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Biomedical subjects

Tomohiro Mizuno

Publications and source records attributed to Tomohiro Mizuno.

15 recordsLinked to original sources

On-pump beating-heart mitral valve plasty without aortic cross-clamping.

Patients with ischemic cardiomyopathy often have mitral regurgitation, which should be corrected for better long-term survival. Mitral valve surgery is usually performed during cardiopulmonary bypass under the arrested heart condition. The ascending aorta is cross-clamped and the heart is arrested using a cardioplegic solution. However, because ischemic cardiomyopathy patients often have a severely atherosclerotic ascending aorta and low cardiac function, aortic cross-clamping and cardiac arrest increase the risk of postoperative thromboemboli and low cardiac output syndrome. Under the on-pump beating-heart condition, we performed mitral valve plasty concomitant with coronary artery bypass grafting, tricuspid annuloplasty, left ventricular aneurysmectomy, and the maze procedure without aortic cross-clamping for a patient with ischemic dilated cardiomyopathy and bradycardial atrial fibrillation. The patient had no postoperative complications and re covered rapidly. Thus, to prevent serious postoperative complications, on-pump beating-heart mitral valve surgery without aortic cross-clamping may be a suitable surgical option for patients with ischemic cardiomyopathy.

Aged↗

Elastin stabilizes an infarct and preserves ventricular function.

BACKGROUND: After a myocardial infarction, the injured region becomes fibrotic and the myocardial scar may expand if the ventricular wall lacks elasticity. Cardiac dilatation may precipitate the vicious cycle of progressive heart failure. The present study evaluated the functional benefits of increasing elastin within a myocardial scar using cell based gene therapy. METHODS AND RESULTS: A myocardial infarction was generated by ligation of the left anterior descending artery in rats. Six days later, 2 x 10(6) syngeneic rat endothelial cells transfected with the rat elastin gene (elastin group, n=14) or an empty plasmid (control group, n=14) were transplanted into the infarct scar. Cardiac function, left ventricular (LV) volume, and infarct size were monitored over 3 months by echocardiography, Langendorff measurements, and planimetry. Elastin deposition was evaluated in the cells and in the infarct region by Western blot assay and by histological examination. Recombinant elastin was found in the scar in the elastin group but not the control group during the 3 months after cell transplantation. Histological assessment demonstrated organized elastic fibers within the infarct region. LV volume and infarct size were significantly smaller (P<0.05) in the elastin group than in the control group. Cardiac function evaluated by echocardiography and during Langendorff perfusion was significantly better (P<0.05) in the elastin group than in the control group. CONCLUSIONS: Expressing recombinant elastin within the myocardial scar reduced scar expansion and prevented LV enlargement after a myocardial infarction. Altering matrix remodeling after an infarct preserved the LV function for at least 3 months.

Animals↗

Overexpression of elastin fragments in infarcted myocardium attenuates scar expansion and heart dysfunction.

Ventricular dilation after myocardial infarction can cause heart failure. Increasing strength and elasticity in the infarct region might prevent ventricular dilation. Because elastin provides strength, extensibility, and resilience to tissues and maintains tissue architecture, we studied the effect of elastin expression in the infarct on scar expansion and heart function. COS-7 cells transfected with a plasmid with an elastin gene fragment or a vector were seeded into a Gelfoam mesh and cultured. Mechanical stretch test (n = 5/group) showed that the elastin mesh was more elastic (P < 0.05) and tensile (P < 0.05) than the vector mesh. In an in vivo study in rats, 6 days after left anterior descending coronary artery ligation, COS-7 cells (Cell group, n = 7) or COS-7 cells with elastin gene (Elastin group, n = 9) or vector (Vector group, n = 9) were transplanted into the infarct; infarcted rats served as controls (n = 7). Over 8 wk the Cell group did not demonstrate effects on scar expansion and deterioration of heart function vs. controls. In contrast, infarct expansion was smaller and heart function was better maintained in the Elastin group vs. the Vector group (P < 0.05). At 8 wk after cell transplantation Langendorff data showed that the Elastin group had greater (P < 0.01) developed pressure and a smaller left ventricular volume than the Vector group. Western blot and histology showed accumulated elastin in the Elastin group infarct. Changing the extracellular matrix composition of a myocardial infarct by increasing elastin fragment content attenuated scar expansion, ventricular dilation, and onset of heart dysfunction.

