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Biomedical subjects

M Komeda

Publications and source records attributed to M Komeda.

At least 37 records · Page 2Linked to original sources

VCAM-1 expression precedes macrophage infiltration into subendothelium of vein grafts interposed into carotid arteries in hypercholesterolemic rabbits--a potential role in vein graft atherosclerosis.

Intimal hyperplasia and atherosclerosis are major causes of late vein graft failure after coronary artery bypass surgery. Hypercholesterolemia appears to be a key risk factor for atherosclerosis in vein grafts as well as in native arteries. We used a rabbit model of interposition jugular vein graft to the carotid artery and compared intimal thickening, macrophage accumulation, and VCAM-1 expression between hypercholesterolemic (H group) and normocholesterolemic (N group) rabbits. Fifty-nine rabbits were divided into H and N groups. Intimal thickening in vein grafts was approximately three times more prominent in the H group than in the N group. Macrophage accumulation progressively increased with time in H group vein grafts, although it was negligible in the N group. In the H group, moreover, macrophages were initially more abundant in deep intima, and subsequently accumulated in subendothelium of the grafted vein. VCAM-1 expression in luminal endothelial cells of the grafted veins was time-dependently increased after the vein graft surgery in both the H and N groups, and was more prominent in the H group. Comparison of the time-courses between macrophage accumulation and VCAM-1 expression revealed that VCAM-1 expression in luminal endothelium preceded subendothelial accumulation of macrophages. VCAM-1 expression and macrophage accumulation may be key factors which regulate progression of vein graft atherosclerosis.

Animals↗

Mutational analysis within the 3' region of the PKD1 gene in Japanese families.

Autosomal dominant polycystic kidney disease (ADPKD) is a widespread genetic disease that causes renal failure. One of the genes that is responsible for this disease, PKD1, has been identified and characterized. Many mutations of the PKD1 gene have been identified in the Caucasian population. We investigated the occurrence of mutations in this gene in the Japanese population. We analyzed each exon in the 3' single copy region of the gene between exons 35 and 46 in genomic DNA obtained from 69 patients, using a PCR-based direct sequencing method. Four missense mutations (T3509M, G3559R, R3718Q, R3752W), one deletion mutation (11307del61bp) and one polymorphism (L3753L) were identified, and their presence confirmed by allele-specific oligonucleotide (ASO) hybridization. These were novel mutations, except for R3752W, and three of them were identified in more than two families. Mutation analysis of the PKD1 gene in the Japanese population is being reported for the first time.

Alleles↗

Pericardial fluid as a new material for clinical heart research.

This article will review the results of recent clinical studies relating to the pericardial fluid in patients with various heart diseases. In ischemic patients, several angiogenic growth factors are accumulated in a high concentration in pericardial fluid. These may contribute to the angiogenesis and arteriogenesis, which are self-protecting mechanisms of myocardial ischemia. In congestive heart failure, natriuretic peptides are released into the pericardial fluid in a higher concentration compared with plasma levels. This suggests that these peptides may act as autocrine and/or paracrine factors. Pericardial fluid from ischemic patients induces cell proliferation and apoptosis depending on the cell type. Intrapericardial drug administration may provide a reasonable therapeutic strategy for heart diseases. In conclusion, the analysis of pericardial fluid appears to be a logical approach for elucidation of the pathophysiology of the heart.

Angiogenesis Inducing Agents↗

Left ventricular aneurysm repair in rats: structural, functional, and molecular consequences.

