[Thoracic Aortic Injury after Spinal Fusion;Report of a Case].

A 32-year-old female visited our hospital with back pain. She had undergone spinal fusion for scoliosis at another hospital. She visited our hospital because she was informed that the metal rod had broken. Computed tomography(CT) revealed a suspected penetration of one of the screws into the descending aorta, and aortography showed the aortic wall dented by the screw. The aorta was exposed via thoracotomy, and the top of the screw was found penetrating into the adventitia of the aorta. After carefully detaching the region from the screw, the defect of the adventitia was repaired by continuous suture. The screw was cut to avoid further injury. Several days later, re-operation was successfully performed for the scoliosis.

[Sternal Nonunion after Open Heart Surgery through a Partial Sternotomy;Report of a Case].

Sternal nonunion is an uncommon complication after a sternal wound and some cases have been reported as a complication of open heart surgery. A 28-year-old male suffered from persistent sternal pain. Six years ago, open heart surgery was performed through a partial sternotomy with transverse sternotomy. The sternal nonunion was repaired using 3 sternal wires and 1 absorbable sternal pin. Three years later, the patient experienced recurrence of persistent sternal pain with clicking, because all of the sternal wires had ruptured and the sternal healing was incomplete. The patient was treated with adequate debridement and a technique using metal plates and autogenous bone grafts, which provided excellent pain relief. A transverse sternotomy potentially exposes the patient to the risk of sternal nonunion, which should be treated using autogenous bone grafting.

[Primary Malignant Pericardial Mesothelioma;Report of a Case].

A 69-year-old male was referred to our hospital after being diagnosed as having pericarditis with pericardial effusion. The symptoms of tamponade disappeared after the effusion was drained;although the cause of pericarditis remained unidentified. About 4 months later, the tamponade symptoms recurred due to the thickened nodular pericardium. Partial pericardiectomy was performed, however the patient died on the 52nd day after surgery. Immunohistological examination with calretinin led to the diagnosis of primary malignant pericardial mesothelioma, which was an extremely rare pathology. Because the hyaluronic acid content of the effusion has been reported as a diagnostic aid for malignant mesothelioma, routine examination of the hyaluronic acid content for pericarditis with pericardial effusion may be necessary for early diagnosis and to improve prognosis.

[Off-pump surgery for coronary-pulmonary artery fistula with giant coronary aneurysm; report of a case].

A 60-year-old male was referred to our hospital due to suspected chronic heart failure. He also had a symptom of ischemic heart disease. The multi-detector row computed tomography (MDCT) demonstrated the coronary-pulmonary artery fistula with a giant coronary aneurysm, which was partly thrombosed. Two abnormal arteries to the aneurysm and the outflow to the pulmonary artery were clearly detected. Intraoperative epicardial echocardiography revealed the complete interruption of blood flow and the thrombus formation in the coronary aneurysm, that was achieved just by ligation of 2 arteries under off-pump surgery. Generally, congenital coronary-pulmonary artery fistula has complex morphological variations. In this case, MDCT and epicardial echocardiography were useful for the surgical decision-making to avoid the residual and/or the recurrent fistula.

[Coronary artery bypass grafting after total esophagectomy].

A 69-year-old male with a history of total esophagectomy and substernal placement of the gastric tube for esophageal carcinoma was admitted due to an unstable angina. Cardiac catheterization revealed a severe stenosis just proximal to the left anterior descending coronary artery and a 75% stenosis of the right coronary artery. Intraaortic balloon pumping was started in the catheter laboratory. Off-pump coronary artery bypass grafting was performed through left thoracotomy. The left internal mammary artery could not be utilized as a bypass graft to the left anterior descending artery due to severe substernal adhesion. Percutaneous coronary intervention was selected for the revascularization of the right coronary artery lesion.

Feasibility of a new hollow fiber silicone membrane oxygenator for long-term ECMO application.

