Y. Baba

Acute Phase Responses of Vasoactive Hormones to Non Pulsatile Systemic Circulation

Acute phase responses of vasoactive hormones to the rapid conversion of a systemic flow pattern from pulsatile or non pulsatile mode to the reverse were assessed in 20 goats weighing 45-69 kg. A total left heart bypass was instituted under general anesthesia, with pulsatile and non pulsatile pumps interposed in the circuit in parallel, and the systemic flow mode was rapidly and bidirectionally converted from the pulsatile mode or non pulsatile mode to the reverse. Vasoactive hormone levels and hemodynamics were evaluated before and after 5 min of conversion. No significant difference was observed between the modes either in blood flow or systemic vascular resistance, while the mean aortic pressure was significantly higher in the non pulsatile mode than the pulsatile mode (106.7 +/- 2.4 versus 99.9 +/- 3.5 mmHg). Among various vasoactive hormone levels evaluated, only norepinephrine showed a significant difference between the modes, where concentration in the non pulsatile mode was significantly higher than the pulsatile mode (391.0 +/- 60.7 versus 309.4 +/- 42.5 pg/ml). No correlation was found between the absolute values of mean aortic pressure and norepinephrine level, whereas a significant reciprocal correlation was detected between the magnitude of inter-mode differences in these two parameters. In conclusion, a non pulsatile systemic circulation does not exert significant influence on vasoactive hormone levels, except for slight increase in norepinephrine with a reciprocally correlated increase in mean aortic pressure. It is deduced that activity of the sympathetic nervous system represented by norepinephrine level is higher in the non pulsatile mode than the pulsatile mode, and the baroreceptor reflex functions in an acute phase after flow mode conversion.

An approach to reducing hemolysis in an axial-flow blood pump.

In an attempt to decrease hemolysis caused by an axial-flow blood pump, we studied whether specific speed (Ns) at a design point (determined by flow in m3/min, pump head in m, and pump speeds in rpm), should be kept within the existing engineering standard range (1000 < Ns < 2500) or whether pump speed should be reduced to a minimum (Ns < 1000). Four pumps (A: 14,000 rpm, B: 18,000 rpm, C: 22,000 rpm, and D: 26,000 rpm), each with an impeller 11.8 mm in diameter, were designed to accommodate a flow rate of 5 L/min and a pressure head of 100 mmHg. At this design point, the Ns of each pump was calculated as A:758, B:974, C:1191, and D:1407. Pump performance was observed, and the total efficiency of each pump was calculated. The hemolysis index (HI) was calculated after simultaneous testing in duplicate of all four pumps using fresh goat blood (anticoagulated with citrate-dextrose solution) in a closed mock-loop circuit. Total efficiency of each pump was calculated as A:49%, B:50%, C:45%, and D:22%. In the first hemolytic test, HIs were measured as A:0.066, B:0.18, and C:0.13; a water seal failed in pump D. In the second test, HIs were B:0.077, C:0.0499, and D:0.12; a bearing failed in pump A. It is concluded that a lower level of hemolysis is associated with a pump speed in the minimum range at the design point, even though Ns is outside the standard range.

Improvement in antithrombogenicity in a centrifugal pump with self wash-out structure for long-term use.

Antithrombogenicity in the initial (NCVC-1) centrifugal pump (CP) developed at our institute is provided by a central balancing hole in an impeller that promotes self wash-out blood flow (Sf) around the impeller. The current CP (NCVC-2) was ameliorated to obtain better antithrombogenicity, where the balancing hole diameter was widened to improve Sf velocity (Vsf), and the edge of a thrust bearing (TB) was rounded to minimize flow separation. Effects of the modifications were assessed in in vitro and in vivo studies. The Vsf of the NCVC-1 and the NCVC-2 evaluated by Doppler velocimeter were 12.8 and 22.1 cm/sec, respectively. Flow around the TB visualized by a light cutting method confirmed less flow stagnation in the NCVC-2. In vivo antithrombogenicity of the CPs was investigated in three goats. A pulsatile VAD (P-VAD) was installed paracorporeally between the left atrium and the aorta. After 3 weeks, the P-VAD was exchanged for the NCVC-2 and the NCVC-1 in sequence. Each CP was driven for 1 week and disassembled. No anticoagulation was used, except for heparin injection at pump exchange. Thrombus at the TB was found in the two NCVC-1s, and two little thrombi were on the impeller of another NCVC-1, whereas a thrombus smaller than 1 mm3 at the TB was noted in one NCVC-2. These results indicate that the NCVC-2 has better antithrombogenicity and Sf around the impeller and the TB.

