Kazuhiro Eya

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.

Baseline hemodynamic and echocardiographic indices in anesthetized calves.

The experimental calf model is used to assess mechanical circulatory support devices and prosthetic heart valves. Baseline indices of cardiac function have been established for the normal awake calf but not for the anesthetized calf. Therefore, we gathered hemodynamic and echocardiographic data from 16 healthy anesthetized calves (mean age, 189.0 ± 87.0 days; mean body weight, 106.9 ± 32.3 kg) by cardiac catheterization and noninvasive echocardiography, respectively. Baseline hemodynamic data included heart rate (65 ± 12 beats per minute), mean aortic pressure (113.5 ± 17.4 mm Hg), left ventricular end-diastolic pressure (16.3 ± 38.9 mm Hg), and mean pulmonary artery pressure (21.7 ± 8.3 mm Hg). Baseline two-dimensional echocardiographic data included left ventricular systolic dimension (3.5 ± 0.7 cm), left ventricular diastolic dimension (5.6 ± 0.8 cm), end-systolic intraventricular septal thickness (1.7 ± 0.2 cm), end-diastolic intraventricular septal thickness (1.2 ± 0.2 cm), ejection fraction (63 ± 10%), and fractional shortening (37 ± 10%). Doppler echocardiography revealed a maximum aortic valve velocity of 0.9 ± 0.5 m/s and a cardiac index of 3.7 ± 1.1 L/minute/m2. The collected baseline data will be useful in assessing prosthetic heart valves, cardiac assist pumps, new cannulation techniques, and robotics applications in the anesthetized calf model and in developing calf models of various cardiovascular diseases.

Development of a Centrifugal Pump with Improved Antithrombogenicity and Hemolytic Property for Chronic Circulatory Support

A centrifugal pump with a unique structure has been developed for chronic support. The pump is driven by a magnetic coupling and has no rotating shaft, no seal around the rotating part, and a balancing hole at the center of the impeller and the thrust bearing. The pump was improved in stepwise fashion to realize good antithrombogenicity and low hemolysis. The first pump, the National Cardiovascular Center (NCVC)-O, had an impeller with 4 rectangular and curved vanes; 6 triangularly shaped curved vanes were employed in the second model, the NCVC-1, to reduce trauma to the blood. In the third design, the NCVC-2, the central hole was enlarged, and the thrust bearing shoulder was rounded so that blood washing was enhanced around the impeller; stream lines also were smoothed for improved antithrombogenicity. The hemolytic property of the device was evaluated in vitro with heparinized fresh goat blood; hemolysis indexes of the NCVC-0, -1, and -2 were 0.05, 0.01, and 0.006 g per 100 L, respectively. Antithrombogenicity of the pumps was examined in animal experiments as a left heart bypass device in goats weighing 52-75 kg. Six NCVC-0 pumps were driven for 14 to 33 (22.0 ± 7.6) days in goats receiving the antiplatelet drug cilostazol orally. Four NCVC-I pumps ran for 1 to 80 (28.5 ± 30.6) days with the same drug regimen in 2 cases and with no anticoagulation therapy in 2 cases. After 3 preliminary 1-week tests of NCVC-2 pumps in animals, the pump was installed in 3 goats; 2 pumps were still running on the 182nd and 58th pumping day. Intracorporeal implantation also was attempted successfully. The results indicate that this pump has promising features for chronic support although longer term and additional evaluations are necessary.

Power of the fatigue resistant in situ latissimus dorsi muscle.

To evaluate the in situ latissimus dorsi muscle as an actuator for circulatory assistance, 1) muscle power was analyzed in animal experiments, and 2) muscle weight was measured in human cadavers. Three adult goats underwent 12 week preconditioning. The insertion of the latissimus dorsi muscle was then connected to a spring and a tension transducer in series. The stroke length was measured with a photosensor without power loss. With contraction of muscles under various loads, tension-length relationships at end contraction and end relaxation were obtained and the maximum area of a square drawn within both lines was assumed to be maximum external power. Good fatigue resistance and the highest maximum external power of 3.16 Watts/kg at 120 min was derived from preconditioned latissimus dorsi muscle in burst frequency of 50 Hz. Muscle weight in 42 human cadavers was negatively correlated with age (r = 0.56) and was expected to be 221.6 g in patients aged 45 years. According to these data, the power of a human preconditioned latissimus dorsi muscle was estimated as 0.7 Watts. It was concluded the power of in situ preconditioned latissimus dorsi muscles was appropriate for right heart assistance or counterpulsation for left heart assist.