OBJECTIVES: This study examined the effects of aneurysm repair in a rat model of myocardial infarction on functional indices and on the spatiotemporal distribution of cardiac contractile protein and natriuretic peptide messenger RNA. METHODS: In a rat infarct model, expanded left ventricular aneurysms were plicated 4 weeks after infarction. At 30 weeks, transverse heart sections were taken at 4 levels (apex [level 1] through base [level 4]) and assessed by in situ hybridization histochemistry to determine regional messenger RNA levels of pre-pro-atrial natriuretic peptide, cardiac alpha-actin, skeletal alpha-actin, myosin light chain-2v, and beta-myosin heavy chain. RESULTS: Rats with plicated left ventricular aneurysms had reduced left ventricular endocardial circumference (19%, P <.005), lower heart weight ratio (31%, P <.05), left ventricular end-diastolic pressures (51%, P <.05), and increased +/-dP/dt (34%-38%, P <.05). Cardiac messenger RNA levels of pre-pro-atrial natriuretic peptide were reduced in the septum (levels 2 and 3), and skeletal alpha-actin levels were reduced in the septum and left ventricular free wall of plicated rats (level 3). beta-Myosin heavy chain levels were markedly reduced in peri-infarct regions of the left ventricular free wall, septum, and right ventricle in plicated rats at level 4, whereas myosin light chain-2v levels were reduced at levels 2 and 4 in the left ventricular free wall and at level 4 in the right ventricle. CONCLUSIONS: Plication of left ventricular aneurysm after infarction in the rat significantly reduced cardiac hypertrophy, improved cardiac function, and reduced the upregulation of pre-pro-atrial natriuretic peptide and both fetal and adult contractile protein isoforms associated with cardiac hypertrophy.

Actins↗

C-type natriuretic peptide induces redifferentiation of vascular smooth muscle cells with accelerated reendothelialization.

We recently reported that C-type natriuretic peptide (CNP) occurs in vascular endothelial cells and acts as a vascular-type natriuretic peptide. In the present study, we stimulated the cGMP cascade in proliferating smooth muscle cells (SMCs), in which particulate guanylate cyclase-B, the specific receptor for CNP, is predominantly expressed, by use of an adenovirus encoding rat CNP cDNA (Ad.CNP). In the Ad.CNP-treated cultured SMCs, CNP caused the growth inhibition of SMCs at G(1) phase with an early increase of p21(CIP1/WAF1) expression and subsequent upregulation of p16(INK4a). The expression of smooth muscle myosin heavy chain-2, which is the molecular marker of highly differentiated SMCs, was reinduced in the Ad.CNP-treated SMCs. The Ad.CNP-treated SMCs also reexpressed particulate guanylate cyclase-A, which shows high affinity to atrial and brain natriuretic peptide and is exclusively expressed in well-differentiated SMCs. CNP, which was overexpressed in rabbit femoral arteries in vivo at the time of balloon injury, significantly suppressed neointimal formation. Furthermore, an enhancement of the expression of smooth muscle myosin heavy chain-2 occurred in the residual neointima. In addition, early regeneration of endothelial cells was observed in the Ad.CNP-infected group. Thus, stimulation of cGMP cascade in proliferating dedifferentiated SMCs can induce growth inhibition and redifferentiation of SMCs with accelerated reendothelialization.

Adenoviridae↗

Expression of SR-PSOX, a novel cell-surface scavenger receptor for phosphatidylserine and oxidized LDL in human atherosclerotic lesions.

Receptor-mediated endocytosis of oxidized low density lipoprotein (Ox-LDL) by macrophages and the subsequent foam cell transformation in the arterial intima are key events in early atherogenesis. Recently, we have identified a novel macrophage cell-surface receptor for Ox-LDL by expression cloning from a cDNA library of phorbol 12-myristate 13-acetate-stimulated THP-1 cells, designated as the scavenger receptor for phosphatidylserine and oxidized lipoprotein (SR-PSOX). Here, we examined SR-PSOX expression in human atherosclerotic lesions. Total cellular RNA and fresh frozen sections were prepared from human carotid endarterectomy specimens (from 21 patients) and directional coronary atherectomy specimens (from 11 patients). Fragments of human aortas of 2 patients without visible atherosclerotic lesions served as negative controls. Quantitative reverse transcription-polymerase chain reaction demonstrated that SR-PSOX mRNA expression was prominent in atherosclerotic lesions but undetectable in normal aortas. Immunohistochemistry showed that SR-PSOX was predominantly expressed by lipid-laden macrophages in the intima of atherosclerotic plaques in carotid endarterectomy and directional coronary atherectomy specimens, although its expression was not detectable in normal arterial wall. Double-labeled immunohistochemistry confirmed that SR-PSOX is expressed by intimal macrophages. Taken together, SR-PSOX may be involved in Ox-LDL uptake and subsequent foam cell transformation in macrophages in vivo and thus may play important roles in human atherosclerotic lesion formation.

