Takeshi Nakatani

Preparation and Recellularization of Tissue Engineered Bioscaffold for Heart Valve Replacement

Tissue engineered grafts based on polymeric or acellular xenogeneric matrices have been widely studied, and found to have greater durability and functionality with growth potential and less immunogenicity than current bioprostheses. On the other hand, there are still several problems to be solved such as degradation control of biodegradable polymeric scaffolds and unwanted transfer of unknown animal related infectious diseases. In this chapter, our novel tissue processing of decellularization named PowerGraft by ultrahigh pressure treatment for safe tissue transplantation is reported. Porcine heart valves were isolated under sterile conditions and treated by cold isostatic pressing (CIP) at 4°C for disruption of donor cells. The cell debris was then washed out in PBS under microwave irradiation at 4°C. The tissues were completely cell free when they were treated by a CIP of 980 MPa (10,000 atm) for 10 min. There was no porcine endogeneous retrovirus (PERV) detected in the treated tissue. There were no significant changes in biomechanical properties of breaking strength and elastic modulus. From the in vitro incubation test, the tissues were disinfected when CIP was applied to the tissues contaminated by normal bacteria floras. The endothelial cells were well seeded on the acellular bioscaffold by the roller and circulation culture systems sequentially. This PowerGraft processing may provide a more durable and safe bioscaffold for tissue transplantation.

New Compact Integrated Cardiopulmonary Bypass Unit (CICU) for Percutaneous Cardiopulmonary Support

The cardiopulmonary bypass technique has been used for circulatory support [1] and cardiac resuscitation [2]. Recently, percutaneous cardiopulmonary support (PCPS) with large-bore thin-walled cannulas has become valued because of its easy application in emergency cases [3,4], and because of its use for supported percutaneous transluminal coronary angioplasty (PTCA) [5,6]; it has rapidly achieved widespread popularity. Despite the increased clinical demands, a cardiopulmonary bypass unit specially designed for PCPS has not yet been developed. We have developed a new compact integrated cardiopulmonary bypass unit (CICU) for PCPS, and applied it clinically. Herein, we describe this unit and the results achieved with its initial clinical use.

An electrohydraulic totally implantable artificial heart with a motor-integrated regenerative pump and its computer control

An electrohydraulic totally implantable artificial heart which has a motor-integrated regenerative pump was developed. The system consists of left and right diaphragm-type blood pumps which are implanted in the thorax with a separately placed electrohydraulic actuator in the abdominal region. The blood pump was designed to have an appropriate anatomical fitting in a human thorax. The actuator is a regenerative pump which is able to pump fluid against a high head. The height, diameter, and weight of the actuator are 32.5 mm, 73 mm, and 350 g, respectively. The rotor-magnet of the brushless DC motor is embedded in the impeller of the regenerative pump in order to miniaturize the actuator and increase durability by reducing the number of moving parts. A 32-b microcomputer controls the motor of the actuator. The detection algorithm of the pumping condition was developed by using the TMSTR (time-sequential multiple-state transition representation) linguistic technique to control the artificial heart correctly and safely. The feasibility of the devices was confirmed by in vivo and in vitro experiments.<<ETX>>

Usefulness of Nuclear Medicine: “PET/SPECT Imaging” for Management of Recipients after Heart Transplantation

Heart transplantation(HTx)in Japan started in 1992 after putting the Organ Transplant Law into force. Even after the amendment of this law in 2010, numbers of HTx performed in Japan has been much less than other countries, however, the outcome of HTx in Japan is much superior to that of international registry. For the management after HTx, surveillance of acute cellular rejection, cardiac allograft vasculopathy(CAV), infections, renal dysfunction, malignancies is essential. Nuclear medicine, such as myocardial perfusion imaging, Ga scintigraphy, F-FDG PET, etc., has been utilized for detection of these rejections and complications, adding to other modalities. Moreover, re-innervation from denervated heart is unique phenomenon which is observed in HTx recipients. For the evaluation of re-innervation in transplanted heart, I-metaiodobenzylguanidine (MIBG), which is the analogue of norepinephrine, has been utilized. Then, several reports described that the degree of re-innervation was related to sympathetic functional recovery, such as responses of the heart rate and contractile function to exercise. As described above, nuclear medicine has contributed to recipient9s care and management after HTx. However, invasive techniques, such as endomyocardial biopsy, coronary angiography, etc., have played a major role in management of recipients, because of high reliability for detection of rejections and complications, compared with other non-invasive modalities. So, we professional of imaging diagnosis have to keep on challenging to offer securer and easier care to HTx recipients.

Prolonged circulatory maintenance with a left ventricular assist device during cardiac arrest

The occurrence of an intractable severe biventricular failure, ventricular fibrillation, or cardiac arrest during the use of a left ventricular assist device (LVAD) is a serious problem. The purpose of this study is to examine the feasibility of prolonged circulatory maintenance with an LVAD alone during cardiac arrest until heart transplantation is performed. After an LVAD was inplanted between the left atrium and aorta in 12 goats, ventricular fibrillation was induced. When pulmonary vascular resistance was in the normal range (less than 15 000 dynes.s.cm−5.kg), the circulation was well maintained with an LVAD alone as long as right atrial pressure was kept at 14–16 mmHg. Under such conditions, the flow fluctuated between 80 and 140 ml/kg/min depending on the animal’s demand, and the mean arterial pressure was kept above 80 mmHg. The goats behaved quite normally. However, pooling of pleural effusion was a serious problem in maintaining normal circulation for a prolonged duration. Maintenance of the total protein level above 6.0 g/dl could delay or prevent pooling of effusion. The longest survival period to date has been 38 days. When pulmonary vascular resistance is in the normal range, an LVAD alone during cardiac arrest will provide sufficient time to try a further treatment such as heart transplantation or total artificial heart replacement.