Animals↗

Oral cibenzoline reduces postoperative atrial fibrillation in coronary artery bypass grafting.

OBJECTIVE: The objective of the present study was to investigate the effectiveness of postoperative oral administration of cibenzoline for the prevention of atrial fibrillation (AF) in coronary artery bypass grafting (CABG). METHODS: A total of 39 patients who underwent isolated CABG from September 2000 to February 2001 and who took oral cibenzoline (300 mg per day for 10 days beginning immediately after surgery) were compared to 59 patients who underwent surgery in our department 8 months prior to the study and who did not take cibenzoline for incidence of postoperative AF. Exclusion criteria encompassed age (>80 years), low ejection fraction (<30%), high serum creatinine level (>2.0 mg/dL), and history of supraventricular arrhythmia with or without treatment by anti-arrhythmic drugs. RESULTS: Postoperative AF occurred in 2 patients in the cibenzoline group (2/35, 5.7%) and 20 patients in the control group (20/59, 33.9%). There were significant differences in the incidence of postoperative AF (p = 0.002). Multivariate analysis revealed that the administration of cibenzoline reduced the incidence of AF significantly, and that a large number of bypass grafts significantly contributed to postoperative AF in CABG. The number of bypass grafts was significantly larger in the cibenzoline group, indicating that cibenzoline administration significantly suppresses the incidence of AF after CABG in high-risk patients. CONCLUSIONS: Postoperative administration of oral cibenzoline for 10 days is one effective method for the prevention of AF after CABG.

Administration, Oral↗

Reloading the heart: a new animal model of left ventricular assist device removal.

OBJECTIVES: Left ventricular assist devices are proposed as a bridge to recovery, but recurrent ventricular deterioration has limited this approach. We describe a new animal model that simulates the effects of left ventricular assist device unloading and then reloading after device removal. The model might facilitate the evaluation of interventions intended to prevent recurrent ventricular dysfunction. METHODS: The hearts and lungs of Lewis rats were removed and transplanted into the abdomen of recipient rats by anastomosing the donor's ascending aorta to the recipient's abdominal aorta. The transplanted hearts were maintained unloaded for 2 weeks in 49 animals. Eighteen transplanted hearts were removed after 2 weeks of unloading. In 17 animals the donor's right pulmonary artery was anastomosed to the recipient's abdominal aorta to reload the heart for an additional 2 weeks. In 14 animals the hearts were maintained unloaded for 4 weeks (an additional 2 weeks). The unloaded and reloaded hearts were compared with normal rat hearts (n = 18). RESULTS: In the unloaded hearts the left ventricular end-diastolic pressures remained low. The left ventricular systolic pressures were lower than the aortic pressures. The left ventricular weights (n = 8) and volumes (n = 4) remained significantly lower ( P < .01) than in the normal hearts. Two weeks after reloading, the left ventricular end-diastolic pressure (n = 8) increased ( P < .01), and the ventricle ejected. The left ventricular systolic pressures exceeded the aortic pressures. The left ventricular weights and volumes increased ( P < .01) and approached those of normal hearts. Matrix metalloproteinase 9 (n = 6/group) levels decreased in the unloaded state ( P = .02) and increased back to normal values after reloading. CONCLUSIONS: This surgical model simulated left ventricular assist device unloading of the left ventricle. The second operation reloaded the left ventricle, which then enlarged. This model will permit the evaluation of adjunctive interventions, such as cell transplantation, intended to facilitate successful left ventricular assist device removal and prevent recurrent dilatation.

Anastomosis, Surgical↗

Disposable magnetically levitated centrifugal blood pump: design and in vitro performance.

