Kin-ichi Nakata

The Role of Pulsatility in End-Organ Microcirculation After Cardiogenic Shock

To estimate the effectiveness of pulsatility in end-organ microcirculation after cardiogenic shock, experimental studies using swine were done. Cardiogenic shock was produced in 14 pigs by ligating the left anterior descending branches so that mean aortic pressure dropped to 60% of the control value. After inducing shock, left atrial to ascending Ao bypass was initiated. A pneumatic pulsatile pump (Zeon Medical Inc, Tokyo, Japan) was used in seven pigs (Group P) and a centrifugal pump (BP-80, BioMedicus Inc, Minneapolis, MN) in seven (Group NP). In both groups, about half the usual cardiac output was supported for 3 hr, maintaining mean aortic pressure at approximately 100 mm Hg. The pulse pressure was 36.6 +/- 4.6 mm Hg in Group P, and 14.3 +/- 1.5 mm Hg in Group NP. Epicardial and endocardial regional flows recovered after assist in both groups. There were no significant differences between the two groups. However, liver tissue flow, renal cortex flow, and stomach mucous flow in Group P was significantly higher than those of Group NP after support (p < 0.05). In addition, arterial blood ketone ratio in Group P was 0.61 +/- 0.13 vs 0.39 +/- 0.06 in Group NP, a significant difference (p < 0.05). These results suggest that in uneven blood flow distribution of end organs after cardiogenic shock, pulsatility was effective in improving and maintaining function and microcirculation of end organs, preventing multiorgan failure.

Effect of pulsatile and nonpulsatile assist on heart and kidney microcirculation with cardiogenic shock.

To estimate microcirculation of the heart and kidney in pulsatile and nonpulsatile-assisted circulation, a comparison study was done using a swine model. Acute myocardial infarction was made by ligation of the left coronary artery branches. After cardiogenic shock, animals were divided into 3 groups as follows: Group C (n = 6), no assist provided; Group NP (n = 6), assisted by a nonpulsatile pump (Bio-Medicus BP-80); Group P (n = 6), supported by a pulsatile pump (Nippon Zeon). Left coronary artery flow, endocardial and epicardial regional flows, and renal cortex and medulla tissue blood flows were measured. Left coronary artery flow and endocardial and epicardial tissue blood flows decreased in cardiogenic shock, and they recovered to the control level soon after support in both Group N and Group P. Renal medulla and cortex tissue blood flows decreased in cardiogenic shock, and these flows did not recover in either Group N or P. However, cortex blood flow in Group P did improve, but it did not improve in Group N. These results suggested that pulsatile assist was more effective than nonpulsatile assist for microcirculation after cardiogenic shock to avoid deterioration of major organ functions.

Development of a totally implantable biventricular bypass centrifugal blood pump system

BACKGROUND During the past 2 years, the development of a totally implantable biventricular bypass rotary blood pump system has been made. METHODS An extracorporeal gyro centrifugal pump, the CIE3, was miniaturized and developed into the PI601, a totally implantable plastic pump. Two-day anatomic and hemodynamic feasibility studies demonstrated that these two pump systems were easily implantable inside a calfs abdominal wall, directly under the diaphragm. The priming volume of the pump was 20 mL, with sufficient cardiac outputs at approximately 2,000 rpm and requiring less than 10 W of power. Two-week antithrombogenic screening tests also revealed these pump systems to be quite antithrombogenic. In addition, 1-month system reliability studies demonstrated fail-safe reliable performances. RESULTS AND CONCLUSIONS Encouraged by these preliminary studies, the PI601 model was converted to the permanently implantable titanium gyro pump PI702 model. The long-term implantations were initiated approximately 3 months ago, and two such long-term LVAD studies are currently underway with no sign of difficulty (October 10, 1997). They were followed 283 days and 72 days, respectively. Both terminated due to functional inflow obstruction. There were no blood clots or emboli at autopsy.

Comparison of febuxostat and allopurinol for hyperuricemia in cardiac surgery patients with chronic kidney disease (NU-FLASH trial for CKD)

BACKGROUND The NU-FLASH trial demonstrated that febuxostat was more effective for hyperuricemia than allopurinol. This time, we compared these medications in patients with chronic kidney disease (CKD) from the NU-FLASH trial. METHODS AND RESULTS In the NU-FLASH trial, 141 cardiac surgery patients with hyperuricemia were randomized to a febuxostat group or an allopurinol group. This study analyzed 109 patients with an estimated glomerular filtration rate (eGFR) ≤60 mL/min/1.73 m(2), and also analyzed 87 patients with stage 3 CKD. The primary endpoint was the serum uric acid level. Secondary endpoints included serum creatinine, urinary albumin, cystatin-C, oxidized low-density lipoprotein, eicosapentaenoic acid/arachidonic acid ratio, total cholesterol, triglycerides, low-density lipoprotein, high-density lipoprotein, and high-sensitivity C-reactive protein. Among patients with an eGFR≤60 mL/min/1.73 m(2), uric acid levels were significantly lower in the febuxostat group than the allopurinol group from 1 month of treatment onward. The serum creatinine, urinary albumin, cystatin-C, oxidized low-density lipoprotein, eicosapentaenoic acid/arachidonic acid ratio, and high-sensitivity C-reactive protein were also significantly lower in the febuxostat group. Similar results were obtained in the patients with stage 3 CKD. CONCLUSION In cardiac surgery patients with renal dysfunction, febuxostat reduced uric acid earlier than allopurinol, had a stronger renoprotective effect than allopurinol, and also had superior antioxidant and anti-inflammatory effects.

