Hisateru Takano

Impact of Systemic Depulsation on Tissue Perfusion and Sympathetic Nerve Activity

BACKGROUND We postulated that pathophysiologic processes under nonpulsatile circulation are related to the behavior of the sympathetic nerve activity that regulates tissue perfusion. METHODS Pulsatile and nonpulsatile pumps were installed in parallel in the left heart bypass circuit of anesthetized goats (n = 9) so that pulsatile circulation could be converted to nonpulsatile circulation instantly. At 5 minutes before and after systemic depulsation, we measured hemodynamic indices, renal nerve activity, and regional blood flow of the brain, heart, and renal cortex. RESULTS Renal nerve activity was significantly elevated after systemic depulsation (15.6 +/- 9.3 versus 19.4 +/- 9.8 microV), when mean aortic pressure remained almost constant. The renal cortical flow was significantly reduced after depulsation (3.61 +/- 1.23 versus 2.93 +/- 1.19 mL.min-1.g-1), whereas no significant difference was found in the regional blood flow of the brain or the heart. CONCLUSIONS The significant reduction of renal cortical blood flow after systemic depulsation is associated with a significant increase in renal nerve activity. Our results suggest that increased renal nerve activity plays an important role in the reduction of renal function after systemic depulsation.

Clinical Experience of Percutaneous Cardiopulmonary Support

Recently, percutaneous cardiopulmonary support (PCPS) combined with femoro-femoral bypass without reservoir has become valued because of its quick and easy application. We developed a fully preconnected compact integrated cardiopulmonary bypass (CPB) unit (priming volume of 250 ml) with a blind pore membrane oxygenator (Kuraray Menox) for PCPS. From 1990 to 1995, PCPS was performed in 49 patients of whom 26 were weaned from support. In most cases, we applied this CICU in patients with no active bleeding (22 patients); in patients with active bleeding (n = 13), we used Medtron-ics heparin-bonded close chest support pack (CCSP). Of these, PCPS was performed uneventfully for 2 h (median) in 8 elective cases; all of these patients were weaned or were switched to a left ventricular assist system (LVAS). In 8 urgent cases, such as those with low cardiac output syndrome, PCPS was performed for 4 days (median), 1 was weaned, and 2 CICU were cases switched to other procedures. In 32 cases of shock, 5 CICU patients were weaned, and 3 of them survived. Eight patients including 5 CICU patients and 1 CCSP patient were switched to operation or LVAS, and 2 CICU patients remain alive. From these data, PCPS has been shown to support the patients circulation in the acute phase and earn time to switch to operation or LVAS; the quick and easy set-up of the CICU can improve the clinical results. The use of the Medtronic device broadened the indication for PCPS. The CCSP enlarged the indication of PCPS but could not improve the results. To improve the results, a heparin-bonded surface is desired.

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.

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.

Hemodynamic effects of prostaglandins and catecholamines in graded reduction of pulmonary flow during venoarterial bypass in awake goats

The roles of prostaglandins and catecholamines in the hypotensive hemodynamic change during cardiopulmonary support with a venoarterial bypass (VAB) were investigated in a series of chronic animal experiments of gradually reduced pulmonary arterial blood flow (PAF). The VAB system consisted of a pulsatile ventricular assist device, an artificial lung, and the right atrium uptake and descending aorta return cannulae in four adult goats weighing 49-51 kg. The PAF was adjusted to 50, 10, and 0% of the total systemic blood flow. Indomethacin, an inhibitor of prostaglandin production; phentolamine, an alpha-antagonist of catecholamine; and noradrenaline, an agonist of catecholamine were administered at each PAF condition. The mean aortic pressure (mAoP) and the systemic vascular resistance decreased in proportion to the decrease in PAF. Indomethacin increased the mAoP at all PAF conditions, indicating a relationship between prostaglandins and hypotension. Phentolamine decreased the mAoP at all PAF conditions, indicating a normal response of catecholamine receptors. However, noradrenaline increased the mAoP at 50 and 10% PAF, but did not appreciably increase the value at 0% PAF, indicating complete response of catecholamine receptors to endogenous catecholamines at 0% PAF only. In conclusion, prostaglandins play a substantial role in hypotension during VAB, and catecholamines may subsequently increase in compensation for extreme hypotension.

Establishment of Flow Estimation for an Implantable Centrifugal Blood Pump

A less invasive and non thrombogenic flow estimation of an implantable centrifugal blood pump (ICBP) has been developed, which was derived from electric power consumption, the rotating speed of a motor, and blood viscosity presumed by hematocrit and body temperature. The power consumption and the rotating speed of the motor were measured by a wattmeter every 0.2 sec. Accuracy and stability of the estimated flow (EF) were investigated during in vitro and in vivo experiments. The EF was compared with a measured flow rate (MF) monitored by an electromagnetic flowmeter. During in vitro experiments, the EF and MF were measured at 79 operating points. The ICBP was driven in a closed mock loop filled with goat blood with hematocrit values of 21.5, 28, 34, and 42%. During in vivo experiments, the ICBP was implanted in the chest cavity of a goat and driven for 40 days

Importance of metabolic function of the natural lung evaluated by prolonged exclusion of the pulmonary circulation.

