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Biomedical subjects

Y Sawa

Publications and source records attributed to Y Sawa.

At least 91 records · Page 5Linked to original sources

Pulmonary blood flow distribution after the total cavopulmonary connection for complex cardiac anomalies.

In total cavopulmonary connection (TCPC), the anastomotic portion of the caval veins to the pulmonary artery (PA) is decided empirically based on personal experience. To compare the pulmonary flow distribution from both caval veins in various types of cavopulmonary anastomosis, intrapulmonary ventilation-perfusion distribution after TCPC was studied using lung scanning. We studied 11 patients, 2 to 37 years old, at 30-84 months after TCPC. Lung scanning was performed by administering 185 MBq of xenon-133 saline solution from their upper extremities and, after xenon-133 was washed out, from their lower extremities. Radionuclide counts on both lungs were obtained and intrapulmonary ventilation-perfusion distribution was assessed. In 4 patients whose superior vena cava (SVC)-PA anastomosis was on the right side of the inferior vena cava (IVC)-PA anastomosis, the blood flow distribution of the right and left lungs was 57.4%: 42.6%. In 3 patients whose SVC-PA anastomosis was on the left side of the IVC-PA anastomosis, the blood flow distribution of the right and left lungs was equal in both lungs (right, 53.1%; left, 46.9%). Systemic arterial oxygen saturation increased after TCPC (before TCPC, 85.3% +/- 2.7% and after TCPC, 89.8% +/- 2.3% (P < 0.05) in group R; before TCPC, 86.1% +/- 2.8% and after TCPC, 93.6% +/- 0.6% (P < 0.02) in group L). After TCPC, the value in group L had a tendency to be greater than that in group R (P < 0.04), in spite of the same values of systemic arterial oxygen saturation before TCPC and cardiac index (group R, 2.9 +/- 0.96; group L, 3.4 +/- 0.37). Lung scanning with xenon-133 revealed the distribution of pulmonary blood flow in the patients after TCPC quantitatively, and in the patients whose SVC-PA anastomosis was on the left side of the IVC-PA anastomosis, the right and left balance of the pulmonary blood flow distribution appeared to be more balanced compared with patients whose connection was done the opposite way.

Adolescent↗

The effects of a new ultra-short-acting beta-adrenergic blocker, ONO-1101, on cardiac function during and after cardiopulmonary bypass.

The administration of an ultra-short-acting beta-adrenergic antagonist, esmolol, has been introduced as a novel method for beating-heart surgery. In the present study, a new ultra-short-acting beta-blocker, ONO-1101, was administered during cardiopulmonary bypass (CPB) to investigate its effects on cardiac function and hemodynamics. Nine adult mongrel dogs underwent 60 min of CPB during which they were given either ONO-1101 (ONO group; n = 4) or saline (control group; n = 5). In the ONO group, the hearts became flaccid enough for surgery to be performed without cardiac standstill within 10 min after the commencement of ONO-1101 with significant decreases in the heart rate, the preload recruitable stroke work (PRSW), and the slope of the end-systolic left ventricular pressure-volume relationship (Emax). The mean arterial pressure and systemic vascular resistance also decreased, but were maintained above 50 mmHg during CPB without catecholamine. These indices increased to the control group level 20 min after the discontinuation of ONO-1101. The serum concentration of ONO-1101 decreased from the maximum level of 121 +/- 15 microg/ml soon after infusion to 11 +/- 5 microg/ml within 30 min after discontinuation. These data suggest that ONO-1101 may be useful to enable beating-heart surgery to be performed without aortic cross-clamp as an ultra-short-acting beta-adrenergic blocker.

Adrenergic beta-Antagonists↗

First brain dead donor heart transplantation under new legislation in Japan.

The first heart transplantation was carried out in Japan successfully, after the brain death and organ transplantation law was settled in 1997. The recipient patient was a 47-year-old man with the dilated phase of hypertrophic cardiomyopathy who had been on a Novacor implantable left ventricular assist system for the previous 4 months. Since the donor hospital was about 200 km from the recipient hospital which took approximately 2 hours for transportation, the total ischemic time was 3 hours and 24 minutes. The post-transplant course was smooth, and the patient was discharged on postoperative day 75.

Brain Death↗

Clinical role of blood heparin level monitoring during open heart surgery.