A magnetically levitated (MagLev) centrifugal blood pump (CBP) with a disposable pump head has been designed to realize a safe, easy-to-handle, reliable, and low-cost extracorporeal blood pump system. It consisted of a radial magnetic-coupled driver with a magnetic bearing having a two-degree freedom control and a disposable pump head unit with a priming volume of 24 mL. The easy on-off disposable pump head unit was made into a three-piece system consisting of the top and bottom housings, and the impeller-rotor assembly. The size and weight of the disposable pump unit were 75 mm x 45 mm and 100 g, respectively. Because the structure of the pump head unit is easily attachable and removable, the gap between the electromagnets of the stator and the target material in the rotor increased to 1.8 mm in comparison to the original integrated bearing system of 1.0 mm. The pump performance, power requirements, and controllability of the magnetic bearing revealed that from 1400 to 2400 rpm, the pump performance remained fairly unchanged. The amplitudes of the X- and Y-axis rotor oscillation increased to +/- 24 microm. The axial displacement of the rotor, 0.4 mm, toward the top housing was also observed at the pump rpm between 1400 and 2400. The axial and rotational stiffness of the bearing were 15.9 N/mm and 4.4 Nm/rad, respectively. The MagLev power was within 0.7 Watts. This study demonstrated the feasibility of a disposable, magnetically suspended CBP as the safe, reliable, easy-to-handle, low-cost extracorporeal circulation support device.

Centrifugation↗

Double-patch technique for postinfarction ventricular septal perforation.

A modified infarct-exclusion technique for postinfarction ventricular septal perforation is presented. The perforation is closed directly by a small patch next to the conventional patch, and biological glue is applied between the patches to induce stable polymerization. The patch stuck to the infarcted septum, and no residual shunt was observed in any patient because the wide adhesion prevents excessive pressure on the suture line. Seven of 9 patients in whom this method was used had good results. This technique appears suited for repair of ventricular septal perforations, especially those with extensive fresh infarction.

Cardiac Surgical Procedures↗

Transaortic stented graft implantation for aortic arch aneurysm. Its benefits and risk.

OBJECTIVES: Despite steady improvements, surgery for aortic arch disease, including the distal arch, continues to result in high rates of morbidity and mortality. We have performed aortic arch repair using a transaortic stented graft implantation into the descending aorta in 8 patients who had true aortic arch aneurysms, and here have reviewed the efficacy and problems from this procedure. METHODS: Six patients underwent transaortic stented graft implantation into the descending aorta with bypass to the arch vessels. The other two underwent stented graft implantation into the descending aorta with replacement of the ascending aorta and aortic arch. One patient had a ruptured aneurysm. RESULTS: Each operation was performed via a median sternotomy without left thoracotomy. There was no new postoperative occurrence of left recurrent laryngeal nerve palsy. All the five patients without perioperative neurological complication could be extubated within 24 h after surgery. In each case, postoperative enhanced computed tomography scans showed successful thromboexclusion of the aneurysm. There was no endoleak and no graft migration. One patient suffered cerebral injury. Spinal cord injury occurred in 2 patients, and this serious complication may have been caused by prolonged ischemia in the lower body and the long stented graft. CONCLUSIONS: This surgical strategy was effective for arch aneurysm and produced less damage than a conventional procedure to the postoperative respiratory function, while the operative technique need to be improved to decrease the frequency of brain and spinal cord injury.

Aged↗

Biventricular pacing with coronary bypass and Dor's ventriculoplasty.

We applied biventricular pacing to a patient with severe ischemic dilated cardiomyopathy (left ventricular [LV] ejection fraction 19%, LV end-diastolic volume 360 mL, and complete left bundle branch block). An epicardial LV lead was surgically implanted concomitant with on-pump beating coronary artery bypass grafting and Dor's endoventricular circular patch plasty. Biventricular pacing immediately achieved the resynchronization of the LV contraction, and improved cardiac function as well as reducing mitral regurgitation. Biventricular pacing combined with cardiac surgery for patients with cardiomyopathy and complete left bundle branch block may produce beneficial effects on LV function.

Aged↗

Mural thrombus generation in type 2A and 2B von Willebrand disease under flow conditions.

