Search

A miniaturized video camera system integrated with a scaffold for blood vessels and tissue induction that is implantable into an animal body was developed. A small autofocus camera with USB interface was used as an imaging device. A close-up lens was added to reduce the focusing point. Also 45-degree reflecting prism was added for the compact system design. A fabric poly-glycolic acid sheet of 0.3 mm thickness was used as a scaffold. The observation area was about 8 x 6 mm and the tissue was induced from sideways. The camera was implanted into a muscular layer of a goat for more than 9 weeks to observe the skeletal muscle induction. Tissue induction to the scaffold started from third week and it took about 9 weeks to cover the entire area by the tissue, Vigorous angiogenesis was observed at the front region of tissue induction resulting dense distribution of capillary vessels and red blood cells. The density of capillary vessels reduced considerably behind the front region and arterioles and venules started to appear.

The undulation pump is a small continuous flow displacement-type blood pump. The undulation pump total artificial heart (UPTAH) is a unique implantable total artificial heart using undulation pumps. An adult female goat weighing 45.8 kg was used for implantation. The natural heart was replaced with the UPTAH under extracorporal circulation. The cardiac output (CO) was maintained to 100 ml/kg/min by controlling the right pump manually. To prevent lung edema, the left pump was controlled automatically to maintain the left atrial pressure below 20 mm Hg. The CO was maintained for 2 weeks. Thereafter, the CO gradually decreased. The goat suddenly died because of a brain stroke on the 31st postoperative day. At autopsy, the cavity of the left atrial cuff was almost occupied by the big pannus-like thrombus, which was thought to be the cause of death. Improvement of the atrial cuff is necessary to obtain longer survival and is being modified. No thrombus was found inside the pumps. However, temperature rise in a left motor was a problem. Improvement of the efficiency in a motor is necessary. Although many problems still remained, 1 month survival could be obtained with this unique implantable TAH using continuous flow displacement-type blood pumps.

Since 1986, percutaneous intradiscal laser nucleotomy (PILN) has been studied in the authors' laser laboratory. The purpose of this report is to develop PILN as an alternative to chemonucleolysis and percutaneous discectomy, which are currently applied, and to establish a safe, easy, accurate and short-time therapy method for lumbar disc herniation. After laser irradiation, intradiscal pressures (IDP) decreased and the nucleus pulposus was gradually replaced with cartilaginous fibrous tissue. The evaluation of heat distribution with thermocouples and thermography was done to determine safe optimum irradiating conditions and to develop a new double-lumen needle and a bare quartz fiber. Neodymium-yttrium-aluminum-garnet (Nd-YAG) laser devices have been improved for easy and safe use, and a new tip type pressure transducer has been made for improved therapeutic results using this new method.

An undulation pump is a special rotary blood pump in which rotation of a brushless DC motor is transformed to an undulating motion by a disc in the pump housing attached by means of a special link mechanism. In the blood pump, a closed line between the disc and housing moves from the inlet to the outlet by this undulating disc motion, which sucks and pushes the blood from the inlet to the outlet. Because the same phenomena occurs at both sides of the disc, a continuous flow is obtained when the motor rotational speed is constant. The pump flow pattern can be easily changed from continuous flow to pulsatile flow by controlling the motor drive current pattern. A seal membrane made of segmented polyurethane protects the blood from invading the link mechanism as well as the motor. UPTAH is fabricated with two undulation pumps and two brushless DC motors. Its size is 75 mm in diameter and 80 mm long, and it has one of the great advantage of no compliance chamber required in the system. UPTAHs were implanted under cardiopulmonary bypass (CPB) into the chest cavities of 16 goats, each weighing between 41 and 72 kg. No anticoagulant and antiplatelet agent was used after the surgery. The left atrial pressure was automatically controlled to prevent its elevation and sucking of the atrial wall into the atrial cuff. The following results were obtained: (1) UPTAHs fit well into all the goats; (2) the longest survival was 19.8 days, the cause of death was bleeding from the aortic anastomosis; (3) No thrombus was observed in the blood pump despite no anticoagulant use. Hemolysis depended upon the length of CPB during surgery. When CPB time was within 2 hours, hemolysis level returned to baseline within a few days of the surgery. UPTAH is a promising implantable TAH, because of its small size and easy controllability.