Protamine has been used for neutralizing heparin and its dosage is decided by the initial fixed dose of heparin. Adequate protamine neutralization is very important to reduce complications. To attenuate excess reactions, in particular, whole blood heparin concentration during and after cardiopulmonary bypass was measured using Hepcon, and the efficacy of optimal protamine dose in open heart surgery was evaluated. Twenty patients were randomly divided into two comparable groups, P and C. In the C group, heparin was neutralized with an initial fixed dose of protamine, 1.67 mg protamine per milligram total heparin (n = 8). In the P group, protamine dose was determined for residual heparin concentration (n = 12). In the P group, blood heparin concentrations at 60 minutes after the establishment of cardiopulmonary bypass, just after cardiopulmonary bypass and first protamine administration were 2.35 +/- 0.14, 2.31 +/- 0.17 and 0.13 +/- 0.08 U/ml, respectively. Concentrations reached zero with the second protamine administration. The requirement of transfusion (659 +/- 224 vs. 1559 +/- 323 ml, p = 0.0314), pulmonary vascular resistance index just after the protamine administration (190 +/- 22 vs. 286 +/- 18 dyne.s.cm-5.m2, p = 0.0137) and the IL-8 levels (just after protamine: 26.9 +/- 5.1 vs. 43.5 +/- 5.9 pg/ml, p = 0.0499, 12 hours after cardiopulmonary bypass: 37.1 +/- 12.1 vs. 86.8 +/- 20.0, p = 0.0435) in the P group were significantly lower than those in the C group. These data suggested that heparin level monitoring in whole blood may be useful to determine the optimal dose of protamine resulting in the decrease of a requirement of blood components in open heart surgery and attenuating in transient pulmonary hypertension and excess protamine-induced inflammatory reactions.

Anticoagulants↗

Analysis of the elephant trunk method in patients with extensive thoracic aortic aneurysm.

We assessed the appropriate length of an elephant trunk prosthesis based on our experience with 9 patients experiencing extensive thoracic aneurysms. There were 3 patients with a true aneurysm, 5 patients with a dissecting aortic aneurysm, and 1 patient with a true plus dissecting aortic aneurysm. The subjects were 4 men and 5 women and, at the time of operation, were from 38 to 74 years old. The second-stage operations were performed on 6 patients from 9 days to 6 months after the first-stage operation. In the first-stage operation, one patient died of pneumonia during the hospital stay and another died of multi-organ infarction after 15 months. In the second-stage operation, two patients died of brain hemorrhage in the chronic stage after the operation. The length of the elephant trunk prosthesis was 3 cm in the three early patients, and in one of them the elephant trunk could not be utilized due to its insufficient length. In the next three patients, the length was extended to 5 cm, but one of patient experienced an expansion of the aneurysm in the descending aorta due to a graft of insufficient length which could not decompress the aneurysmal wall. Therefore, in the last three patients, the length was further extended to 10 cm, and the second-stage operation was performed uneventfully on the 64th, 9th and 45th day, respectively after the first-stage operation within a continuous hospital stay. Neither expansion of the aneurysm nor thromboembolism was found during the waiting period for any of the second-stage operations. Accordingly, we recommend using a 10 cm elephant trunk prosthesis.

Adult↗

Helicobacter pylori-negative gastric and duodenal ulcers.

It is unclear whether Helicobacter pylori infection is essential to the development of peptic ulcers. In this study, we examined the rates of H. pylori-negativity among patients with peptic ulcers. We also attempted to clarify the characteristics of H. pylori-negative peptic ulcers to throw light on the pathogenesis of peptic ulcers. The study included 215 consecutive patients with gastric ulcers (GUs) and 120 consecutive patients with duodenal ulcers (DUs). After routine endoscopic examination and phenol red dye endoscopy, forceps biopsies were performed for culture, histology, and the rapid urease test. A patient was considered H. pylori-negative when the serum anti-H. pylori IgG and the three tests on biopsied specimens were all negative. H. pylori-negative rates were 3.2% in the patients with GUs and 1.7% in the patients with DUs. Lack of atrophy of the gastric mucosa was significantly more common in the H. pylori-negative patients with GUs. A history of ulcer disease was less common and antral ulcers were more common in H. pylori-negative GU patients, but not significantly so. As the urea breath test had not been performed, the possibility of a false-negative result cannot be completely ruled out, but we believe that the H. pylori-negative rate in our study is more reliable than these rates in previous reports, because we visualized H. pylori distribution by phenol red dye endoscopy to avoid false-negative results in biopsies, and we used both biopsy and serum anti-H. pylori IgG findings to establish an H. pylori-negative diagnosis. Since H. pylori-negative peptic ulcers certainly exist, H. pylori infection is thought not to be essential to the development of peptic ulcers. There were few differences between the characteristics of H. pylori-negative and H. pylori-positive peptic ulcers in our study. A large-scale study is required to clarify the characteristics of H. pylori-negative peptic ulcers.