Currently in United States, there are no clinically-applicable hollow fiber extracorporeal membrane oxygenation (ECMO) oxygenators available. Therefore, our laboratory is in the process of developing a silicone hollow fiber membrane oxygenator for long-term ECMO usage. This oxygenator incorporates an ultrathin silicone hollow fiber. At this time, a specially-modified blood flow distributor (one chamber distributor) is centered in the module to prevent blood stagnation. An ex vivo long-term durability test for ECMO was performed using a healthy miniature calf for 2 weeks. Venous blood was drained from the left jugular vein of a calf, passed through the oxygenator and infused into the left carotid artery using a Gyro C1E3 centrifugal blood pump. A successful 2-week ex vivo experiment was performed. The O2 and CO2 gas transfer rates were maintained at the same value of 40 m/min at a blood flow rate of 1 L/min flow and V/Q=3 (V=gas flow rate; Q=blood flow rate). The plasma free hemoglobin was maintained around 5 mg/dl. After the experiment, no blood clot formation was observed in the module and no abnormal necropsy findings were found. These data suggest that the performance of this newly-improved oxygenator was stable, reliable, and acceptable for long-term ECMO.

Long-term ex vivo bovine experiments with the Gyro C1E3 centrifugal blood pump.

Centrifugal blood pumps are used widely for cardiopulmonary bypass, as ventricular assist devices, and for extracorporeal membrane oxygenation (ECMO). However, there is no centrifugal blood pump that is suitable for long-term ECMO. The authors developed the Gyro C1E3 centrifugal blood pump (Kyocera Corporation, Kyoto, Japan), which has superior antithrombogenic, antitraumatic, and hydraulic features in comparison with the conventional centrifugal blood pumps. Five ex vivo long-term durability tests of the Gyro C1E3 were performed using healthy miniature calves. The ECMO circuit was composed of a prototype hollow fiber silicone membrane oxygenator and a Gyro C1E3 pump. Venous blood was drained from the left jugular vein of a calf, passed through the oxygenator and infused into the left carotid artery using a Gyro C1E3. Ex vivo studies were performed from 7 to 15 days at a blood flow rate of 1 L/min. During this period, the Gyro C1E3 demonstrated a stable performance without exchanging the pump. Bleeding complications were the major reason for termination of each experiment. Rotational speed was maintained around 2,000 rpm. All five calves demonstrated neither abnormal signs nor abnormal blood examination data throughout the experiment. Neither clot nor thrombus formations were found during the necropsy in the cannula or pump nor were infarctions observed in any of the major organs. In conclusion, the Gyro C1E3 showed a stable and reliable performance during long-term ex vivo bovine experiments under the conditions tested.

Development of a flexible inflow cannula with titanium inflow tip for the NEDO biventricular assist device.

A newly designed flexible inflow cannula has been developed for a biventricular assist device (BVAD). The inflow tip was designed for long-term ventricle drainage. Considering the anatomic differences between the right and left ventricles, a flexible inflow cannula, as a mass production model with a titanium tip, was developed and investigated in chronic BVAD animal experiments using the NEDO permanently implantable centrifugal blood pump. These flexible inflow cannulae consist of flexible plastic tubing with wire supported, titanium left and right tips. The right titanium inflow tip was designed with inner and outer stoppers to be inserted into the right ventricle wall and a beak shape to avoid sucking. The left tip was designed to be inserted into the left ventricle cavity. Five chronic BVAD bovine studies were performed to investigate the new beak shaped titanium tip. In these studies, the new beak shaped titanium tip and cannula prevented stenosis by a proliferation of pseudoneointimal, and supplied adequate blood flow to the pump without sucking. This newly designed inflow cannula with the beak shaped titanium tip was successfully implanted for 90 days.

Physiological adaptation to a nonpulsatile biventricular assist system.