It is generally considered that the natural lung metabolizes various vasoactive substances through the pulmonary circulation. However, the influences of bypassing or eliminating the pulmonary circulation have not been fully elucidated, especially for prolonged periods. In this study, we performed total cardiopulmonary bypass and exclusion of the pulmonary circulation for up to 336 hr in awake goats to clarify the importance of the metabolic function of the lung. In seven adult goats, biventricular bypass with a pulsatile ventricular assist system was first established. After 2 weeks, the biventricular bypass was converted to total cardiopulmonary bypass without anesthesia. Adequate gas exchange and perfusion support were achieved in all animals. However, the institution of total cardiopulmonary bypass led to marked decreases in the mean aortic pressure and systemic vascular resistance, and they remained low thereafter. The arterial levels of prostaglandin E2 and norepinephrine, which are inactivated naturally through the pulmonary circulation, increased remarkably. These results indicate that the natural lung plays an important role in controlling systemic circulation by metabolizing various vasoactive substances. Understanding the non respiratory function of the natural lung is of prime importance for advancement of lung and heart-lung support.

Characteristics of Sympathetic Nerve Activity During Nonpulsatile Circulation

The autonomic nervous system plays an important role in circulatory control. However, the characteristics of sympathetic nerve activity (SNA) during nonpulsatile circulation, commonly applied to clinical cardiopulmonary bypass or circulatory assist, are not well understood. In this study, we examined the differences between renal SNA (RSNA) values in pulsatile and nonpulsatile systemic circulation in goats, whose heart rate and size are similar to those of humans. A 100% left heart bypass was instituted in two goats, weighing 60 and 66 kg, under general anesthesia. A pneumatic pulsatile pump and a centrifugal nonpulsatile pump were incorporated in parallel in the bypass circuit, so that the flow pattern was converted instantly. The pulse rate was set at 90 bpm during pulsatile circulation, irrespective of native heart rate, and the bypass flow rate was controlled to keep the mean aortic pressure constant. After depulsation, the pulse-synchronous discharges in RSNA disappeared and grouped discharges emerged irregularly instead, and mean RSNA increased. These results suggest that the vasotonus was changed by the loss of pulsatility in the systemic circulation during the immediate phase after depulsation.

Development of Centrifugal Pumps for Long-Term Circulatory Support

We have been developing centrifugal pumps for long-term use. The basic design of our pump series is a non-seal and no-shaft structure, with a central balancing hole made for continuous blood irrigation around the impeller. The first model, National Cardiovascular Center (NCVC)-0, had an impeller with four rectangular, curved vanes. To reduce the hemolysis rate, we employed six triangular curved vanes for the impeller in the second model, NCVC-1. To achieve further improvement in antithrombogenicity, in the third model, NCVC-2, the central hole was enlarged to enhance the blood-washing action. Six NCVC-0 and four NCVC-1 pumps were evaluated in long-term animal experiments; nine pumps were driven for more than 10 days, 3 were driven for more than 1 month, and one NCVC-1 pump ran for 80 days without anticoagulation. Three NCVC-2 pumps were driven without problems in 1-week experiments without antithrombotic therapy. The hemolysis indices were 0.05 g/1001, 0.01 g/1001, and 0.006 g/1001 in the NCVC-0, NCVC-1 and NCVC-2 pumps, respectively, while the mean value for the Biopump (BP-80; Bionediens, Prairie, MN, USA) was 0.008g/1001. An NCVC-1 pump was implanted inside the chest of a 52-kg goat as a left atrium-to-descending aorta bypass. These results suggest that our centrifugal pump could serve as an adequate circulatory support system for long-term usage.

Experimental Trial of Long-Term Heart and Lung Replacement

The feasibility of long-term total heart and lung replacement was investigated in a series of long-term animal experiments, in three adult goats and three calves. The animals’ natural heart and lungs were completely removed and replaced with an artificial heart-lung system that provided total support for both circulation and respiration. After the extirpation of the natural heart and lungs, the mean aortic pressure decreased significantly, from 96 ± 10 to 73 ± 19 mmHg. The level of prostaglandin E2, a hormone that is removed by the natural lung, increased markedly, from the pre-surgery level of 7 ± 5 pg/ml to 245 ± 273 pg/ml 2 h after the replacement. Renal dysfunction and systemic convulsions were observed in all animals, and none survived for more than 4 days postoperatively. The resection of the natural heart and lungs compromised not only the hemodynamic and metabolic condition but also major organ function, despite the well-maintained blood gas and cardiac output. Further investigation is necessary to completely elucidate the pathophysiology of total heart-lung replacement.