Adult↗

The Freestyle stentless bioprosthesis for prosthetic valve endocarditis.

We report a case of methicillin-resistant Staphylococcus aureus-induced prosthetic valve endocarditis, which was successfully treated with aortic valve replacement using the Freestyle stentless bioprosthesis. The total root and stentless design of this bioprosthesis allows for more radical removal of infected tissue and easier treatment for annular abscess, while requiring less prosthetic materials than a conventional prosthesis. This bioprosthesis thus seems to be a valuable option for active endocarditis.

Abscess↗

Gene transfection of hepatocyte growth factor attenuates reperfusion injury in the heart.

BACKGROUND: Hepatocyte growth factor (HGF), a ligand for the c-Met receptor tyrosine kinase, plays a role as organotrophic factor for regeneration of various organs. HGF has an angiogenic activity and exhibits a potent antiapoptotic activity in several types of cells. Although HGF and the c-Met/HGF receptor are expressed in the heart, the role of HGF in the heart has remained unknown. METHODS: After we analyzed changes in expression of endogenous HGF and c-Met mRNA levels in the rat left ventricle after myocardial infarction, the human HGF gene in hemagglutinating virus of Japan (HVJ)-liposome was transfected into the normal whole rat heart. Three days after transfection, the heart was subjected to global warm ischemia and subsequent reperfusion, followed by assessment of its cardiac functions. RESULTS: Both HGF and c-Met/HGF receptor mRNAs were expressed in adult rat heart, and c-Met/HGF receptor mRNA was upregulated in response to myocardial infarction. HGF-transfected heart showed significant increase of human HGF protein level in the heart. Cardiac functions in terms of the left ventricular developed pressure, maximum dp/dt, and pressure rate product in hearts with HGF gene transfection were significantly superior to those in control hearts. In addition, leakage of creatine phosphokinase in the coronary artery effluent in hearts with HGF gene transfection was significantly lower than that in control hearts. CONCLUSIONS: These data indicated that both HGF and c-Met/HGF receptor mRNAs were upregulated in response to myocardial ischemic injury, and that HGF is likely to have a cytoprotective effect on cardiac tissue, presumably through the c-Met/HGF receptor.

Animals↗

Myocardial protection with endogenous overexpression of manganese superoxide dismutase.

BACKGROUND: Superoxide dismutase (SOD) is a potent candidate for myocardial protection against ischemia-reperfusion injury; however, its clinical significance by means of exogenous administration remains controversial. METHODS: To determine a role of endogenously overexpressed manganese SOD (Mn-SOD) in myocardial tolerance, rat hearts were transfected with Mn-SOD gene (group M) or no gene (group C) through intracoronary infusion of hemagglutinating virus of Japan (HVJ) liposome. Each group was divided into two subgroups to be subjected to ischemia-reperfusion using Langendorff apparatus with (subgroups M+ and C+) or without (M- and C-) administration of recombinant SOD. RESULTS: Mn-SOD overexpression was confirmed in M with ELISA, activity measurement, and immunohistochemistry. The highest recoveries of maximum and minimum dp/dt and the least creatine phosphokinase (CPK) leakage were observed in M+. These recoveries were higher in M- than in C- and C+. CONCLUSIONS: Thus, endogenous overexpression of Mn-SOD improved myocardial tolerance and its protective effect was enhanced by exogenous administration of SOD. These results suggest a possible strategy for myocardial protection with SOD: a combination of endogenous introduction through gene transfer with exogenous administration.

Animals↗

Selectin on activated platelets enhances neutrophil endothelial adherence in myocardial reperfusion injury.