Preclinical evaluation of a hollow fiber silicone membrane oxygenator for extracorporeal membrane oxygenator application.

A silicone membrane hollow fiber oxygenator applicable for use as an extracorporeal membrane oxygenator (ECMO) has been developed in our laboratory. This silicone hollow fiber displays astonishing mechanical stability, is barely compressible or stretchable, and assembles easily while maintaining good gas permeability. The priming volume is 140 cc with a surface area of 0.8 m2. This study evaluated the gas transfer performances and biocompatibility of the oxygenator under ECMO and CPB conditions. In vitro studies that were performed at a blood flow rate of 2 L/min, and revealed O2 and CO2 gas transfer rates of 82.35 ± 0.56 ml/m2/L/min and 38.72 ± 2.88 ml/m2/L/min, respectively. The commercially available Kolobow (Avecor 1500) oxygenator was used as the control, and had O2 and CO2 gas transfer rates of 53.8 ± 0.5 ml/m2/L/min and 24.7 ± 2.0 ml/m2/L/min. To evaluate blood trauma, Normalized Index of Hemolysis (NIH) was measured according to American Society of Testing and Materials (ASTM) standards. The NIH findings were 0.0112 g/100L at a blood flow of 1 L/min, and 0.0152 g/100L at 5 L/min. Three ex vivo experiments, using a blood flow rate of 1 L/min, were performed with venoarterial bypass, and O2 transfer rate and CO2 transfer rate of the oxygenators were well maintained. This indicates that this preclinical silicone membrane hollow fiber oxygenator has superior efficiency, less blood trauma, and is smaller when compared with the only clinically available Kolobow oxygenator.

Results of low-dose carperitide infusion in high-risk patients undergoing coronary artery bypass grafting.

BACKGROUND This study investigated the efficacy of human atrial natriuretic peptide (hANP, carperitide) for high-risk patients undergoing coronary artery bypass grafting (CABG). METHODS This was a randomized controlled trial of 367 high-risk patients (European System for Cardiac Operative Risk Evaluation above 6) undergoing CABG. The primary endpoint was major adverse cardiovascular and cerebrovascular events (MACCE). Secondary endpoints were (1) postoperative death, (2) MACCE + hemodialysis, and (3) serum creatinine and brain natriuretic peptide (BNP) levels. Logistic regression analysis was conducted to identify preoperative and perioperative factors related to early death and MACCE. RESULTS There was no significant difference of survival between the hANP and placebo groups (p = 0.1651), but the MACCE-free rate was significantly higher in the hANP group than in the placebo group (p < 0.0001). No patient from the hANP group started hemodialysis after operation, but 7 patients did in the placebo group, and the dialysis rate was significantly lower in the hANP group (p = 0.0147). Serum creatinine and BNP were also significantly lower in the hANP group at 1 year postoperatively. MACCE were strongly associated with age 75 years or older, chronic kidney disease, hemodialysis, left ventricular dysfunction, and nonuse of carperitide. CONCLUSIONS In the early postoperative period, carperitide has a cardiorenal protective effect that prevents postoperative MACCE and hemodialysis. Perioperative low-dose carperitide infusion may be useful in high-risk patients undergoing on-pump CABG.

LONG-TERM IN VIVO LEFT VENTRICULAR ASSIST DEVICE STUDY WITH A TITANIUM CENTRIFUGAL PUMP

A totally implantable centrifugal artificial heart has been developed. The plastic prototype, Gyro PI 601, passed 2 day hemodynamic tests as a functional total artificial heart, 2 week screening tests for antithrombogenicity, and 1 month system feasibility. Based on these results, a metallic prototype, Gyro PI 702, was subjected to in vivo left ventricular assist device (LVAD) studies. The pump system employed the Gyro PI 702, which has the same inner dimensions and the same characteristics as the Gyro PI 601, including an eccentric inlet port, a double pivot bearing system, and a magnet coupling system. The PI 702 is driven with the Vienna DC brushless motor actuator. For the in vivo LVAD study, the pump actuator package was implanted in the preperitoneal space in two calves, from the left ventricular apex to the descending aorta. Case 1 achieved greater than 9 month survival without any complications, at an average flow rate of 6.6 L/min with 10.2 W input power. Case 2 was killed early due to the excessive growth of the calf, which caused functional obstruction of the inlet port. There was no blood clot inside the pump. During these periods, neither case exhibited any physiologic abnormalities. The PI 702 pump gives excellent results as a long-term implantable LVAD.