Animals↗

Delayed aortic rupture caused by an implanted anterior spinal device. Case report.

The authors describe a case of delayed aortic rupture following the application of a smooth-rod Kaneda (SRK) instrument. This is a rare but critical complication of anterior spinal fusion in which instrumentation is placed, and the authors wish to draw attention to the possible complications arising from such surgery. A few cases of this complication were reported in 1986. No reports have been published since then; perhaps because techniques and implant design have improved. In this case, a 53-year-old man suffered a T-11 fracture and related paraparesis, and he underwent decompression and anterior fusion in which an iliac bone graft was placed using an SRK device. Although his neurological deficit resolved postoperatively, nonunion of the grafted bone caused progressive kyphosis of the thoracolumbar spine. Twenty months after surgery, he complained of progressive gastrointestinal symptoms, and a delayed aortic rupture with a pseudoaneurysm was found surrounding the implant. The aortic pseudoaneurysm was replaced with an artificial vessel, and the SRK device was removed immediately. Delayed aortic rupture associated with anterior instrumentation is extremely rare but can occur. Even if the design of the implants can be improved, the placement of implants near the aorta and subsequent changes in the close anatomical relationship between the aorta and the implant eventually may result in this life-threatening complication. Careful follow-up examination and early removal of the implant, if necessary, are important.

Aneurysm, False↗

Relationship between papillary muscle size and benefit to cardiac function in mitral valve replacement with chordal preservation.

BACKGROUND AND AIM OF THE STUDY: Mitral valve replacement (MVR) with chordal preservation in patients with chronic mitral regurgitation (MR) has been reported to maintain systolic function of the left ventricle. However, the benefits of MVR with chordal preservation are not always predictable. The study aim was to ascertain the influence that papillary muscle (PM) size has on cardiac function after MVR with chordal preservation. METHODS: Postoperative regional shortening and its relationship with PM size were investigated by two-dimensional echocardiography in 18 patients who underwent MVR with chordal preservation, and nine patients without chordal preservation between 1986 and 1998 at Tenri Hospital. The PM cross-sectional area was measured in each patient, as well as postoperative fractional shortening (FS) of the septolateral, anteroposterior and vertical dimensions of the left ventricle. The technique of preserving all chordae tendineae involved reattaching the anterior leaflet chordae to the mitral annulus near each commissure. RESULTS: Postoperative FS of the septolateral and anteroposterior dimensions was better in patients with chordal preservation than in those without. In the former subgroup, a larger PM was associated with better FS of the left ventricle in the septolateral dimension (anterior PM, p <0.001, r = 0.78; posterior PM, p = 0.0010, r = 0.69), but not in the anteroposterior or vertical dimensions. This discrepancy in the relationship between PM size and functional benefits among the three dimensions may be related to the direction in which the PMs are suspended in our technique, or its effect on regional left ventricular function. CONCLUSION: The present study indicated that PM size may be used as a factor to better predict the outcome of MVR with chordal preservation.

Adult↗

[Renal autotransplantation in a patient with acute renal infarction following surgery for a dissecting aneurysm].