OBJECTIVES: The glycoprotein P-selectin is an adhesion molecule that is rapidly expressed on the surface of platelets and endothelium during the inflammatory process. P-selectin on endothelium has been reported to play an important role in reperfusion injury. However, little is known regarding P-selectin on platelets in contributing to the pathophysiology of myocardial reperfusion injury. In this study, we hypothesized that P-selectin on platelets may enhance neutrophil endothelial adherence and this may play a role in neutrophil-mediated reperfusion injury. METHODS: Endothelial cells, cardiomyocytes, platelets and neutrophils were isolated from adult rats. Endothelial cells and cardiomyocytes were cultivated in a co-culture system. After exposure to hypoxia and reoxygenation, neutrophil adherence and migration were examined. RESULTS: After exposure to 6 h of hypoxia, endothelial cells co-incubated with platelets showed significantly greater neutrophil adherence (63.1 +/- 4.0%) and migration (78.2 +/- 6.7%) than endothelial cells alone (adhesion: 44.2 +/- 2.8%, migration: 57.9 +/- 4.9%). These increases were significantly inhibited (adhesion: 42.1 +/- 3.5%, migration: 65.5 +/- 3.8%) by an anti-P-selectin monoclonal antibody. Moreover, the superoxide-anion production was significantly elevated when activated platelets were added to neutrophils. This enhanced production was also inhibited by anti-P-selectin antibody. CONCLUSION: The presence of activated platelets enhanced neutrophil adhesion and migration process after hypoxia reoxygenation. This process may occur following platelet-neutrophil interactions via P-selectin and subsequent neutrophil activation.

Animals↗

Gene transfection of beta 2-adrenergic receptor into the normal rat heart enhances cardiac response to beta-adrenergic agonist.

BACKGROUND: Beta-adrenergic receptor system has a major role in cardiac contraction. If the receptor can be increased by gene transfection by means of intracoronary infusion of beta 2-adrenergic receptor to the hearts in which the receptor is down-regulated, this maneuver may improve the cardiac function and may be applied as one therapeutic approach during cardiopulmonary bypass or percutaneous cardiopulmonary support. METHODS AND RESULTS: The beta 2-adrenergic receptor complementary DNA was transfected in vivo to the normal rat heart by intracoronary infusion by means of a hemagglutinating virus of Japan liposome method, and the transfected heart was transplanted into the abdomen of another rat. Four days after transfection, the sarcolemma of the cardiomyocytes was well labeled by immunohistochemical labeling. Expression of beta-adrenergic receptor in the heart was approximately 4 times greater than that in control hearts (134 +/- 42 vs 33 +/- 4 fmol/mg protein) according to a ligand binding assay. The cardiac response of the transfected heart to isoproterenol was shown to be enhanced in a Langendorff perfusion system: after isoproterenol, developed pressure and maximal derivative of the left ventricle were greater than in the control heart (200 +/- 12 vs 174 +/- 6 mm Hg and 4110 +/- 130 vs 3491 +/- 255 mm Hg/sec), and the minimal derivative of the left ventricle was markedly smaller (-3040 +/- 267 vs -2528 +/- 131 mm Hg/sec). CONCLUSIONS: These results indicate that expression of beta 2-adrenergic receptor was approximately 4 times greater than in normal rat hearts by gene transfection using a hemagglutinating virus of Japan liposome method, and the transfected hearts demonstrated marked enhancements in cardiac response to beta-agonist, suggesting that transfer of this gene by intracoronary infusion has potential as a novel approach to enhance cardiac function.

Adrenergic beta-Agonists↗

Association of smooth muscle cell phenotypic modulation with extracellular matrix alterations during neointima formation in rabbit vein grafts.

PURPOSE: To clarify the mechanisms of structural changes underlying vein graft stenosis that limits efficacy of bypass grafting operation, we examined the accumulation and distribution of various extracellular matrix (ECM) components during neointima formation in rabbit vein grafts and analyzed their correlation with proliferation and phenotypic modulation of smooth muscle cells (SMCs). METHODS AND RESULTS: An autologous external jugular vein graft was transplanted into the carotid artery in 25 rabbits. After the restoration of blood flow, the graft was markedly dilated. Medial SMCs in the graft appeared to be injured, and they began to proliferate at day 4 and subsequently migrated and formed the neointima at day 7. The neointima observed at days 7 and 14 contained ECM components, including type I collagen, heparan sulfate, and chondroitin sulfate, and the intimal SMCs were phenotypically modulated from the differentiated-type (SM2-positive and SM embryonic-negative) to the dedifferentiated-type (SM2-negative and SM embryonic-positive) as determined with immunostainings for myosin heavy chain isoforms. The intimal SMC proliferation was maximal at 2 weeks and then decreased rapidly. However, the neointima continued to thicken thereafter throughout the 6-month period of the experiment, and ECM accumulation, such as type I collagen and decorin, a small dermatan sulfate proteoglycan, was a prominent feature observed in the hypocellular region of the deep intima from 2 months after the transplantation. The phenotype of the intimal SMCs gradually returned to the differentiated-type from the deep intima after 2 months, but a small number of the intimal SMCs remained in the dedifferentiated phenotype even at 6 months after the operation. CONCLUSION: The neointima in the vein graft was formed initially by means of migration and proliferation of the phenotypically modulated, dedifferentiated-type SMCs and continued to thicken by means of sustained ECM accumulation, including type I collagen and decorin, in association with the prolonged presence of the dedifferentiated-type SMCs. These chronologic features in cell kinetics and ECM accumulation may contribute to the frequent occurrence of graft wall thickening that occurs in the vein grafts.