To explore the mechanisms that underlie the bleeding tendency in type 2A and 2B von Willebrand disease (VWD), we analyzed the mural thrombus generation process on a collagen surface under physiologic blood flow in a perfusion chamber using whole blood from these VWD patients. At a low shear rate (50 s(-1)), thrombus generation in all type 2A and 2B VWD patients was comparable to that of healthy controls. At a high shear rate (1500 s(-1)), thrombus generation was impaired in all type 2A patients, whereas that in type 2B VWD patients varied from normal to significantly defective, as judged by epifluorescence microscopy of thrombus surface coverage. However, in type 2B patients who showed normal thrombus generation at 1500 s(-1), the height and volume of thrombi was significantly reduced, albeit with the normal surface coverage, compared with control thrombi, and von Willebrand factor (VWF) was poorly distributed within the type 2B thrombus mass when analyzed in detail by confocal laser scanning microscopy. Addition of purified VWF to patient blood completely reversed the defective spatial thrombus growth in type 2B VWD. Thus, our results confirm the impaired thrombus generation in type 2B VWD, which has never been demonstrable in previous in vitro soluble-phase platelet aggregation assays, and point to the critical function of larger VWF multimers in the proper spatial growth of mural thrombi under high shear rate conditions.

Blood Coagulation↗

Distinct and concerted functions of von Willebrand factor and fibrinogen in mural thrombus growth under high shear flow.

Using a perfusion chamber and confocal laser scanning microscopy, we analyzed the interplay of von Willebrand factor (VWF) and fibrinogen during thrombus growth on a collagen surface under physiologic high shear rate conditions. During initial thrombogenesis, platelet thrombi were constructed totally by VWF, not by fibrinogen. Fibrinogen accumulated predominantly inside the growing thrombi as a function of time, whereas the thrombus surfaces directly exposed to flow were occupied constantly by VWF throughout the observation period. In perfusion of afibrinogenemia (AF) blood lacking both plasma and platelet fibrinogen, the final height and volume of thrombi were significantly reduced compared with controls, albeit the area of surface coverage was normal. The impaired thrombus growth in AF was only partially corrected by the addition of purified fibrinogen to AF blood, whereas the addition of purified VWF to blood of severe von Willebrand disease (VWD) completely normalized the defective thrombus growth in this disease. Thus, the initial 2-dimensional thrombus expansion involves only VWF, whereas the time-dependent accumulation of fibrinogen, released from activated platelets, acts as a core adhesive ligand, increasing thrombus strength and height and resulting in 3-dimensional thrombus development against rapid blood flow.

Afibrinogenemia↗

Platelet shape changes and adhesion under high shear flow.

Recent studies have revealed that the platelet adhesive process under flow is tightly regulated by multiple ligand-receptor interactions. However, platelet morphological changes during this process, particularly its physiological relevance, remain unknown under blood flow conditions. Using epifluorescence and scanning electron microscopy, we evaluated the real-time changes in platelet morphology during a platelet adhesive process on a von Willebrand factor-coated surface under physiological high shear flow in a perfusion chamber. Here, we show that dynamic platelet shape changes occurring during distinct phases of the adhesive process are precisely regulated by "inside-out" and "outside-in" integrin signals and are also a key regulatory element in successful platelet thrombogenesis opposing rapid blood flow in vivo.

Androstadienes↗

Temporary and permanent biventricular pacing via left ventricular epicardial leads implanted during primary cardiac surgery.

OBJECTIVES: Biventricular pacing (BVP) is a new strategy for treating patients with severe congestive heart failure (CHF) and intraventricular conduction delay, but its full potential and technicalities of BVP require further evaluation. We evaluated BVP benefits in 4 patients in whom we implanted a left ventricular lead during primary cardiac surgery. METHODS: Four CHF patients treated surgically between October 2000 and August 2001 underwent, at primary surgery, the implantation of leads in the right atrium, right ventricle, and left ventricle (LV) for postsurgical BVP. All patients had severe LV dysfunction and dilatation with intraventricular conduction delay. Surgeries involved CABG alone (n = 1), CABG + Dor's operation (n = 2), and tricuspid valve replacement + Maze procedure (n = 1). BVP was begun immediately after surgery in all 4 patients. Hemodynamic variables with BVP were compared to those without BVP for each patient, and the utility and technical aspects of implantation were evaluated. RESULTS: BVP increased mean systemic blood pressure by 11% and mean LV stroke work index by 19% in the acute postsurgery period, and reduced mitral regurgitation. Two of the patients were implanted with a generator for permanent BVP, one at 1 month and the other at 6 months after surgery. The threshold of the LV epicardial lead of these 2 patients was below 2 V during follow-up, and BVP was successful. CONCLUSIONS: Temporary BVP during the short-term after cardiac surgery improved cardiac function and decreased mitral regurgitation in all 4 of our patients. Epicardial lead implantation may thus be a useful option during surgical treatment of patients with CHF and intraventricular conduction delay if long-term permanent BVP is indicated.