A 58-year-old woman experienced a sudden onset of severe chest and back pain and thus visited our center in October 1999. Contrast-enhanced computed tomography (CT) revealed a Stanford type A acute aortic dissection. The CT also demonstrated a 50 mm ascending aorta and dissection from the ascending aorta via the abdominal aorta to the level of the left renal artery. The perioperative transesophageal echocardiogram showed an intimal tear in the ascending aorta without valvular abnormality. Therefore, we performed graft replacement of the ascending aorta. On the first postoperative day, she developed oliguria and showed a sudden rise in serum creatinine (Cr) and blood urea nitrogen (BUN) levels, necessitating hemodialysis. She required daily hemodialysis or hemofiltration for twenty days. Thereafter, renal function recovered and dialysis was no longer performed. However, on postoperative day 26, the patient complained of sudden lumber pain. Unheralded oliguria was associated with worsening renal function. A CT scan at this point revealed infarction of the left kidney. During surgery, the left kidney was excised for heterotopic autotransplantation. Extensive thrombosis within a true lumen of the left renal artery was revealed. Following removal of the thrombus and perfusion with heparinized cold saline, renal autotransplantation to a heterotopic site in the pelvis were performed. Although the patient required hemodialysis for five days, renal function recovered gradually. She was discharged five months later. In our experience, it appears that heterotopic renal autotransplantation by which normal arterial perfusion distal to the dissection is reestablished is a good therapeutic option for reperfusion of the ischemic kidney compromised by a progressive dissection of the thoracoabdominal aorta.

Aortic Dissection↗

[Combined surgery for valvular and ischemic heart disease].

Combined coronary artery bypass (CAB) and valve surgery is one of the most challenging surgical procedures, but the operative results have improved over the years. We discuss several important points in combined surgery. The first point is cardioplegia, which should be perfect in such complex operations. Sufficient antegrade cold blood cardioplegia should be used in combined CAB and mitral valve surgery. Continuous retrograde cardioplegia is required in CAB and aortic valve surgery. The second point is the prosthesis and grafts. A mechanical prosthesis and arterial grafts should be used in younger patients, while a bioprosthesis and vein grafts with a left internal thoracic artery graft should be used in older ones. Finally, the choice of valve repair or replacement must be considered in mitral surgery with CAB. Valve repair is the choice in patients with mitral prolapse due to chordal rupture, because a perfect repair can be achieved using a well-known procedure. In cases in which repair appears difficult, replacement must be carried out as soon as possible. In mitral valve replacement the continuity between the papillary muscles and the mitral ring must be preserved for good left ventricular performance.

Aortic Valve↗

Haptic reproduction and interactive visualization of a beating heart based on cardiac morphology.

A goal of this work is proposal and construction of simulation methods of haptic reproduction and interactive visualization of a beating heart in cardiovascular surgical training and education. The data for the beating heart model was obtained from ECG-gated 3D MRI of a normal volunteer. The elastic information was assumed as a uniform value with clinically experienced elasticity. Using a real-time 3D graphics and a haptic device, a simulation environment of the beating heart was designed and implemented. After the construction, some cardiovascular surgeons evaluated the implemented system. Its visualization and haptic expression were scored excellent, but some details in haptic interface were remained to be improved. Finally, for more realistic cardiovascular surgical simulation, future development of the method is discussed.

Anatomy, Cross-Sectional↗

[Two successful cases of coronary artery bypass grafting followed by transluminal carotid angioplasty with stenting].

In coronary artery bypass grafting (CABG), carotid artery disease is an important factor that affects the incidence of perioperative stroke. The incidence of stroke following cardiac surgery is about 5 times higher in patients with carotid lesions than in patients without them. However, therapeutic strategies for those cases have not established in recent years. We report 2 successful cases of CABG following transluminal carotid angioplasty with stenting (TCAS) for concomitant coronary and carotid artery disease. The first case was a 71-year-old male who had left main trunk (LMT) and three-vessel coronary artery disease (CAD) and a 90% stenosis of the right internal carotid artery (ICA). One month after TCAS, triple CABG with cardiopulmonary bypass (CPB) was performed. The second case was a 75-year-old male who had LMT and single vessel CAD and a 99.9% stenosis of the lt. ICA. Considering his poor general conditions, combined strategy of off-pump CABG and PTCA was performed following TCAS. During and after cardiac surgery, they had no cerebral complications. Postoperative myocardial scintigraphy showed improved imaging in both cases. Preoperative TCAS is a safe and minimally invasive procedure for the patients with carotid artery stenosis who need CABG.

