Compact prosthetic total heart.
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Animals↗
Biomedical subjects
T Akutsu
Publications and source records attributed to T Akutsu.
Problems in calf lungs immediately after implantation of an artificial heart.
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Animals↗
Natural heart recovery under left ventricular assist device pumping studied by echocardiography.
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Adult↗
Development of a novel biocompatibility test method based on intracellular calcium ion mobilization.
This paper presents a novel evaluation method for determining platelet/material interaction at the transmembrane level by incorporation of a Ca-sensitive fluorophore (Fura-2) into platelets. The transmembrane stimulation of platelets which are eluted from commercially available artificial dialyzers was quantitatively measured as the elevation of intracellular free calcium ion concentration. This method clearly differentiated platelet response to hydrophilic (ethylene vinyl alcohol copolymer and cellulose) vs. hydrophobic (polyacrylonitrile and cellulose acetate) membranes, and offers a versatile means to understanding platelet/material interaction.
Biocompatible Materials↗
Molecular understanding of cellular adhesion on artificial surfaces.
This study was conducted to clarify cellular adhesion mechanisms of blood cells (platelets [PLT] and white blood cells [WBC]) and vascular endothelial cells at the molecular level. This study indicated that the adhesion of three cellular systems to proteins such as fibronectin and fibrinogen proceeds via the RGD (Arg-Gly-Asp) ligand-receptor interaction, in which the RGD tripeptidyl sequence is the minimal amino acid sequence common to adhesive proteins. This was evident from the dose-dependent inhibitory effect of RGD-containing peptide on cellular adhesion. Additional supporting evidence was the presence of PLT and WBC receptors, which molecularly recognize RGD, verified by fluorescein-labelled RGD-containing peptide. The adhesion of vascular endothelial cells was also predominantly controlled by the ligand-receptor mechanism, and participation of complement activation on WBC adhesion was demonstrated as well. The adhesion of WBCs on surface hydroxyl group-bearing polymers proceeded via the CR3 receptor-C3b ligand interaction, in which activated complement factor C3b is chemically fixed upon complement activation. Thus, the molecular understanding of cellular adhesion mechanisms provide the basis of biocompatibility for implantation and extracorporeal circulation, as well as molecular design of artificial and bioartificial organs.
Animals↗
Influences of ventricular assist device pumping on blood coagulation.
A left ventricular assist device (VAD) with a smooth surface of segmented polyurethane was implanted in five goats for 10-55 days, and plasma levels of fibrinogen (Fg), prekallikrein (PK), fibrinogen, fibrin degradation products (FDP), antithrombin III (AT III), prothrombin time (PT), partial thromboplastin time (PTT), platelet (Pl) count, and platelet aggregation (PlAg) induced by adenosine diphosphate were measured during the experiment. Heparin was administered during surgery and no systemic antithrombotic therapy was given thereafter. Before the third postoperative day (POD), plasma levels of Fg and PK were at their lowest, and increased afterward. Between the second and fifth POD PT and PTT increased to 130-160%, and returned to normal gradually. Plasma FDP appeared on the second POD and reached peak values of 10-40 micrograms/ml on the sixth POD. Platelet and AT III levels showed no uniform tendency, but the rate of PlAg decreased to levels of 6-77% before the fifth POD and remained low at approximately 80%, influenced by the pumping even after the 25th POD. In summary, VADs themselves activated coagulation and induced consumption coagulopathy to some degree. However, most of the parameters returned to normal within 2 weeks.
Animals↗
Regulation of coronary circulation during left ventricular assist.
Regulatory mechanisms of coronary circulation during left ventricular assist (LVA) were studied in chronic experiments using adult goats. In normal heart studies (n = 3), circumflex coronary artery flow (CxF) and endocardial blood flow (MBF) decreased in proportion to decrease of tension time index (TTI). Mean CxF/TTI was constant at 0.22, whether the LVA functioned or not. In the left anterior descending branch ligation model (AMI) study (n = 2), CxF decreased according to decrease of TTI throughout the experiment, if the bypass ratio was kept within a normal range of systemic pressure. Mean CxF/TTI was maintained at approximately 0.21 by LVA, fell to 0.16 when LVA was turned off during the early stages. Coronary circulation during LVA was regulated by oxygen demand if systemic circulation was maintained, and LVA improved oxygen demand-supply balance in failing hearts.
Animals↗
An electrohydraulic ventricular assist system with a linear actuator.