Physiological adaptation of the recipient to a nonpulsatile biventricular assist system (NPBVAS) is not well understood. The aim of this study is to evaluate the physiological adaptation of experimental animals after NPBVAS implantation. Since May 2001, four long-term NPBVAS implant experiments in calves were performed. The blood gas and hemodynamic data were analyzed retrospectively. An additional prospective experiment was performed to confirm retrospective findings. All calves (n = 5) lived longer than 5 weeks without complication. In retrospective analysis, there was not a correlation between the O2 content and total blood flow in the pulmonary artery during the 1st postoperative week, but they began to correlate within the 2nd postoperative week. Then, there was a strong correlation after the 3rd postoperative week (r = 0.753). In the prospective experiment, O2 content related to total pulmonary flow after 2 weeks (r = 0.732) was the same as in the retrospective study. Most of the hemodynamic parameters studied became normalized after 14 days. In addition, easier controllability of the blood pumps was demonstrated after the 2nd postoperative week in all five experiments. Experimental results suggested that the native healthy heart accepted NPBVAS by reducing its cardiac output in 2 weeks. In addition, complicated control of the BPVAS was not necessary after 2 weeks of implantation. These results demonstrate the possibility of physiological adaptation to the NPBVAS being established within 2 postoperative weeks.

Hemolytic characteristics of oxygenators during clinical extracorporeal membrane oxygenation.

A connection was previously reported between the hemolytic characteristics associated with oxygenators and the pressure drop measurements in the blood chamber under experimental conditions simulating their use in cardiopulmonary bypass. We examined this association during extracorporeal membrane oxygenation (ECMO) conditions. Three oxygenators for ECMO or pediatric cardiopulmonary bypass (Menox EL4000, Dideco Module 4000, and Mera HPO-15H) were evaluated. Fresh blood from healthy Dexter strain calves anticoagulated with citrate phosphate dextrose adenine solution was used. The blood flow was fixed at 1 L/min, similar to that in ECMO. The Normalized Index of Hemolysis for Oxygenators (NIHO) has been modified according to the American Society of Testing and Materials standards, as was previously reported. The NIHO value was the lowest in the Menox (0.0070+/-0.0009) and increased from Menox to Dideco (0.0113+/-0.0099) to Mera (0.0164+/-0.0043); however, there were no significant differences among the oxygenators. This NIHO value has a close correlation to the pressure drop. In conclusion, this evaluation method is also applicable to comparison of the biocompatibility performance of different types of clinically available oxygenators for ECMO.

In vivo evaluation of the NEDO biventricular assist device with an RPM dynamic impeller suspension system.

Since 1995, the Baylor College of Medicine group has been developing the NEDO Gyro permanent implantable (PI) pump. The Gyro PI pump has achieved outstanding results up to 284 days with no thrombus formation during the left ventricular assist device (LVAD) animal experiments. However, in biventricular assist device (BVAD) animal experiments, thrombus formation did occur. An in vitro experiment showed the reason for thrombus formation was caused by the missed magnetic balance between the impeller and the actuator. On the basis of this result, the revolutions per minute (RPM) impeller suspension system was developed. Six long-term animal studies were performed in bovine models. Survival periods were 90, 80, 60, 51, 48, and 37 days, respectively. No thrombus was observed in the pumps with the exception of one right pump. In that experiment, the thrombus formation may have occurred when the pump had a low flow because of outflow kinking. In this article, the antithrombogenic effect of this RPM impeller suspension system will be discussed.

Preclinical evaluation of a new hollow fiber silicone membrane oxygenator for pediatric cardiopulmonary bypass: ex-vivo study.