Aged↗

Treatment of acute stanford type B aortic dissection with a novel cylindrical balloon catheter in dogs.

BACKGROUND: Despite recent progress in medical and surgical treatment, acute type B aortic dissection still carries a high mortality rate. We have developed a novel cylindrical balloon catheter for less invasive treatment to block the entry of the dissection and induce thrombotic occlusion of the false lumen. The balloon has the shape of a sheet when deflated but a double-cylinder shape when inflated. Therefore, aortic blood flow is maintained through the cylindrical lumen during balloon inflation. METHODS AND RESULTS: Six beagle dogs underwent a left thoracotomy at the 6th intercostal space. An acute dissection of 4-cm length was created surgically on the descending aorta. The balloon catheter was inserted through the distal descending aorta and advanced to the entry site. The balloon catheter was inflated for 6 hours. The blood flow in the descending aorta and the position of the balloon was monitored by color Doppler echovasculography. Four dogs were killed humanely on the following day and 2 dogs 10 days after the surgery. The descending aorta was examined macroscopically and microscopically in all dogs. In all dogs, the false lumen was occluded by thrombi. Although no dog had clinical evidence of distal thromboembolism, 2 of the 4 dogs that were killed on the second postoperative day had fresh mural thrombi in the true lumen. CONCLUSIONS: The false lumen of the acute type B aortic dissection was effectively occluded by the novel cylindrical balloon catheter in the canine experimental model. The thrombus formation in the true lumen is the problem to be solved.

Acute Disease↗

Novel method to enhance sternal healing after harvesting bilateral internal thoracic arteries with use of basic fibroblast growth factor.

BACKGROUND: Poor healing of the sternum often limits the use of bilateral internal thoracic arteries (BITAs) in coronary bypass surgery, especially for diabetic patients. We have reported that basic fibroblast growth factor (bFGF) enhanced regeneration of the skull. This study was designed to evaluate the effects of topical use of bFGF on sternal healing after removing the BITAs. METHODS AND RESULTS: Forty-five Wistar rats were subjected to median sternotomy and were divided into 3 groups: 15 had the BITAs removed and had a bFGF sheet applied on the posterior table of the sternum (group A), 15 had just the BITAs removed (group B), and 15 had intact BITAs (group C). Five and 10 rats were euthanized 2 and 4 weeks after surgery, respectively, in all 3 groups. Peristernal blood flow, measured with use of a noncontact laser flowmeter, decreased after removal of the BITAs (P:<0.001). Four weeks after the surgery, PBF markedly increased only in group A (9.7+/-1.2, 6.5+/-0.6, and 8.2+/-0.5 mL x min(-1) x 100 g(-1) for groups A, B, and C, respectively; P:<0.01 by ANOVA). Four weeks after surgery, the following findings were obtained only in group A: (1) nearly completely healed sternum filled with regenerated bone tissue, (2) marked angiogenesis around the sternum, and (3) osteoblasts in an active form around the edge of the sternum. CONCLUSIONS: The results suggest that use of the bFGF sheet offset the sternal ischemia and accelerated sternal healing. This method may help to decrease sternal necrosis in high-risk patients or allow extended use of BITAs in coronary bypass surgery.

Administration, Topical↗

Inhibition of rho-associated kinase results in suppression of neointimal formation of balloon-injured arteries.

