balloon and transvalvular axial flow hemopump support with a bovine model of ischemic cardiac dysfunction.

Unlike the mechanisms of intraaortic balloon pump (IABP) support, the mechanisms by which transvalvular axial flow Hemopump (HP) support benefit dysfunctional myocardium are less clearly understood. To help elucidate these mechanisms, hemodynamic, metabolic, and mechanical indexes of left ventricular function were measured during conditions of control, ischemic dysfunction, IABP support, and HP support. A large animal (calf) model of left ventricular dysfunction was created with multiple coronary ligations. Peak intraventricular pressure increased with HP support and decreased with IABP support. Intramyocardial pressure (an indicator of intramyocardial stress), time rate of pressure change (an indicator of contractility), and left ventricular myocardial oxygen consumption decreased with IABP and HP support. Left ventricular work decreased with HP support and increased with IABP support. During HP support, indexes of wall stress, work, and contractility, all primary determinants of oxygen consumption, were reduced. During IABP support, indexes of wall stress and contractility were reduced and external work increased. These changes were attributed primarily to changes in ventricular preload, and geometry for HP support, and to a reduction in afterload for IABP support. These findings support the hypothesis that both HP and IABP support reduce intramyocardial stress development and the corresponding oxygen consumption, although via different mechanisms.

Regulation of coronary circulation during left ventricular assist

Regulatory mechanisms of coronary circulation during left ventricular assist (LVA) were studied in chronic experiments using adult goats. In normal heart studies (n = 3), circumflex coronary artery flow (CxF) and endocardial blood flow (MBF) decreased in proportion to decrease of tension time index (TTI). Mean CxF/TTI was constant at 0.22, whether the LVA functioned or not. In the left anterior descending branch ligation model (AMI) study (n = 2), CxF decreased according to decrease of TTI throughout the experiment, if the bypass ratio was kept within a normal range of systemic pressure. Mean CxF/TTI was maintained at approximately 0.21 by LVA, fell to 0.16 when LVA was turned off during the early stages. Coronary circulation during LVA was regulated by oxygen demand if systemic circulation was maintained, and LVA improved oxygen demand-supply balance in failing hearts.

Pulmonary function in a non-pulsatile pulmonary circulation.

The authors suggested that a mammal immediately accommodates well to nonpulsatile flow in the systemic circulation. In the current study, nonpulsatile pulmonary blood flow using a centrifugal pump was established in chronic models to analyze its influence on the pulmonary circulation. A pulsatile right ventricular assist device (RVAD) was implanted to draw blood from both the right atrium and ventricle and send blood to the pulmonary artery in six goats. After 2 weeks, the pulsatile pump was quickly replaced with a centrifugal pump without anesthesia, and a 100% non-pulsatile pulmonary blood flow was obtained. Cardiac output was kept at 80-120 ml/kg/min during the experiments. No changes were observed in hemodynamic parameters, including pulmonary arterial pressure, pulmonary vascular resistance index, and blood gas data, after the immediate depulsation of the pulmonary blood flow. There was also no significant change in the ventral to dorsal tissue blood flow ratio of the lower lobe of the right lung, which was calculated by a colored microsphere method, between pulsatile and non-pulsatile pulmonary blood perfusion. These results suggest that pulmonary function, including blood flow distribution, is not affected by non-pulsatile pulmonary circulation for periods up to 14 days.

A motor integrated regenerative pump as the actuator of an electrohydraulic totally implantable artificial heart.

The authors have developed a new actuator to drive an electrohydraulic totally implantable artificial heart. The basic concept of this artificial heart is that the blood pumps are implanted in the thorax and an actuator is placed separately in the abdominal region. The actuator is a regenerative pump that pumps fluids against high pressures and is thin enough for easy implantation. The rotor-magnet of the brushless DC motor is mounted on the impeller of the pump to miniaturize the actuator and reduce the number of moving parts. The height, diameter, and weight of the actuator are 32.5 mm, 73 mm, and 360 g, respectively. A pair of oil ports is connected to the left and right blood pumps with mesh reinforced tubes filled with silicone oil. The blood pumps are alternately driven by bidirectional rotation of the motor. Performance of the system was evaluated in in vitro and in vivo experiments. Maximum output of the right heart was 6.7 L/min in both experiments. Systemic circulation was well maintained in acute animal experiments using 49 and 50 kg goats. The feasibility of the actuator was confirmed.

An abdominally placed, implantable left ventricular assist system for long-term use

An implantable left ventricular assist system was developed for long-term use. The system includes an implantable blood pump, a portable control drive unit (CDU), and a monitoring system. The blood pump was designed to be positioned in the left abdominal wall and was made of segmented polyether polyurethane. A percutaneous drive line connected it to the external CDU. The CDU included a continuous pump performance monitoring system that measured electrical impedance between the two metal connectors of a blood pump. In animal experiments using six adult goats, the pump was installed between the left ventricular apex and the descending aorta, and it was placed in the abdominal wall. No antithrombogenic agents were administered during the course of the experiment. This LVAS was easy to use and provided stable hemodynamic conditions for > 8 weeks. Pump output (Op), estimated by impedance, was linearly related to Op measured with an electromagnetic flowmeter. Pump performance was effectively estimated, and the fill-empty drive was well controlled by impedance. There were no significant abnormal hematologic or blood chemistry values, no signs of infection around the pump pocket (except in one animal), and no obvious thromboembolic symptoms. Maximum flow was 6.7 L/min with use of a prototype portable CDU (dimensions, 500 x 168 x 435 mm; weight, 16 kg). In conclusion, this LVAS is promising for long-term clinical use.

An electrohydraulic ventricular assist system with a linear actuator.

An electrohydraulic ventricular assist system with a linear actuator was developed, and in vitro and in vivo evaluations were performed. During in vitro evaluations this system could yield 5.6 L/min of pump flow against a mean afterload of 100 mmHg. Durability tests were performed for more than 4 months. The system was implanted in three goats and a maximum pump flow of 4.2 L/min was obtained against a mean afterload of 100 mmHg, and 3.2 L/min against 130 mmHg. These evaluations have proven that the system can maintain stable hemodynamics under various conditions.

An Electrohydraulic Totally Implantable Artificial Heart with a Motor-Integrated Regenerative Pump

The ultimate goal of this study is the development of a totally implantable artificial heart. Since 1957, many investigators have been working to develop such a device; however, this heart is currently still under investigation [1]. Several technical hurdles must be overcome for the development of such a system, one of these being the size limitation of the device, which is determined by the dimensions of the patient’s thorax. To overcome the problem, we are developing an electrohydraulic totally implantable artificial heart for which the blood pumps and an energy converter can be placed separately in the body. This system has the following advantages: 1. The space of the thoracic cavity is used only for the blood pumps. 2. Blood pumps which have already been developed and evaluated as pneumatic devices over the past several years can be used. 3. Implantation is an easy procedure with divided right and left pumps. Here we report a newly developed total artificial heart.