Based on the results of many experimental models, a hollow fiber silicone membrane oxygenator applicable for long-term extracorporeal membrane oxygenation (ECMO) was developed. For further high performance and antithrombogenicity, this preclinical model was modified, and a new improved oxygenator was successfully developed. In addition to ECMO application, the superior biocompatibility of silicone must be advantageous for pediatric cardiopulmonary bypass (CPB). An ex vivo short-term durability test for pediatric CPB was performed using a healthy miniature calf for six hours. Venous blood was drained from the left jugular vein of a calf, passed through the oxygenator and infused into the left carotid artery using a Gyro C1E3 centrifugal pump. For six hours, the O2 and CO2 gas transfer rates were maintained around 90 and 80 ml/min at a blood flow rate of 2 L/min and V/Q=3, respectively. The plasma free hemoglobin was maintained around 5 mg/dl. These data suggest that this newly improved oxygenator has superior efficiency, less blood trauma, and may be suitable for not only long-term ECMO but also pediatric CPB usage.

Association of treatment with 15-deoxyspergualin and BK virus nephropathy in kidney allograft recipients.

OBJECTIVE: BK virus nephropathy (BKVN) has been proposed as an important cause of allograft dysfunction and loss in kidney allograft recipient over the last decade. Intense immunosuppression and tubular injury have been shown to promote the replication of polyomavirus. 15-deoxyspergualin (DSG), an effective immunosuppressive agent, is used as a rescue drug for acute rejection in clinical renal transplantation in Japan. To determine whether DSG is a risk factor for BKVN and outline the relationship among BKVN, DSG, and other risk factors, we analyzed 88 patients who received living-related renal transplantation between January 1999 and April 2003. METHODS: A total of 114 biopsy specimens from 88 living-related kidney transplantation recipients (performed between January 1999 to April 2003) were retrospectively analyzed. Patients received immunosuppression therapy based on calcineurin inhibitors and corticosteroid [tacrolimus (TAC) 33 and cyclosporin (CyA) 55]. Additionally, mycophenolate mofeteil (MMF) was used in 21 patients; DSG was used in seven patients; and anti-CD3 monoclonal antibody was used in 16 patients. We analyzed the degree of donor/recipient human leucocyte antigen (HLA) compatibility assessed by the number of HLA-A, -B, and -DR-mismatched antigens in 88 patients. The diagnosis of BKVN was made by the light microscopic examination and a positive immunohistochemical staining of anti-40 antibody in biopsy specimens. Patients were divided into two groups of group A (mild histological change) and group B (moderate or severe histological change) to determine the risk factors in different histological staging. The clinical course of two typical patients in different histological stage is described briefly to outline the risk factors of BKVN. RESULTS: We identified seven cases of BKVN (8.0%) from 88 transplanted patients. Significantly higher incidence of combination regimen consisting of TAC and MMF in BKVN group was noticed compared with non-BKVN group (57.1% vs. 9.9%; p = 0.003). BKVN was associated with a significantly higher incidence of DSG administration compared with non-BKVN group (57.1% vs. 3.7%; p

Factors predicting long-term graft survival after kidney transplantation: multicenter study in Japan.

A multicenter retrospective study was conducted in 936 living donor kidney transplant recipients treated with cyclosporine (CsA) or tacrolimus (FK) from April 1982. The influences of acute rejection, hyperlipidemia, and hypertension were estimated by Kaplan-Meier's analysis and Wilcoxon's analysis. Of 916 recipients, 532 (58.1%) had acute rejections. The 5- and 10-year graft survival rates in the recipients with acute rejection were 75.2% and 55.2%, respectively. The corresponding rates of the recipients without acute rejection were 80.2% and 70.6%, respectively. The graft survival rate was worse in recipients with late-phase rejection and multiple rejection episodes (p < 0.00006). Of 451 recipients, 176 (39.0%) had hypercholesterolemia 3 years after kidney transplantation. The 5- and 10-year graft survival rates in the recipients with hypercholesterolemia were 88.7% and 68.7%, respectively. Those of the recipients without hypercholesterolemia were 95.2% and 83.9%, respectively. The graft survival rate in the recipients with hypercholesterolemia was lower than that in the recipients without hypercholesterolemia (p = 0.003). Of 323 recipients, 123 (38.1%) had hypertriglyceridemia 3 years after kidney transplantation. The 5- and 10-year graft survival rates in the recipients with hypertriglyceridemia were 93.7% and 80.5%, respectively. Those in the recipients without hypertriglyceridemia were 95.1% and 86.5%, respectively. The graft survival rate in the recipients with hypertriglyceridemia was lower than that in the recipients without hypertriglyceridemia (p = 0.371). Of 367 recipients, 151 (41.1%) had systolic hypertension 3 years after kidney transplantation. The 5- and 10-year graft survival rates in the recipients with hypertension were 85.6% and 64.7%, respectively. Those of the recipients without hypertension were 95.6% and 83.8%, respectively. The graft survival rate in the recipients with hypertension was lower than that in the recipients without hypertension (p < 0.001). Acute rejection, hyperlipidemia (hypercholesterolemia and hypertriglyceridemia), and hypertension are predictive factors for long-term graft survival. Especially the onset time, number of rejections, and efficacy of treatment for acute rejection would have a significant influence on long-term graft survival.