An electrohydraulic ventricular assist system with a linear actuator was developed, and in vitro and in vivo evaluations were performed. During in vitro evaluations this system could yield 5.6 L/min of pump flow against a mean afterload of 100 mmHg. Durability tests were performed for more than 4 months. The system was implanted in three goats and a maximum pump flow of 4.2 L/min was obtained against a mean afterload of 100 mmHg, and 3.2 L/min against 130 mmHg. These evaluations have proven that the system can maintain stable hemodynamics under various conditions.
Animals↗
Experimental evaluation and clinical application of a pediatric ventricular assist device.
A pneumatic pediatric ventricular assist device (VAD) with a stroke volume of 20 ml has been developed to treat post-operative heart failure (HF), and maintain transplant candidates. The polyurethane VAD has two #21 Bjork-Shiley valves and the internal diameter of the cannula is either 6 or 8 mm. Hemodynamic effects of a left ventricular assist device (LVAD) on a HF after Fontan's procedure model, and those of a right ventricular assist device (RVAD) on right HF with pulmonary hypertension model, were investigated in acute experiments with four and five dogs, respectively. In the former, the pressure gradient across the lung and cardiac output (CO) increased with an LVAD; right atrial pressure decreased and CO increased with an RVAD in the latter. The pump was implanted as an LVAD in 8 young goats, 9-22 kg in weight, for 4-10 weeks and favorable in vivo performance was demonstrated. The VAD system was applied as an LVAD to two postcardiotomy patients, a 12 kg boy with a ventricular septal defect, and a 13 kg boy with an endocardial cushion defect. In these cases, CO was well maintained at the level of 2.5-4.1 L/min/m2 for three and seven days, respectively, and the pump was removed. In conclusion, this VAD will become a promising circulatory support system for pediatric uses.
Animals↗
Left ventricular assist system with a simplified cannulation technique.
A simplified cannulation system was developed without thoracotomy for a ventricular assist system (VAS) that will be applicable even in an emergency. This system consists of an air driven and diaphragm type pump, cannulae, and devices for insertion. The inlet cannula was inserted into the left atrium through the femoral vein using a modified brockenbrough transseptal method. This system was installed without thoracotomy in a chronic experiment in two goats and was removed without any trouble after 14 days of pumping. In a 40 day experiment with this system implanted between the left atrium and the aorta, bypass flow was maintained at 2.7 to 3.3 L/min, and plasma free hemoglobin levels were below 7 mg/dl. When this system was implanted between the left atrium and the aorta, and activated in an induced heart failure goat, output through the pump was 3.0 +/- 0.4 L/min, and mean aortic pressure was increased to 91.7 +/- 15.9 mmHg from 55.8 +/- 15.4 mmHg. This system takes a middle position between an IABP and VAS with thoracotomy in capability of circulatory support and convenience.
Animals↗
A novel method for long-term respiratory support.
The authors designed a new extracorporeal membrane oxygenation (ECMO) method using a right ventricular assist device (RVAD) system and a membrane oxygenator (MO). An air-driven diaphragm type RVAD was implanted between the right atrium and the pulmonary artery in five goats, and an MO was set on the outlet conduit of the RVAD 2 weeks postoperatively. The MOs used in this study are silicon sheet MOs and prototype MOs using a novel multilayered composite membrane. Respiratory support with this system, under systemic heparinization, could be conducted for 4-8 days without major problems. This method solved several difficulties with ECMO, such as surgical bleeding, serum leakage, destruction of the blood components from the pump system, inadequate bypass flow, and fatal systemic thrombosis. This method is suitable for long-term respiratory support, especially as a bridge before lung or heart-lung transplantation.
Animals↗
Development of a novel artificial matrix with cell adhesion peptides for cell culture and artificial and hybrid organs.
The authors present a novel artificial matrix with high cell adhesion and growth rate that was produced by chemical fixation of an RGD-containing peptide (Arg-Gly-Asp) on a polyvinyl alcohol (PVA) surface. The logical sequence behind the molecular design of an artificial matrix that mimics natural adhesive proteins, such as fibronectin, is based on the fact that an RGD tripeptidyl amino sequence is the minimal common adhesion site of adhesive proteins. Activation of surface hydroxyl groups by carbonyl diimidazole successfully incorporated GRGDSP (Gly-Arg-Gly-Asp-Ser-Pro) onto PVA films. The resultant film surface was found to be bioactive, molecularly recognizing the adhesive receptor of bovine endothelial cells. Thus, the artificial matrix mimics active adhesion sites and serves as a novel artificial matrix that may be useful for cell culture, tissue-compatible implants, and hybrid artificial organs.
Animals↗
Can heparin immobilized surfaces maintain nonthrombogenic activity during in vivo long-term implantation?