Use of autologous auricular chondrocytes for lining artificial surfaces: a feasibility study

BACKGROUND Auricular elastic cartilage is a potential source of autologous cells for lining the luminal surfaces of cardiovascular prostheses. We tested this potential in vitro and in vivo using a left ventricular assist device (LVAD) and a calf model. METHODS In vitro, auricular cartilage was harvested from the anesthetized ear of a calf, isolated, and cultured on tissue culture dishes. Primary chondrocytes were typed by immunocytochemistry, transferred into culture media, passaged twice, and seeded onto the blood-contacting luminal surfaces of four LVADs (HeartMate; Thoratec Corporation, Woburn, MA). Seeded cell linings were preconditioned under simulated flow conditions to promote cell adhesion to luminal surfaces. Seeding efficiency and cumulative cell loss under flow conditions were quantitated. In vivo, one of the four autologous chondrocyte-lined and preconditioned LVADs was implanted into the tissue-donor calf; run for 7 days; explanted; and evaluated grossly, by scanning electron microscopy, and by transmission electron microscopy. RESULTS The efficiency of seeding chondrocytes onto the luminal surfaces of the four LVADs was 95.11% +/- 4.23% (n = 4). Cumulative cell loss during preconditioning under flow conditions in vitro did not exceed 12% (n = 4). After 7 days of in vivo implantation, the luminal surfaces of the implanted LVAD demonstrated an intact, strongly adherent cellular lining. CONCLUSIONS Auricular elastic cartilage is a ready and easily accessible source of chondrocytes whose ability to produce collagen II and other important extracellular matrix constituents allows them to adhere strongly to the luminal surfaces of LVADs. The simple method of isolating and expanding auricular chondrocytes presented here could be used to provide strongly adherent autologous cell linings for LVADs and other cardiovascular devices. If and when chondrocytes can be genetically engineered to produce antithrombogenic factors and then used to line the luminal surfaces of LVADs or other cardiovascular prostheses, they may be able to improve the hemocompatibility of the blood-biomaterial interface in such devices. Our successful feasibility study in a calf model warrants further studies of this concept in vivo.

Hemodynamic and Humoral Conditions in Stepwise Reduction of Pulmonary Blood Flow During Venoarterial Bypass in Awake Goats

The effects of reduced pulmonary arterial blood flow (PAF) during venoarterial bypass (VAB) on hemodynamic and humoral conditions were investigated in a series of experiments in a chronic animal model. A biventricular bypass system was installed in five adult goats weighing 49.8 ± 1.1 kg. Two weeks later, the extracorporeal circuitry was changed to VAB without anesthesia. The PAF was reduced stepwise from 100% to 50,25,10, and 0% of total systemic flow. The mean aortic pressure and systemic vascular resistance decreased from 110 ± 14 to 66 ± 3 mmHg and from 1,288 ± 77 to 740 ± 73 dyne-sec/cm5, respectively, in proportion to the decrease in PAF from 100 to 0%. The prostaglandin E2 con.

Influence of non pulsatile systemic circulation on tissue blood flow and oxygen metabolism.

Influence of non pulsatile systemic circulation on oxygen metabolism was examined regarding tissue perfusion in 12 adult goats weighing from 46 to 55 kg. Under general anesthesia, a flow character, changeable total left heart bypass circuit consisting of pulsatile and non pulsatile pumps was installed through a left thoracotomy. Systemic flow was converted from pulsatile to non pulsatile in 7 of 12 animals, and in the reverse order in the other 5, by changing the driving pump. Esophageal mucosal blood flow was determined by a colored microsphere method that estimated tissue blood flow at the pre capillary level. Esophageal intramucosal pH was evaluated with a silicone balloon tonometer catheter surgically placed in the submucosal space. Hemodynamic and arterial blood gas parameters were unchanged at flow mode conversion. Although oxygen delivery was comparable between pulsatile and non pulsatile circulation, oxygen extraction ratio was lower and venous oxygen saturation was higher in non pulsatile than pulsatile circulation. Although statistically not significant, serum lactate level tended to be higher with non pulsatile circulation. No difference was observed in esophageal mucosal blood flow between pulsatile and non pulsatile circulation, whereas intramucosal pH, which strongly correlated with arterial pH regardless of the flow mode, was significantly lower under non pulsatile than pulsatile conditions. In conclusion, systemic oxygen uptake is less efficient in non pulsatile than pulsatile circulation in the setting of an acute experiment using animals, which may be accounted for by the disparity between the pre capillary blood flow and actual tissue oxygen metabolism.