Aged↗

Stented elephant trunk procedure combined with ascending aorta and arch replacement for acute type A aortic dissection.

OBJECTIVES: Despite steadily improving outcomes, surgery for acute type A aortic dissection has several unresolved problems such as expansion of the residual false lumen in the descending aorta. We performed transaortic stented graft implantation into the descending aorta combined with the ascending aorta and aortic arch replacement for acute type A aortic dissection. We review the efficacy and outcomes of this procedure with respect to the residual false lumen and postoperative neurologic complications we encountered. METHODS: Nine consecutive patients with acute type A aortic dissection underwent this procedure. The stented elephant trunk graft was implanted through the aortic arch under hypothermic circulatory arrest. The stented graft was 15 cm long in six patients, and 10 cm long in three patients. Enhanced computed tomography (CT) was performed 1 month after surgery and once each year after discharge to evaluate the postoperative time course of the residual false lumen. RESULTS: Cardiopulmonary bypass (CPB) time was quite long because of slow cooling and re-warming [352+/-92 (mean+/-SD) min], and average lower-body arrest time was 54+/-10min. The intima in one patient was injured at the time of implantation, and a small leak was created. One patient died of multiorgan failure postoperatively. One patient suffered cerebral injury, and two suffered spinal cord injury perioperatively. Average follow-up time was 40.4 months (range, 13-66 months). One patient died of cerebral infarction during follow up, and the other seven survived and remain well. Postoperative enhanced CT scans showed that the dissected descending aortas attached to the stented grafts and the aortas near the stented grafts returned to normal. In one patient with no re-entry, the false lumen completely closed with thrombi and the entire aorta returned to normal. The diameter of the descending aorta decreased or did not change in six of the seven patients (85.8%) and increased by only 2mm in one of them (14.2%) during follow up. CONCLUSIONS: Implantation of a stented elephant trunk into the descending aorta combined with replacement of the ascending aorta and total arch for acute type A aortic dissection is effective in closing the residual false lumen of the descending aorta and in preventing expansion of the descending aorta. However, further technical modifications, such as using a short stented elephant trunk, eliminating aortic clamping, shortening CPB and spinal cord ischemic time, and reconstruction of left subclavian artery, are needed to prevent neurologic complications.

Acute Disease↗

One piece ultracompact totally implantable electromechanical total artificial heart for permanent use.

An ultracompact, one piece, totally implantable electromechanical total artificial heart (TAH) has been developed as a permanent replacement for failing hearts. It consists of left and right pusher plate blood pumps (stroke volume 55 ml) made of titanium alloy (Ti-6Al-7Nb) sandwiching a miniaturized electromechanical actuator between them. The diameter of the TAH is 90 mm, with a thickness of 70 mm, yielding an overall volume of 400 ml. It weighs 450 g. Although it is miniaturized, it provided a maximum pump output of 8 L/min against a left afterload of 100 mm Hg. It required approximately 12 watts to provide a pump output of 6.5 L/min with maximum efficiency of 13.5%. To balance left and right flow, the right stroke length was made 10% shorter than the left, and an auxiliary compliance chamber was used to compensate for additional flow differences between them. Motor commutation pulses and a Hall effect pusher plate sensor signal were used in the controller to implement the left master alternate variable rate mode. The calf fitting study revealed excellent anatomic compatibility, and the first successful survivor was obtained in December 2001. Studies of system endurance and biocompatibility are required to ensure long-term reliability. This TAH is promising for permanent replacement of the failing heart as well as for bridge to heart transplantation for the smaller size group of end-stage cardiac patients.

Animals↗