PROMOTION OF ANGIOGENESIS AND BLOOD SUPPLY RESTORATION IN ISCHEMIC SKELETAL MUSCLE OF RAT AFTER LOW-VOLTAGE ELECTRICAL STIMULATION

A total artificial heart (TAH) goat survived for 360 days on the new automatic control method (1/R control), in which the cardiac output of the TAH can be controlled through the cardiovascular center by making it function by reflecting the beta-adrenergic reaction in peripheral vascular resistance. This is thought to be the only long-term, real-time, measurable parameter by which information on the activity of the cardiovascular center can be received directly by the TAH system. In this goat, the hemodynamic parameters (RAP, AoP, and so forth) were kept within physiologic limits when control was stable, and the cardiac output was automatically increased in response to exercise, not unlike that in the natural heart. There were no abnormal blood chemical or hormone data except at end stage. Based on these results 1/R can be considered a physiologic control method for a TAH.

Atrial natriuretic peptide (ANP) was administered intravenously to three goats at a dose of 0.1 micrograms/kg/min for 40 min both before total artificial heart (TAH) placement and at 1, 7, and 14 postoperative weeks to determine whether exogenous ANP exhibits the same effect on animals with TAHs as it does on normal animals. No significant changes in the increases in plasma levels of ANP and cyclic guanosine monophosphate (c-GMP) were observed during ANP administration after TAH insertion. In preoperative animals, urine volume and urinary sodium excretion increased greatly during ANP administration, but this natriuretic effect was strongly suppressed in TAH animals. The changes in the decreases in arterial pressure and in central venous pressure (CVP) or right atrial pressure that occurred during the administration of ANP were not significant either pre- or post-operatively. Thus, only the natriuretic effect of ANP on the kidney was significantly suppressed in TAH animals, which might be due to some down-regulation of ANP receptors in the kidney, the production of some antagonists of ANP, sympathetic hypertonicity, or the elevation of CVP.

The blood compatibility of the jellyfish valve was studied. Artificial heart (AH) blood pumps incorporating jellyfish valves were connected to 18 goats as total artificial hearts (TAHs) and pumped for 1 to 125 days without anticoagulant or antiplatelet drugs. No thrombus was formed on the valve membrane or around the valve seat. Scanning electron microscopy showed almost no platelet deposition or microfibrin clot formation on the valve membrane, including its central region; the spokes of the valve seat were also free from platelet and microfibrin clots. No calcification was observed during these tests, and plasma free hemoglobin was between 2 and 7 mg/dl. The jellyfish valve revealed good blood compatibility, even without anticoagulant use.

A new pulsatile total artificial heart (TAH) system, combining a single centrifugal pump (CFP) with two three-way valves, was developed. One port of each three-way valve was connected to the inlet and outlet of a CFP, respectively. The other two ports of each valve ware connected to the right and left atrium, pulmonary artery, and aorta. The CFP can perfuse the pulmonary and systemic circulation alternately with pulsatile flow. A prototype system composed of a Sarns' CFP and solenoid valves was connected to a mock circulatory system resulting in 1) a pulsatile TAH that could be produced with a single CFP, 2) 5 L/min of pulsatile output with a normal flow wave form that can be obtained alternately on the right and left side by switching the solenoid valves, and 3) flow balance between the left and the right that could be controlled easily by the length of switching duration. This new system could be miniaturized and is feasible for a totally implantable TAH.

An artificial heart (AH) driving system, in which a sac or diaphragm type blood pump is liquid gas driven, is designed. The working mechanism of this system is as follows: 1) liquid gas is used for the driving source; 2) a liquid gas is stored in its liquid state in the circuit; 3) a liquid gas is vaporized, and the vaporizing pressure squeezes the blood pump, causing ejection of blood; 4) vaporized gas is aspirated and compressed by a small compressor to liquefaction through the heat exchanger, then negative pressure is applied to the blood pump and blood is aspirated; and 5) the blood pump is driven in this closed cycle. To demonstrate the mechanism of this system, a prototype was developed using Freon 114 as the liquid gas. In this system, the maximum flow of the AH at a 100 pulse per minute rate, was about 6.9 L/min, using a 90 ml sac type blood pump. The advantages of this AH driving mechanism are as follows: 1) a small system is available because pressure chambers are not necessary; 2) a biventricular system is available, with a single compressor; 3) no compliance chamber is necessary if the system is small enough to be implanted.

A total of 61 VASs developed in Tokyo University were evaluated at 21 institutions in the period 1985-1989 for determination of its reliability and effectiveness. The system is comprised of a pneumatic sack-type pump (Nippon Zeon Co.), and its driving console (Aishin Seiki Co.). The stroke volume of the pump is 40 ml and blood contacting surfaces are coated with Cardiothane. Ages of the patients (pts) ranged from 12-82 yrs (mean 58 yrs). VASs were used in the assist mode of LVAD (54 pts), RVAD (5 pts) and BVAD (2 pts). Most of the cases (58 pts) included postocardiotomy cardiogenic shock after surgery for ischemic (28 pts), valvular (22 pts), both ischemic and valvular (7 pts) and congenital (1 pt) heart diseases. Average duration of the assist ranged from 1 hr-20 days (mean 5.6 dys). The VADs could be weaned in 34 cases (56%) and among these, 13 cases (21%) survived to discharge from the hospital. Causes of death in cases which could be weaned from the VAD included multiple organ failure/due to delayed institution of adequate circulatory support, renal failure and systemic infection. Small and minute thrombus formations were noted in 7 cases however, no pump originated thromboembolism were complicated. No troubles of the pump including leakage nor breakage, no mechanical failures of the driving consoles were experienced in any of the cases. Thus, it is concluded that the system was proved to be clinically effective and reliable.