Development and evaluation of components for a totally implantable artificial heart system.

The authors have been developing an electrohydraulic (EH) artificial heart system for total implantation. This system consists of intrathoracic ventricles, an abdominally placed EH actuator, flexible silicone oil conduits, externally coupled transcutaneous energy transfer (TET) system, transcutaneous optical telemetry (TOT) system, internal battery, and internal control drive unit. Fitting was evaluated in chronic animal experiments as a pneumatic system in 11 goats weighing 55.2 +/- 4.2 kg and 3 calves of 52.3 +/- 1.2 kg. The longest survival time in calves was 111 days, and that in goats was 51 days. The assembled EH pump was implanted in two goats of 49 and 50 kg as an acute experiment, and 4.2-6.7 L/min of cardiac output was maintained. For the TET system, an internal coil 3 cm in diameter was implanted to make an arch covered by skin. Electric energy was transmitted from the external to the internal coil, and energy of about 20 W was carried through wires to an external load. The DC-to-DC efficiency of the system was 76-83% for 40 days. The TOT system with internal light emitting diodes and external photodiodes also was evaluated in a goat. Disalignment of up to 12 mm was tolerated. Although more improvement is necessary, most of the components showed characteristics desirable for a totally implantable system.

Influence of an impeller centrifugal pump on blood components in chronic animal experiments

A chronic animal experiment was designed to examine the changes in blood components induced by the use of a centrifugal pump (CP). In the pump, an impeller spins in a blood chamber by magnetic coupling with a rotating magnet outside the blood chamber. A pulsatile ventricular assist device was implanted between the left atrium and the descending aorta in four goats weighing from 63 to 75 kg; the CP was installed to replace the assist device, without surgery and anesthesia, more than 2 weeks later when the influences of implantation surgery were diminished. Antithrombotic therapy was performed with oral administration of an antiplatelet agent, cilostazol, a cyclic adenosine monophosphate phosphodiesterase at a dose of 30 mg/kg/day. No significant differences were observed in any of the following parameters: 1) hematocrit, 2) plasma free hemoglobin, 3) lactic acid dehydrogenase, 4) adenosine diphosphate, 5) platelet count, 6) fibrinogen, and 7) antithrombin III, between the data before and after the use of the CP, nor were deformation or pseudopods of platelets seen. The CP developed in the authors institute and evaluated in this study did not damage blood components, and it proved to be a promising device for long-term use.

Development of an electrohydraulic total artificial heart at the National Cardiovascular Center, Osaka, Japan.

The authors have been developing an electrohydraulic total artificial heart with a basic concept placing the blood pumps and an electrohydraulic energy converter separately, in the thorax and the abdominal region, respectively, to minimize anatomic constraints. Major problems of the system were a high energy consumption of 56 W at 6 L/min output and an insufficient maximum output of 6.7 L/min. The energy converter was redesigned to overcome these problems. A three phase, 4 pole brushless DC motor, which has maximum efficiency of 79% at a motor rotation of 2500 rpm with a load of 0.1 Nm, was developed for the new energy converter. Flow-channel design of the regenerative oil pump was optimized, which resulted in increasing the maximum flow rate at one directional motor rotation from 18 to 29 L/min. In vitro performance of the electrohydraulic total artificial heart was evaluated in a mock circulation with physiologic pressure conditions. Maximum output was increased to 10.7 L/min at a pump rate of 120 bpm and energy consumption of the motor at 6 L/min output was reduced to 18 W. Based upon these favorable results, the system is now being assembled for chronic animal implantation.