Centrifugal blood pumps for various clinical needs.

During the past 10 years, different types of blood pumps were developed to address various clinical needs. The Nikkiso centrifugal blood pump was developed for cardiopulmonary bypass application. This blood pump has been widely used in Japan in more than 20% of the cardiopulmonary bypass procedures. The Kyocera C1E3 Gryo pump was developed for short-term circulatory assistance and extracorporeal membrane oxygenation application for up to 2 weeks. This blood pump has been clinically used for up to 28 days without any blood clot formation. Through Phase I of the Japanese government New Energy and Industrial Technology Development Organization (NEDO) program, a chronically implanted centrifugal pump for left ventricular assistance was developed. This pump has already demonstrated its effectiveness, safety, and durability as a 2 year blood pump through in vitro and in vivo experiments. Currently, it is in the process of being converted from an experimental to a clinical device. Through Phase II of the NEDO program, a permanently implantable biventricular assist centrifugal blood pump system is under development. It has demonstrated that the previously mentioned left ventricular assist device blood pump is easily converted into a right ventricular assist pump by simply adding a spacer between the pump and the actuator. This communication discusses the historical development strategies for centrifugal blood pumps and their current status for different clinical needs.

Combination of therapeutic apheresis and therapeutic ventricular assistance for end-stage heart failure patients.

Dilated cardiomyopathy is a cardiac disease of unknown origin which is characterized by the gradual development of cardiac failure associated with four-chamber dilatation of the heart. Heart transplantation has been considered as the last resort for this disease. However, some patients who received support with a ventricular assist device (VAD) as a bridge-to-transplantation and then recovered without transplantation have been reported. This new concept of treating heart failure is termed bridge-to-recovery. A VAD can inhibit the heart failure compensatory mechanisms by extreme ventricular unloading. Also, heart failure is a complex neurohormonal/autocrine-paracrine syndrome, and these mechanisms consecutively lead to inflammatory response by proinflammatory cytokines; interleukin-1 alpha (IL-1 alpha), interleukin-1 beta (IL-1 beta), interleukin-2 (IL-2), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha). Furthermore, the existence of anti-beta1-adrenoceptor autoantibodies (A-beta1-AABs) in a patient with dilated cardiomyopathy has been reported. These proinflammatory cytokines and this antibody accelerate a ventricular remodeling and a contractile dysfunction over the long term. Apheresis can also inhibit the vicious cycle in heart failure by removing the factors that are produced by activated neurohormonal/autocrine-paracrine compensatory mechanisms. Therefore, we propose that the combined therapies, therapeutic VAD and therapeutic apheresis, will provide a prominent outcome for a patient who is suffering from end-stage heart failure.

Assessing the calf pulmonary function during a long-term biventricular assist device study with a centrifugal blood pump.