INFLUENCE OF THE FLOW PATTERNS ON THE MICROCIRCULATION OF THE BULBAR CONJUNCTIVA IN THE GOAT IMPLANTED A TOTAL ARTIFICIAL HEART

Current circulatory assist methods, such as intra-aortic balloon pumping (IABP), are not always adequate to save acute circulatory failure patients. Therefore, a stronger, percutaneously accessible method is required. We found that the combination of IABP and CP generated a profound circulatory assist effect, and we have consequently developed a new assist system in this study. A sac type blood pump with a volume of 20 ml and a single port without a valve, was developed for CP. In the mock circulatory test, a 20 ml stroke volume was obtained using a cannula with a 5 mm diameter under the following driving conditions: air pressure = 200/-100 mmHg; S/D = 50%; pulse rate = 100 bpm. In vivo experiments were performed using four mongrel dogs with body weights of 12-20 kg. A cannula for CP was inserted via the brachial artery or subclavian artery into the aortic root. The pump flow (PF), coronary artery flow (CF), renal arterial flow (RF), and aortic pressure (AP) were measured, and the combined effects of IABP and CP were compared with their individual effects. In the most effective case, a marked increase in diastolic AP (60%), cardiac output (40%), and CF (100%) was obtained by the combination of IABP and CP, which produced a remarkable effect compared with the single use of IABP and CP. There was no negative effect on RF by this assist method. As this new circulatory support system has many circulatory assist effects, and is percutaneously accessible, it will be available for clinical use.

High output AH pumping causes a marked decrease in hematocrit, as well as peripheral circulatory insufficiency. By the application of a new control method, based on our hypothesis of regulating the output of the pump, maintenance of normal outputs, long term survival, after total heart replacement, has improved from 10 days to 37 days, with the average survival of 18 days. In addition, the experimentsl animals' general condition has been markeldy improved.

We developed control system of total artificial heart (TAH) during exercise simulating the circulatory response of natural heart. The following procedures were taken to develop this system. 1) Measurement of hemodynamics and physical activity rate (PAR) of natural heart goats during treadmill exercise. 2) Estimation of cardiac output from PAR using a non-linear model. 3) Development of a pneumatic artificial heart (AH) driver with high speed controllability and a control unit to deliver CO calculated from PAR beat by beat. 4) Evaluation of the physiological condition of the TAH goat during exercise controlled by this system. Using this control method, CO of TAH goats was similar to that of natural heart goats during treadmill exercise. Hypertension was observed during exercise. This hypertension was considered to be derived from two causes. One was high inflow and outflow resistance of cannulae between AH pump and living body. The other was the disorder of peripheral circulatory control mechanism in TAH animal. Such as increased sympathetic activity, insufficient secretion of atrial natriuretic polypeptide (ANP) and decreased sensitivity of peripheral circulatory system with ANP.

By fixing the function of one ventricle, a total right heart bypass model can clarify the function and regulatory mechanism of the natural heart, and the etiology of abnormal hemodynamics in TAH animals such as increased CVP blood pressure and hepatic congestion. The pulmonary artery of a right heart bypass in a goat was clamped proximally; the pulmonary circulation was thus supplied entirely by the artificial heart and the systemic circulation by the natural heart. This model enabled studies of long-term effects of an artificial right heart on systemic circulation at a right heart output of 80-100 ml/kg/min; the response of the natural left heart to changes in output of the right heart; and the response of the natural left heart and artificial right heart to treadmill exercise. It was found that only slight increase in CVP or no increase in blood pressure was observed during the experiment (112 days); a rapid increase in output of the RAH resulted in an increase in left atrial pressure, stroke volume and output of the left ventricle, and a decrease in its heart rate at rest; and significant increase in both artificial right heart and natural left heart output and heart rates were observed during treadmill exercise, despite the marked decrease in left atrial pressure. The above results suggest that the increase in CVP and blood pressure in total artificial heart animals are not due to factors involving the artificial right heart, and that although left ventricular function acts in accordance with Starling's law at rest, this is no longer true during treadmill exercise.