BACKGROUND: Rho-associated kinase (ROCK), an effector of small GTPase Rho, regulates vascular tone via a calcium sensitization mechanism and plays a key role in the pathogenesis of hypertension. However, its role in vascular growth remains unclear. METHODS AND RESULTS: Y-27632, a specific ROCK inhibitor, and the overexpression of dominant-negative ROCK suppressed the mitogen-induced DNA synthesis of cultured vascular smooth muscle cells (VSMCs), which indicates the essential role of ROCK in the control of VSMC proliferation in vitro. Y-27632 also suppressed the chemotaxis of VSMCs. Male Wistar rats were systemically given Y-27632 (35 to 70 mg. kg(-1). day(-1)) through an intraperitoneal infusion. The neointimal formation of balloon-injured carotid arteries was significantly suppressed in Y-27632-treated rats (intima/media ratio, 0.22+/-0.02) compared with vehicle-treated rats (intima/media ratio, 0.92+/-0.21) or hydralazine-treated rats with a similar blood pressure decrease (intima/media ratio, 1.03+/-0.15). The phosphorylation of myosin phosphatase and myosin light chain was elevated in injured arteries in a Y-27632-sensitive manner, indicating the augmentation of ROCK activity in neointimal formation. The downregulation of the cyclin-dependent kinase inhibitor p27(kip1) in injured vessels was reversed by Y-27632 treatment, reflecting the antiproliferative effect of ROCK inhibition in vivo. CONCLUSIONS: We conclude that ROCK plays a key role in the process of neointimal formation after balloon injury. Thus, the inhibition of ROCK may be a potential therapeutic strategy for treating vascular proliferative disorders and hypertension.

Amides↗

Stoichiometry of Na+-Ca2+ exchange in inside-out patches excised from guinea-pig ventricular myocytes.

1. The stoichiometry (nx) of cardiac Na+-Ca2+ exchange was examined by measuring the reversal potential of the Na+-Ca2+ exchange current (INa-Ca) in large inside-out patches, 'macro patches', excised from intact guinea-pig ventricular cells. 2. Cytoplasmic application of Na+ (Na+i) or Ca2+ (Ca2+i) induced INa-Ca which showed properties similar to INa-Ca in the giant membrane patch. The outward INa-Ca was depressed by an exchanger inhibitory peptide, XIP. 3. The reversal potential of the XIP-sensitive current indicated that nx was approximately 4 (3.6-4.2) at 9-40 mM Na+i, and nx tended to increase as Na+i was increased. Proteolysis by trypsin did not significantly affect the stoichiometry. Similar results were obtained from the reversal potential of INa-Ca that was induced by application of both Na+i and Ca2+i. 4. At 0.1 microM Ca2+i, nx was approximately 4 (3.7-4. 4) at 6-25 mM Na+i and tended to increase as Na+i was increased. When Ca2+i was changed from 0.1 to 1 and 1000 microM at constant 50 mM Na+i, the value was approximately 4 (3.6-4.4). 5. When the extracellular Na+ (Na+o) and Ca2+ (Ca2+o) concentrations were varied in the presence of 25 or 9 mM Na+i and 1 microM Ca2+i, nx was almost constant ( approximately 4) over the range 0.3-20 mM Ca2+o and 10-145 mM Na+o. 6. These results indicated that the stoichiometry of Na+-Ca2+ exchange is different from generally accepted 3Na+:1Ca2+, and suggested that the stoichiometry is either 4Na+:1Ca2+ or variable depending on Na+i and Ca2+i.

Animals↗

Aortoesophageal fistula caused by foreign body.

Aortoesophageal fistula is rare. A woman who developed aortoesophageal fistula after swallowing a fish bone developed hematemesis. 7 days later, we resected a false aneurysm near the left subclavian artery and repaired this section twice. Despite these measures, the woman died on hospital day 21. The clinical diagnosis was massive hematemesis from an infected aortic wall. The method of diagnosis, control of infection, and operative repair of aortoesophageal fistula are discussed.

Aortic Diseases↗