The authors previously demonstrated that heparin immobilized surfaces showed excellent nonthrombogenic properties for extracorporeal membrane oxygenation experiments as long as 168 hr. The characteristics of the heparin immobilized surfaces include high heparin bioactivity and prevention of platelet adhesion and complement activation. However, it is not known whether the heparin immobilized surfaces would be effective for in vivo long-term implantation. Heparin bioactivity may be lost because of complete degradation or blocking of binding sites on heparin by adsorbed proteins. This study attempted to elucidate the in vivo long-term fate of heparin immobilized surfaces. The blood contacting surfaces of the ventricular assist device (VAD) made from polyurethane was modified with heparin immobilization and evaluated in a long-term sheep left VAD (LVAD) model for as long as 3 months. After removal of the VAD, heparin bioactivity was measured by Factor Xa assay. The blood contacting surfaces were analyzed with a scanning electron microscope, and the adsorbed proteins on the surfaces of the diaphragm were analyzed by SDS-PAGE and Western blotting. The thickness of adsorbed proteins on the surfaces also was measured by a confocal laser microscope. For the control ventricular assist devices, thrombus formation was observed within 1 month, whereas heparin immobilized VADs were able to operate thrombus free for periods as long as 3 months. The control surfaces demonstrated a thick adsorbed protein layer on thin surfaces, whereas heparin immobilized surfaces maintained thinner adsorbed proteins on thin surfaces. Anti Factor Xa activity of the heparinized surfaces disappeared after 15 days, but the surfaces remained nonthrombogenic even after heparin bioactivity was completely lost. The protein composition analyzed by SDS-PAGE showed an albumin dominant pattern on the heparinized surfaces. The band of 110 kD corresponding to C3b was detected only on the control surfaces, which possibly activated complement, and subsequently activated platelets and coagulation. Immunoblot showed degradation products of fibronectin and vitronectin on the control surfaces, which probably were promoted by surface generated protease, whereas the heparinized surfaces showed minimal degradation throughout the experimental periods. These results suggest that the heparin moiety has an ability to control adsorbed proteins, thereby inhibiting thrombus formation during in vivo long-term implantation.
Adsorption↗
Recent progress in the development of Terumo implantable left ventricular assist system.
The research group of the Terumo Corporation, the NTN Corporation, and Setsunan University (T. Akamatsu) has been developing an implantable left ventricular assist system (ILVAS) featuring a centrifugal blood pump with a magnetically suspended impeller (MSCP). The impeller of the MSCP is suspended by a magnetic bearing, providing contact-free rotation of the impeller inside the pump housing. Thus the MSCP is expected to provide years of long-term durability. Ex vivo chronic sheep experiments using the extracorporeal model (Model I) demonstrated long-term durability, nonthrombogenicity, and a low hemolysis rate (plasma free Hb <6 mg/dl) for more than 2 years. The prototype implantable model (Model II; 196 ml, 400 g) was evaluated ex vivo in 2 sheep and intrathoracically implanted in a small sheep (45 kg). These experiments were terminated at 70, 79, and 17 days, respectively, because of blood leakage through the connector system within the housing of Model II. There was no thrombus formation on the retrieved pump surfaces. A new connector system was introduced to the Model II pump (modified Model II), and the pump was intrathoracically implanted in a sheep. Pump flow rate was maintained at 3-7 L/min at 1700-1800 rpm. The temperature elevation on the surfaces of the motor and the electromagnet inside the pump casing was kept less than 6 degrees C. The temperature of the tissue adjacent to the pump casing became normal 10 days postoperatively. The sheep survived for more than 5 months without any sign of mechanical failure or thromboembolic complication. In vitro real-time endurance tests of motor bearings made of stainless steel and silicone nitride have been conducted for more than 1 year without any sign of bearing wear. The next prototype system (Model III), with an implantable controller and a new MSCP with reduced input power, has been developed with a view toward a totally implantable LVAS.
Alanine Transaminase↗
Terumo implantable left ventricular assist system: results of long-term animal study.