Animals↗

Real time assessment of myocardial revascularization during coronary artery bypass surgery by means of ultrasonic integrated backscatter.

OBJECTIVE: The recovery of cyclic variation (CV) of ultrasonic integrated backscatter (IB) may provide a more sensitive predictor of the success of myocardial revascularization. This study was designed to elucidate the possibility of real time assessment of coronary artery bypass grafting (CABG) using CV of IB. METHODS: We studied 10 patients (61 +/- 4 years old) with the perfused areas by stenosed or occluded LAD without myocardial infarction. There were six ischemic dysfunctional areas, and four ischemic but non-dysfunctional areas. The CV of IB was measured before and just after extracorporeal circulation (ECC). Wall motion was analyzed by segmental wall thickening during systole at the same time of the IB analysis during CABG and at 3 weeks after CABG. Those 10 areas were completely revascularized. RESULTS: In the non-dysfunctional areas, wall thickening did not change and remained at normal values before and after ECC, and 3 weeks after CABG (31 +/- 3% 29 +/- 3% and 29 +/- 5%, respectively). The magnitude of CV of IB did not also change before and after ECC (8.0 +/- 1.6 dB and 7.8 +/- 1.3 dB). However, in the ischemic dysfunctional areas, while wall thickening did not change before and after ECC (21 +/- 5% and 20 +/- 5%), it increased and reached similar values as the non-dysfunctional regions at 3 weeks after CABG (26 +/- 7%, P < 0.01 vs. before and after ECC values). The magnitude of CV of IB increased even after ECC (3.71 +/- 0.4 dB vs. 7.4 +/- 3.5 dB, P < 0.05), and reached the same level as those in the non-dysfunctional areas. There was a significant relationship between wall thickening at 3 weeks after bypass grafting and magnitude of CV of IB after ECC (r = 0.67, P < 0.05). CONCLUSIONS: Improvement in wall motion was gradually attained after bypass grafting. On the contrary, an increase in the magnitude of CV of IB was obtained immediately after myocardial revascularization. Our data suggest that CV of ultrasonic IB method can provide close real time information regarding the effectiveness of bypass surgery.

Coronary Artery Bypass↗

Hepatocyte growth factor gene therapy of liver cirrhosis in rats.

Liver cirrhosis is the irreversible end result of fibrous scarring and hepatocellular regeneration, characterized by diffuse disorganization of the normal hepatic structure of regenerative nodules and fibrotic tissue. It is associated with prominent morbidity and mortality, and is induced by many factors, including chronic hepatitis virus infections, alcohol drinking and drug abuse. Hepatocyte growth factor (HGF), originally identified and cloned as a potent mitogen for hepatocytes, shows mitogenic, motogenic and morphogenic activities for a wide variety of cells. Moreover, HGF plays an essential part in the development and regeneration of the liver, and shows anti-apoptotic activity in hepatocytes. In a rat model of lethal liver cirrhosis produced by dimethylnitrosamine administrations, repeated transfections of the human HGF gene into skeletal muscles induced a high plasma level of human as well as enodogenous rat HGF, and tyrosine phosphorylation of the c-Met/HGF receptor. Transduction with the HGF gene also suppressed the increase of transforming growth factor-beta1 (TGF-beta1), which plays an essential part in the progression of liver cirrhosis, inhibited fibrogenesis and hepatocyte apoptosis, and produced the complete resolution of fibrosis in the cirrhotic liver, thereby improving the survival rate of rats with this severe illness. Thus, HGF gene therapy may be potentially useful for the treatment of patients with liver cirrhosis, which is otherwise fatal and untreatable by conventional therapy.

Animals↗