Influence of Long-Term Support upon the Severely Failing Left Ventricle

It is unclear how long-term support with a left ventricular assist system (LVAS) affects the severely failing left ventricle (LV). From 1994, we applied our LVAS to seven patients with profound heart failure. Of those, six patients were supported for more than 3 weeks. The etiologies of heart failure were valvular heart disease (VHD) in one, ischemic heart disease (IHD) in two, dilated phase hypertrophic cardiomyopathy (DHCM) in one, and dilated cardiomyopathy (DCM) in two. In one patient, biventricular assist was performed because of coexisting severe right heart failure. Each LVAS was installed between the left atrium and the ascending aorta and the pump was positioned paracorporeally. After stabilization of general condition, exercise was started. The natural heart size was examined and systolic heart function was evaluated by the systolic time interval (STI) under LVAS pumping by using echocardiography. This STI was calculated from the equation: ejection time divided by pre-ejection period measured from aortic valve movement. At the beginning of assistance, the STI was low ( 1 and their LVDd decreased to <70mm. Two of them (1CM, 1VHD) are doing well now 2 years after LVAS removal. From these data, the cardiac function of the patient with a severely failing LV may improve when LV dilatation decreases and STI increases through long-term LVAS support.

Clinical considerations of life-saving effect of left ventricular assist device

Our left ventricular assist device (LVAD), containing an automatic level control of total systemic flow and left atrial pressure, was clinically applied in 16 patients (aged 3–73 years) with cardiogenic shock following acute myocardial infarction (AMI; nine cases) and cardiac surgery (seven cases). The entire circulation was well maintained at the normal level and the LVAD was successfully removed in nine patients (56%). Three patients (19%) could be discharged with a satisfactory condition. Removal of left ventricular overload with the use of the LVAD prevented overextension of the impaired myocardium, and the gradual increase in left ventricular work promoted the compensatory ability of the residual myocardium. This recovery mechanism was established in chronic animal experiments using goats. However, the clinical problem with the treatment was the preexisting myocardial damage, such as fibrosis caused by rheumatic myocarditis and ischemia in the residual myocardium. In addition, although the natural heart recover, several patients died of multiple organ failure, which had developed during the prolonged low perfusion period prior to left ventricular assistance. In conclusion, the timely use of LVAD proved to be effective in treatment of cardiogenic shock, but preexisting myocardial damage and delayed application will considerably decrease the chance of a favorable recovery in clinical cases.

Preliminary Trial of Lower Leg Thermal Therapy for Patients with Terminal Heart Failure Fitted with Left Ventricular Assist Device

In 1989 Tei et al. developed Waon therapy for heart failure that uses a dry sauna (Tei et al., 1994; Tei et al., 1995; Tei 2007). Waon therapy means a thermal therapy using special‐ ly designed sauna bath for heart failure. In the therapy, patients were placed in a sittingposition in a 60 ◦C far infrared-ray dry sauna system for 15 min, and then after leaving the sauna, they underwent bed rest with a blanket to keep them warm for an additional 30 min. And fluids corresponding to perspiration are supplied to protect against dehydra‐ tion at the end of therapy. In this specially designed sauna system, the body core temper‐ ature has increased by 1.0–1.2°C, various beneficial effects for symptoms of heart failure were found (Tei, 2007).

A Novel Micro-Angiography Detecting Angiogenesis, Application for Autologous Bone Marrow Mononuclear Cells Transplantation in the Patients with Critical Limb Ischemia

Conventional Anigiographic Findings in Autologous Bone Marrow Mononuclear Cells Transplantation for Critical Limb Ischemia: Bone marrow mononuclear cells have many of the characteristics of stem cells for mesenchymal tissues, and secrete many angiogenic cytokines. We performed autologous transplantation of bone marrow mononuclear cells in six patients with critical limb ischemia due to Buerger disease, who were not candidates for catheter or surgical revascularization. Leg pains at rest and skin ulcers improved after bone marrow transplantation in all patients, although significant collateral developments after the therapy by conventional angiography could not be observed. Autologous transplantation of bone marrow mononuclear cells including stem cells improved critical limb ischemia due to Buerger disease. Neovascularization after therapeutic angiogenesis might be quite small and could not be visualized by conventional angiography.

Evaluation of a Newly Developed, Heparin-Bonded Artificial Lung in Chronic Animal Experiments

Our artificial lung (AL) for long-term extracorporeal membrane oxygenation (ECMO) consists of a special membrane in which micropores on the outer surface of the hollow fibers are blind-ended to eliminate direct blood-gas contact, and the entire blood-contacting surface is treated with covalent heparin binding to promote antithrombogenicity. Chronic performance of the AL was evaluated for gas-exchange function and thromboresistant properties in four goats weighing 28–36 kg, using a venoarterial bypass circuit perfused by means of a pneumatic ventricular assist device for up to 14 days. Serum leakage was completely prevented in all the devices throughout the experimental period. With 3.3–4.21/min of blood flow and 10–151/min of oxygen flow, the AL transferred 166 ± 25ml/min of oxygen and 116 ± 41ml/min of carbon dioxide. Platelet counts and antithrombin III levels significantly decreased during the initial 3 days but rebounded thereafter. Only in one AL was macroscopic thrombus formation observed, presumably related to severe infection. Scanning electron microscopy showed the surface of hollow fibers to be free of thrombus, while fibrin deposits were observed in all devices, mainly on the polyester threads used for weaving the hollow fibers. These results indicate that our new AL can be used for prolonged ECMO, although further improvement in thromboresistant properties should be achieved.