Development of an antithrombogenic and antitraumatic blood pump: the Gyro C1E3.

The Gyro C1E3 is a centrifugal blood pump. Its antithrombogenic and antitraumatic blood features were demonstrated by prior studies. Based upon these studies, a mass production model of the C1E3 is becoming commercially available. Therefore, this feasibility study was conducted using the mass production models of the Gyro C1E3 for long-term cardiac assist in ex vivo animal experiments. Five healthy calves were used and 15 pump heads were applied for different time periods (Group 1, 30 days; Group 2, 14 days; Group 3, 10 and 7 days; Group 4, 4 days; and Group 5, 2 days). Activated clotting time (ACT) was kept at 200-250 sec. All five calves demonstrated neither abnormal signs nor abnormal blood examination data throughout the experiment. During necropsy, no thromboembolism was found in any downstream organs. Groups 1-4 showed thrombi inside the pump heads while two pumps in Group 5 had no thrombi formations. Bearing deformation or possible wear did not increase after 2 days of pumping. The C1E3 is capable of long-term assist circulation. However, after 2 days of pumping, careful observation is necessary since thrombi may occur inside the pump when ACT is controlled under 250 sec. During the weaning stage or low flow (under 2 L/min), over 250 sec of ACT is recommended to assure the safety of the patient.

Coronary Microcirculation During Left Heart Bypass with a Centrifugal Pump

To estimate coronary microcirculation during left heart bypass (LHB), we performed an experimental comparison study of LHB and intraaortic balloon pumping (1ABP). LHB was performed with a BioMedicus BP-80 pump supporting half of the flow of cardiac output whereas the IABP was pumped in a 1:1 mode for cardiogenic shock in a swine model. Coronary circulations were analyzed by electromagnetic flowmeter, pulsed Doppler velocimeter, and laser Doppler flowmeter. Left ventricular end-diastolic pressure (LVEDP) was reduced significantly by LHB. Although there was no significant difference in epicardial flow between the LHB and IABP groups, endocardial flow was increased significantly by LHB. In the LHB group, the systolic reverse wave of the coronary velocity called a myocardial invalid circulation was reduced remarkably. There was a significant inverse correlation between endocardial flow and LVEDP. These results suggested that LHB was more effective for myocardial microcirculation than was IABP.

Development of an implantable small right ventricular assist device.

Currently, at least two permanent implantable left ventricular assist devices (LVADs) are used clinically. Unfortunately, there is no small implantable right ventricular assist device (RVAD) available, even though at least 25-30% of this patient population has right ventricular failure. If a small implantable RVAD were available, biventricular assist could support patients with right ventricular failure. A small atraumatic and antithrombogenic RVAD is being developed to meet this clinical need. This small centrifugal blood pump, the Gyro PI pump, is 6.5 cm in diameter and 4.6 cm in height and has three unique characteristics to prevent thrombus formation: (1) the double pivot bearing and magnetic coupling system enable this pump to be completely sealless; (2) the secondary vanes at the bottom of the impeller accelerate the blood flow and prevent blood stagnation; and (3) the eccentric inlet port enables the top female bearing to be embedded into the top housing and decrease blood cell trauma. The inflow conduit consists of a wire reinforced tube and a hat-shaped tip that is biolized with gelatin to create a thrombus resistant material. This conduit is directly implanted into the right ventricle, and the outflow conduit is anastomosed to the PA. The pump can be implanted inside the abdominal wall or in the thoracic cavity. Biocompatibility of this pump was proved in two calves by thrombus free implantation as an LVAD for 284 days and 200 days. Two RVAD implantations were conducted, aiming for 1-month system feasibility studies. During the month, the RVADs operated satisfactorily without any thromboembolic incident. No blood clots or abnormal findings were seen inside the pump, nor were there abnormal findings in the explanted lungs except for small areas of atelectasis. The pump flow was 3.02 +/- 0.38 L/min in calf 1 and 3.75 +/- 1.18 L/min in calf 2. The power requirement was 7.28 +/- 0.43W for calf 1 and 14.52 +/- 3.93W for calf 2. The PaO2 was 72.0 +/- 3.60 mm Hg (calf 1) and 72.0 +/- 7.63 mm Hg (calf 2); PaCO2 was 38.3 +/- 2.17 mm Hg (calf 1) and 34.1 +/- 1.95 mm Hg (calf 2); and SaO2 was 94.1 +/- 1.37% (calf1) and 95.0 +/- 1.95% (calf 2). Gas exchange via the lungs was maintained. These studies indicate that the Gyro PI pump is suitable as a single implantable RVAD, and is a feasible RVAD as a part of a BiVAD system in terms of pump performance and thrombus resistance.