Activated leukocytes and oxygen free radicals have been implicated in the pathogenesis of heart and lung injury after reperfusion and during cardiopulmonary bypass (CPB). This study is to determine whether leukocyte depletion prevents injury to the heart and lung during CPB. [Patients and Methods] Twenty-eight patients underwent open heart surgery in this study. In Group F, leukocyte depletion was performed with a LG 6 arterial line filter following the aortic declamping (n=14) . Leukocyte depletion was not achieved in Group C as a control. Thereafter, cardiac and lung function were assessed for 24 h after the reperfusion. [Results] The total catecholamine dose used for 24h after reperfusion (r) was 61.9±13.4 in Group C and 43.9±19.2 in Group F (p<0.05). CK-MB at 3 and 6h after the reperfusion was 65.9±13.5 and 64.8±15.8 in Group C and 55±11.8, 54±11 in Group F (NS). The pulmonary index after reperfusion at 3 and 6 h was 1.7±0.5, 1.3±0.4 in Group C and 0.7±0.3, 0.6±0.4 in Group F, respectively (p<0.05). The lung function in Group F was significantly better preserved. Therefore, leukocyte depletion was significantly effective in preserving lung function after the reperfusion.

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To reduce hemolysis in an axial flow pump (AP), a basic study of a two stage AP (2S) was performed. The 2S was evaluated in two kinds of in vitro hemolysis tests for four hours. In the first test, the 2S was compared with two kinds of single stage APs (1Ss). Each pump was designed to be operated at a flow rate of 5l/min and a pressure head of 100mmHg. The 2S was series operation of two single stage APs designed at a flow rate of 5l/min and a pressure head of 50mmHg. One of the 1Ss has the same specific speed (Ns) of the 2S and the other 1S has the same impeller of the single stage of the 2S. In the second test, hemolysis in each stage of the 2S was evaluated. The basic structure of all single stage APs were same. Allen's hemolytic Index (HI) of the 2S, that was regarded as an aggregate HI of both stage AP, was less than those of the iSs. These data suggests that the 2S was useful to reduse hemolysis in an AP.

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We described a bioartificial endocrine pancreas (Bio-AEP) which was constracted by placing pancreatic B-cell clusters (ICCs) trapped in a mixed matrix (mixture of extracellular matrix and agarose, containing maltose-carrying polystyrene and nicotinamide) in the center of a ring holder sandwiched between semipermeable membranes, which were shielded by silicone. In this experiment, nuclepore membranes of different pore size (0.2, 0.1, or 0.05μm), were employed as the semipermeable membrane, which provided a mechanical barrier between the endocrine pancreatic graft and the host's immune system. Streptozotocin (STZ)-induced diabetic rats were implanted with BioAEP containing mouse insulinoma B-cell (MINE-cells) clusters which respond to glucose stimulation. In STZ-diabetic rats with Bio-AEPs with a membrane of pore size 0.1μm, a return to normoglycemia was observed up to 20 weeks after implantation, without the use of any immunosuppressant. STZ-diabetic rats that had received Bio-AEPs with membranes of different pore sizes, did not remain normoglycemie for such a long period. The result indicate that the Bio-AEP with the 0.1μm pore size membrane should be useful for the implantation of xenograft pancreatic endocrine cells in diabetic animals and may open a new field in the therapy of human insulin-depended diabete mellitus.

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A nonlinear mathematical technique was utilized to analyze the cardiovascular regulatory system including ventricular assist system (VAS) in various pumping mode. During synchronous mode left ventricular assistance, chaotic attractors of the arterial blood pressures were evident in the phase space. A nonstructured pattern was observed during internal mode left ventricular assistance. These results suggest that the cardiovascular control system with VAS synchronous mode assistance may be a higher order system than the natural heart system; this is in turn suggests that the dynamics are compatible with deterministic chaos.

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We evaluated performance of an axial flow pump, which was newly developed as an implantable left ventricular assist system for long-term support, with chronic animal experiments using calves. This pump weighted 85g and had a displacement volume of 25ml. The pump output of 2-10l/mmn was obtained at 6-10 Watts of power in a mock circulation system. We had implanted the pump to three calves for chronic animal experiments. Implantation of the pump were done easily and safely without a cardio-pulmonary bypass. Three calves survived for 70, 120 and 155 days, respectively. The pump flow were maintained from 5 to 6 l/min and the plasma free hemoglobin ranged 2.0 to 10.0mg/dl during support. These animal experiments were terminated due to accidental disconnection of electrical wire cable and seizure of the impeller. These results shows that the Jarvik 2000^TM system had acceptable pump performance without hemolysis and it might be applicable for long term circulatory assist even for smaller patients including children.