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 Two Stage Axial Flow Pump: New Approach to Reduction of Hemolysis

From an engineering point of view, the suitable revolution number for high efficiency operation of an axial flow pump is known. A multistage axial flow pump is a useful tool for reducing revolution number with a high efficiency axial flow pump. A two stage (25) axial flow pump designed at a 5 L/min flow rate and a 100 mmHg pressure head was evaluated in three kinds of in vitro hemolysis tests. Each stage design point of the 2s pump was tested at a 5 L/min flow rate and a 50 mmHg pressure head. Specific speed and revolution number of the 2S pump were 1400 rpm, m3/min, m, and 15500 rpm, respectively. In the first test the 2S pump was compared with two single stage axial flow pumps (1S-A and 1S-B100) designed by the same method. The specific speed of the 1A was the same as that of the 2S pump, which was driven at 26000 rpm. The impeller of the 1S-B100 was the same as that of the 2S pump, which was driven at a 22000 rpm RN and a 1100 specific speed. The 2S pump was separated into two single stage axial flow pumps and the effect of series operation on hemolysis was evaluated in the second test. In the third test the 2S pump was compared with the 1S-B100 by using diluted goat blood samples with three different hematocrit values. The results showed that the hemolysis index of the 2S pump, regarded as a total hemolysis index of both stage axial flow pumps, was less than those of the single stage axial flow pumps at all hematocrit values.

Tandem Operation of a Turbo Blood Pump (BP‐80‐Type Centrifugal Pump) to Reduce Hemolysis

When operating turbo blood pumps in tandem, the strength of shear stress is reduced, but the exposure duration of the stress is increased. The purpose of this experiment was to compare the degree of contribution of these two factors on hemolysis as well as to evaluate the effectiveness of the tandem operation of turbo blood pumps. Tandem operation of two Bio-pumps (BP-80; Medtronics Bio-medicus, Inc., Eden Prairie, Minnesota, U.S.A.) were compared with single operation of a BP-80 in in vitro hemolysis tests in three different driving conditions, that is, pumping heads of 200, 350, and 500 mm Hg under a pump flow rate of 5 L/min. The Allens hemolytic indexes of the tandem operation at pumping heads of 200, 350, and 500 mm Hg were 0.014, 0.020, and 0.080 mg/dl, respectively. The hemolytic indexes of the single operation at pumping heads of 200, 350, and 500 mm Hg were 0.014, 0.056, and 0.12 mg/dl, respectively. These results indicate that tandem operation is a useful method of reducing hemolysis with the BP-80 under high pumping heads and that the effect on hemolysis of exposure to higher shear stresses may be more serious than that of longer durations of exposure to shear stress in turbo blood pumps.

A bioartificial ventricle used as a totally implantable circulatory assist device.

The authors designed a totally implantable circulatory assist device consisting of a bioartificial ventricle composed of a skeletal muscle ventricle lined with a bioartificial endocardium. The bioartificial endocardium consists of a structural matrix made of a polyurethane porous membrane, fragmented blood vessels, and collagen gel. The authors prepared the polyurethane porous membrane by solvent cocasting with salt powder. They used collagen gel with fragmented goat carotid vein to perform in vitro construction of the bioartificial endocardium. For in vivo construction of the bioartificial endocardium, the authors used a modified version of the tissue fragment method for vascular prostheses. The authors prepared suspensions of tissue fragments using collagen gel with fragmented goat carotid artery. They used a highly porous fabric vascular prosthesis as a structural matrix; tissue fragments were entrapped on the outer surface of the prosthesis, and the prosthesis then was implanted into the carotid artery of four adult goats. In specimens 1 and 3 months postimplantation, cells from the fragmented tissue regenerated an endothelium-like monolayer sheet on the inner surface of the prostheses. Output of a prototype bioartificial ventricle reached 660 ml/min at an afterload of 60 mmHg and a preload of 20 mmHg. Based on these data, the authors conclude that the bioartificial ventricle is promising as an implantable device with excellent antithrombogenicity.