Heat Generation and Hemolysis at the Shaft Seal in Centrifugal Blood Pumps

The heat and hemolysis around a shaft seal were investigated. Materials were original pumps (Nikkiso HMS-15:N-original, and 3M Delphin:D-original), vane-removed pumps (Nvane(-), Dvane(-)), and a small chamber with a shaft coiled by nichrome wire (mock pump). The original pumps were driven at 500 mmHg and 5 L/min, and vane-removed pumps were driven at the same rotation number. An electrical powers of 0, 0.5, 2, and 10 W was supplied to the mock pumps. In vitro hemolytic testing showed that hemolytic indices were 0.027 g/100 L in N-original, 0.013 in Nvane(-), 0.061 in D-original, and 0.012 in Dvane(-). Measurement of heat with a thermally insulated water chamber showed total heat within the pump of 8.62 and 10.85 W, and heat at the shaft seal of 0.87 and 0.62 W in the Nikkiso and Delphin pumps, respectively. Hemolysis and heat generation of mock pumps remained low. The results indicate that the heat generated around the shaft seal was minimal. Hemolysis at the shaft-seal was considerable but not major. Local heat did not affect hemolysis. It was concluded that the shaft-seal affected hemolysis, not by local heat but friction itself.

Preclinical assessment of a trileaflet mechanical valve in the mitral position in a calf model.

BACKGROUND The bileaflet valve is currently the mechanical replacement valve of choice. Though durable, it does not closely mimic native valve hemodynamics and remains potentially thrombogenic. METHODS Prototype trileaflet valves (T1 and T2) were implanted in the mitral position in calves. Group I calves received either a T1 valve (n = 12) or a control bileaflet valve (n = 5); Group II, either a T2 valve (n = 7) or a control bileaflet valve (n = 5). Valve function, perivalvular leakage, and transvalvular pressure gradients were evaluated. Also, long-term prototype leaflet wear was evaluated in vivo in one Group I calf (502 days) and two Group II calves (385 and 366 days). Calves were euthanized and necropsied at study termination, and major organs weighed and examined. RESULTS Valve function was excellent and hematologic parameters remained normal in all calves that survived to study termination. Mean peak transvalvular pressure gradients were 10 +/- 7 mm Hg for T1 valves, 6 +/- 3 mm Hg for T2 valves, and 12 +/- 4 mm Hg for bileaflet control valves. Clinically insignificant valvular regurgitation was observed in both prototypes. Explanted valves showed no thrombus-impaired leaflet motion, except in two T1-fitted calves and one T2-fitted calf. Major organs showed no evidence of clinically significant thromboembolic events. There were no other significant differences between the results of experimental and control groups. CONCLUSIONS Prototype trileaflet valves performed safely and effectively in the mitral position in calves, even without long-term anticoagulation. This warrants their evaluation as an equivalent alternative to bileaflet valves.

Set-up, improvement, and evaluation of an electrohydraulic total artificial heart with a separately placed energy converter.

The authors have been developing an electrohydraulic total artificial heart (TAH) system with a separately placed electrohydraulic energy converter to minimize anatomic constraints in the pericardial space. Improvements to the system and current status of the development are reported. The energy converter was miniaturized to improve implantability, and its thickness was reduced to 54 mm. System efficiency was increased by suppressing rush current at the time of motor reversal. Maximum cardiac output of the TAH system was 9 L/min, and maximum system efficiency increased to 10%. The blood pump system was implanted easily in the body of a 57 kg calf, and no significant temperature rise on the energy converter surface was observed. As the next step, main components were integrated into a total system. The transcutaneous energy transfer system could supply power to the TAH without a decline in pump performance, and the internal battery could support the system at 6.5 L/min of cardiac output for 1 hour without a decrease in cardiac output. The authors consider the TAH system with a separately placed energy converter the most promising approach to development of a TAH for smaller sized patients.