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Using a hybrid artificial lung model including hollow fibers with micropores and cell adhesion onto the membrane, the effect of cell adhesion on oxygen transfer rate was estimated. Positive charge with DEA group to a hydrophillic hollow fiber apparently increased the attached cell density and that was almost same as that of a collagen coated fiber. The cell growth rate on the charged fiber was comparable with that in a culture dish. The oxygen transfer rate using the cell free hollow fiber module increased with increase of gas flow rate suggesting decrease of liquid leakage. The oxygen permeability coefficient in the membrane was determined to 1.0 x 10^-2cm/min from the Wilson's plot, which was lower than that of conventional artificial lungs. Cell attachment in the module increased the membrane permeability coefficient to 2.98 x 10^-2cm/min. However, an analysis using dimensionless numbers of Sherwood and Schmidt number revealed that the cell adhesion did not cause apparent change of the mass transfer coefficient of liquid thin layer. These results shows the possibility that the micropore hollow fiber membrane having cell layer can achieve proper oxygen transfer rate and also that it can avoid blood leakage across the membrane. This may promise a hybrid artificial lung for clinical application.

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As circulatory assist, the latissimus dorsi muscle (LDM) is used with two different stimulation modes, i. e. co- or counter-pulsatile stimulation. Thoracodorsal arterial flow (TDF) profile and vascular resistance of the thoracodorsal artery (R) may differ in these two different stimulation modes, and influences to LDM work is still unknown. We evaluated TDF, R, internal pressure (P) and power (Pw) of the unconditioned swine LDM between co-and counter-pulsatile stimulation. During co- and counter-pulsatile stimulation, TDF profile predominated in cardiac diastolic and cardiac systolic period, respectively. For contracting period of the LDM, 1/R was almost constant when P was below 50mmHg. And negative correlation between P and 1/R was observed when P was over 50mmHg. In mean TDF, Pw, and relationship between P and 1/R, there was no difference between two stimulating patterns. These results suggested that relaxing period of the LDM is important for blood supplies to the LDM and these two stimulating patterns may cause no difference in mean TDF, LDM work and influence of P to R.

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We performed a comparative study to evaluate effects of pulsatile and nonpulsatile circulation on renal and skin microcirculation after cardiogenic shock in pigs. Cardiogenic shock model was made by ligating the left anterior descending branch. After fibrillation, biventricular assist devise were initiated. In pulsatile circulation group (Group P: 5 cases), Nippon Zeon pneumatic VAD was used for left heart, while Nikkiso centrifugal Pump HPM-15 for right heart. In nonpulsatile circulation group (Group NP: 5 cases), both left and right heart were supported by Nikkiso centrifugal pump HPM-15. Renal cortical blood flow and skin blood flow showed significantly higher in Group P than Group NP. Renal cortical blood flow/renal (cortex+medulla) blood flow also demonstrated improvement tendency in Group P compared with Group NP. LIP ratio was increased after 2h assist in Group P. These results suggest that a certain pulsetility may be necessary to maintain microcirculation and function of kidney after cardiogenic shock.

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A volume sensor, consisting of three sets of laser photoelectric sensors and a microcomputer, monitors the amount of blood in a flexible reservoir. The laser sensors attached to both sides of the vinyl reservoir, detect the widths of the reservoir at three points. The blood volume in the reservoir was calculated from calibration curves. The calculated volume showed correlation with real volume (r²>0.98) and the accuracy of the measurements were within ±47ml (M type) and within ±22ml (S type). The sensor could detect both transparent and opaque liquids.

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We report clinical experiences with using heparin-coated PCPS system consisted of 4.8m² hollow fiber membrane oxygenator, a centrifugal pump, and percutaneous cannlae. All surfaces in contact with blood are treated with a covalently bonded heparin developed by Terumo inc.. This system was used for femoral veno-arterial bypass under low systemic heparinization in 3 patients (pts) with descending thoracic aortic aneurysm and one pt with dilated cardiomyopathy for emergent circulatory support. Anti-thrombogenesity was evaluated by changes in the activities of platelet, coagulation and fibrinolysis during bypass. Blood contacting surfaces after bypass were studied by scanning electron microscope. In the pts with descending thoracic aortic aneurysm, this system did not have any problems in antithrombogenesity under minimal administration of heparin. However, in a pt with cardiomyopathy, major thrombi were noted in the oxygenator in spite of maintaining 200 to 300 seconds in ACT. In this pt, both coagulation and fibrinolysis were remarkably activated before bypass. It is suggested that this heparin-coated system seems to have satisfactory anti-thrombogenesity even in minimal administration of heparin in the clinical setting. Further investigation seems necessary when the patient is under the special pathologies in coagulation disorders.

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