The research group of Terumo Corporation, NTN Corporation, and the Setsunan University have been developing an implantable left ventricular assist system (T-ILVAS) featuring a centrifugal blood pump with a magnetically suspended impeller (MSCP). The present study describes results of chronic animal experiments using the MSCP. The MSCP has been tested ex vivo and in vivo in 6 sheep as a left heart bypass between the left ventricular apex and descending aorta. Ex vivo chronic sheep experiments using Model I demonstrated long-term durability, nonthrombogenicity, low hemolysis (<6 mg/dl), and excellent stability of the magnetic bearing with long-term survival for up to 864 days. Average pump flow rate was 4 L/min at a fixed rotational speed of 2000 rpm. Power spectral analyses of heart rate, aortic pressure, and blood temperature maintained normal 1/f fluctuation during the study. The retrieved pump was completely free from thrombus formation and there was no evidence of infarct in major organs. The implantable Model II was evaluated ex vivo in two sheep and intra-thoracically implanted in a sheep. These experiments were terminated at 70, 79, and 17 days due to blood leakage through the connector system within the housing. No thrombus formation was observed in any of the retrieved pumps. A modified Model II with a new connector system was subsequently intra-thoracically implanted in a sheep. The sheep survived for 482 days without any sign of thromboembolic complication or hemolysis at a fixed rotational speed of 1700 rpm and an average pump flow rate of 5 L/min. There was no intra-device thrombus formation or infarct in major organs. The Model III system, consisting of an implantable controller and a new MSCP with a reduced input power of 13 W, has been developed and implanted in a chronic sheep model. The MSCP was implanted in the left pleural space and the controller in the abdominal wall. The experiment is still in progress for more than 30 days without any significant complication to date. These animal studies strongly suggest the feasibility of the MSCP for use as long-term circulatory assist.
Animals↗
Delayed adverse reactions to iodinated contrast media and their risk factors.
PURPOSE: The present prospective survey was performed to obtain information on delayed adverse reactions (DARs) to five types of low-osmolar iodinated contrast media, including their frequency, common manifestations, and the patient's history of allergy. METHODS: We investigated data from 15,890 consecutive patients who underwent contrast-enhanced computed tomography (CT) during a 15-month period. All patients were given a questionnaire asking about the occurrence of DARs, their symptoms and duration, and asked to consult a dermatologist if they had a skin reaction. RESULTS: Of 11,121 patients who returned the questionnaire (response rate, 70.0%), DARs were observed in 1,058 patients (9.5%). DARs tended to occur with higher incidence in patients with no previous history of examinations using contrast media, with past adverse reactions caused by contrast media, with a history of allergy, or with a serum creatinine level greater than 2.0 mg/dl. Among the 331 patients who reported skin reactions, 41 patients consulted a dermatologist. Skin reactions were observed significantly more frequently in patients for whom iotrolan was used, and 60% of these reactions were severe or moderate. CONCLUSIONS: Four risk factors for DARs were identified in the present investigation.
Adolescent↗
Donor-heart evaluation by monitoring the left ventricular pressure-volume relationship: clinical observations.
Fourteen donor hearts were assessed by measurement of dopamine requirement, basic hemodynamic parameters (for example, systolic blood pressure), and the left ventricular pressure-volume relationship. The latter function was measured by a combination microtipped manometer/conductance catheter placed in the left ventricle through the ascending aorta. With an isoproterenol dose 24 hours after transplantation as the measure of cardiac performance, multiple linear regression analysis indicated that the ratio of arterial elastance (Ea) to left ventricular end-systolic elastance (Ees), ventriculoarterial coupling (Ea/Ees), and myocardial ischemic time were good predictors of posttransplantation cardiac performance. Dopamine requirement and basic hemodynamic data were not. Twelve implanted hearts showed an Ea/Ees of less than 1.0 and showed good early (less than 24 hours) and late function. Two hearts considered on clinical grounds to be unsuitable for transplantation showed an Ea/Ees of more than 1.0. The data suggest that measurement of the left ventricular pressure-volume relationship would appear to be a clinically useful predictor of donor-heart performance after transplantation.
Adult↗
Management of postoperative biventricular failure by means of a right ventricular assist device and an intraaortic balloon pump.
Right dominant biventricular failure often accompanies the end-stage of combined rheumatic valvular disease and some kinds of congenital heart disease. The management of right ventricular failure with conventional medical treatment, however, has encountered many difficulties. Mechanical support of the right ventricle with an RVAD (right ventricular assist device) has proved useful and effective. Seven patients who could not be weaned from cardiopulmonary bypass were subsequently transferred to an intraaortic balloon pump (IABP) and RVAD. Among these, five had severe combined rheumatic valvular disease, one had congenital heart disease and was advanced in age, and the other had a left atrial myxoma with tricuspid regurgitation. Preoperatively, all of these patients had had biventricular failure. All seven cases were successfully weaned from RVAD, and later from IABP. Five patients were discharged from the hospital and returned to normal daily life. Two patients died during their postoperative course. Long-term survival rate was 71%. Mechanical assist with RVAD and IABP seemed to be effective in the management of right dominant biventricular failure, such as that seen in combined valvular disease and some kinds of congenital heart disease.
Cardiac Surgical Procedures↗