Pulmonary congestion due to inappropriate pump flow management is one major problem necessary to avoid during long-term biventricular assist device (BVAD) implantation. Our objective was to assess the effects of pulmonary arterial flow rate and flow rates of both (right and left) bypass pumps. Six healthy calves, which had been implanted with a BVAD system, were selected for this retrospective study. Pulmonary artery flows, both pump flow rates, oxygen saturation of the arterial blood, and pulmonary arterial pressures were assessed as parameters of pulmonary function as was routine clinical evaluation of respiratory rate and character and chest auscultation. The average pulmonary artery flow rate (PAF), systolic pressure of pulmonary artery (sPAP), and oxygen saturation were 148.8 ml/kg per min, 35.1 mm Hg, and 95.3%, respectively. Pulmonary dysfunction occurred in one case, in which the mean PAF, sPAP, and oxygen saturation were 169 ml/kg per min, 66.1 mm Hg, and 90.9%, respectively. The ratio for the right/left pump flow rate (R/L ratio) for the case having pulmonary dysfunction was 1.57 even though the ratio for the other cases was less than 1. Maintaining an R/L ratio less than 1 and/or PAF less than 160 ml/kg per min and PAP less than 50 mm Hg is recommended as the initial conditions to target to avoid pulmonary dysfunction during a BVAD implantation with a beating heart condition.

Titania gel reduces thrombin generation.

Titanium alloy (Ti) commonly is used for long-term blood pumps as a conventional blood contacting material. Thrombus formation in the pump, however, is still a critical problem. Once thrombin is generated on the Ti surface, it activates platelets and the coagulation cascade, leading to thrombus formation. It would be expected that an inhibition of thrombin generation on a blood-contacting surface would prevent thrombus formation. In this study, the titania gel (Ti-gel) on the surface of Ti was formed with chemical modification. The surface structure and its effects on the coagulation cascade were evaluated. Scanning electron microscopic study revealed numerous cracks on the dried surface of Ti-gel, indicating a water-enriched layer. Blood coagulation on the Ti-gel was less than that on the Ti. Generated thrombin on the Ti-gel was less than that on the Ti in both the extrinsic and intrinsic pathways. There was no statistical difference of thrombin degradation. These results suggest that coagulation cascade on the Ti surface was inhibited by the Ti-gel formation. The Ti-gel may have better antithrombogenic characteristics for blood pumps because of its antiblood-coagulation effects.

Flow visualization study to investigate the secondary flow behind the impeller in the Gyro centrifugal pump.

The Gyro permanently implantable pump consists of a sealless pump housing and an impeller supported with a double pivot bearing. The secondary vanes are attached to increase the secondary flow to avoid thrombus formation behind the impeller. Flow visualization studies using an oil film method were performed on three types of impellers: no secondary vanes, 0.5 mm height secondary vanes, and 1.0 mm height secondary vanes. Comparison studies of these impellers were performed on the surfaces of the impeller bottom and bottom housing. Regarding the surface of the impeller bottom, the impeller with no secondary vanes had the least stagnant areas around the shaft. On the other hand, the impeller having 1.0 mm height secondary vanes had the most distinguished flow lines on the bottom housing. Overall, the impeller secondary vanes with a height of 0.5 mm (current design) seemed to create the most effective secondary flow.

Centrifugal blood pump with a hydraulically-levitated impeller for a permanently implantable biventricular assist device.

A permanently implantable biventricular assist device (BVAD) system has been developed with a centrifugal pump which is activated by a hydraulically-levitated impeller. The pump impeller floats hydraulically into the top contact position; this position prevents thrombus formation by creating a washout effect at the bottom bearing area, a common stagnant region. The pump was subjected to in vitro studies using a pulsatile mock circulation loop to confirm the impeller's top contact position and the swinging motion produced by the pulsation. Eleven in vivo BVAD studies confirmed that this swinging motion eliminated blood clot formation. Twenty-one pumps im-planted for up to three months did not reveal any thrombosis in the pumps or downstream organs. One exception was a right pump which was exposed to severe low flow due to the kinking of the outflow graft by the accidental pulling of the flow meter cable. Three ninety-day BVAD studies were achieved without thrombus formation.