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Biomedical subjects

Satoshi Saito

Publications and source records attributed to Satoshi Saito.

At least 73 records · Page 4Linked to original sources

A case of transient bioprosthetic valve regurgitation and hemolysis devoloping early after surgery using Carpentier-Edwards valve.

The Carpentier-Edwards pericardial bioprosthesis has been markedly improved in the long-term results and valve-related complications including valve dysfunction, compared to the previous generation bioprosthesis. We report a patient in whom transient prosthetic valve regurgitation and hemolysis occurred early after mitral valve replacement using a Carpentier-Edwards pericardial bioprosthesis and were resolved by preservative therapy. The patient was a 77-year-old female diagnosed with severe mitral valve stenosis and insufficiency. She underwent mitral valve replacement with a Carpentier-Edwards pericardial bioprosthesis. Opening and closing of the three leaflets looked good on intraoperative transesophageal echocardiography (TEE). The only prosthetic valve regurgitation was evident at the central region where the leaflets form coaptation, and no abnormal findings were seen. Serum lactate dehydrogenase (LDH) was decreased to 405 U/l after surgery. However, LDH again began to increase on the 3rd day after surgery and it increased to 1,830 U/l on the 14th day after surgery. Hemolytic urine was detected on 10th day after surgery. PVL was not detected, but moderate abnormal regurgitation from the outside of the stent pocket was detected on TEE. Revision of valve replacement was considered, but LDH thereafter to 393 U/l on 41st day after surgery. The TEE was repeated, and only a trace of central jet was detected without abnormal regurgitation, unlike the previous examination. The patient did not develop any complications thereafter and was discharged on 47th day after surgery. LDH was nearly normal at the time of discharge.

Aged↗

Effect of a high-salt diet on gamma-aminobutyric acid-mediated responses in the nucleus tractus solitarius of Sprague-Dawley rats.

Previous study using an indirect gamma-aminobutyric acid (GABA) agonist indicated that high salt intake enhances sensitivity of nucleus tractus solitarius (NTS) projecting inhibitory input to rostral ventrolateral medulla sympathoexcitatory neurons. We further investigated the relationship between salt intake and the GABA system in NTS. Sprague-Dawley (S-D) rats consuming high dietary salt (8%) or low dietary salt (0.3%) for 3 weeks were used. Under chloralose-anesthesia, baseline arterial pressure (AP) and heart rate (HR) were similar in both groups. Bilateral injection into NTS of nipecotic acid, GABA(A) receptor agonist (muscimol), or GABA(B) receptor agonist (baclofen) elicited greater pressor responses in high-salt group. GABA(A) receptor antagonist, bicuculline and GABA(B) receptor antagonist, CGP-35348 elicited greater depressor responses. Phenylephrine or nitroprusside (i.v.) elicited similar respective increases or decreases in AP in both groups. Baroreflex sensitivity was similar. Thus, high-salt intake enhances both GABA(A) receptor- and GABA(B) receptor-mediated responses within NTS, thereby inhibiting elevation of AP.

Animals↗

Adenovirus-encoded hammerhead ribozyme to PDGF A-chain mRNA inhibits neointima formation after arterial injury.

To develop a strategy for gene therapy of restenosis following coronary angioplasty, we examined the effects of a recombinant adenovirus vector encoding a hammerhead ribozyme specific for rat platelet-derived growth factor (PDGF) A-chain mRNA (Ad. Ribozyme) and a control recombinant adenovirus vector encoding the Escherichia coli LacZ gene (Ad.LacZ) on neointima formation in rat carotid artery after balloon injury. Ad. Ribozyme (10(8) PFU/ml) markedly reduced the increased expression of PDGF A-chain mRNA and protein. Ad. Ribozyme significantly decreased the intima/media ratio (68%) of the injured artery, whereas Ad.LacZ had no effect on the intima/media ratio. Most carotid arteries developed thrombi by 14 days after balloon injury, whereas Ad. Ribozyme completely inhibited thrombus formation. Expression of thromboxane A2 (TXA2) receptor mRNA was significantly increased after balloon injury. Ad. Ribozyme significantly decreased the levels of TXA2 receptor. Expression of prostaglandin I2 (PGI2) synthase mRNA was significantly decreased after balloon injury. Ad. Ribozyme significantly increased levels of PGI2 synthase mRNA after balloon injury. The observation that adenovirus-encoded ribozyme to PDGF A-chain inhibits neointima formation may serve as a novel strategy to prevent restenosis after coronary angioplasty. Inhibition of growth factors by genetic approaches may yield new insights into the mechanisms underlying responses to vascular injury and lead to new therapeutic applications.

Adenoviridae↗

Complement 3 is involved in the synthetic phenotype and exaggerated growth of vascular smooth muscle cells from spontaneously hypertensive rats.

Vascular smooth muscle cells (VSMCs) from spontaneously hypertensive rats (SHR) show the synthetic phenotype and exaggerated growth in comparison with VSMCs from normotensive Wistar-Kyoto (WKY) rats. We investigated genes associated with the synthetic phenotype and exaggerated growth of VSMCs from SHR by microarray. Expression of 1300 transcripts was evaluated by microarray with total mRNA extracted from mid-layer aortic smooth muscle of 3-week-old SHR/Izumo and WKY/Izumo rats. mRNAs encoding sodium-dependent neurotransmitter transporter, epidermal growth factor precursor, EEF2, leptin receptor long-isoform b, clathrin assembly protein short form, and preprocomplement 3 (pre-pro-C3) were expressed only in aortic smooth muscle from SHR by microarray and by reverse-transcription polymerase chain reaction analysis. Pre-pro-C3 mRNA was detected only in cultured VSMCs from SHR. Exogenous C3 changed VSMCs to the synthetic phenotype. Antisense oligodeoxynucleotides (ODN) to C3 reduced the higher level of DNA synthesis in VSMCs from SHR. Antisense ODN to C3 increased expression of SM22alpha mRNA and decreased expression of osteopontin and matrix Gla mRNAs. It also decreased expression of growth factor mRNAs in VSMCs from SHR. In conclusion, we have shown that C3, independent of other complement molecules, has direct effects on the phenotype of VSMCs and stimulates growth of these cells. C3 is produced only by VSMCs from SHR. Therefore, C3 may be the gene underlying the synthetic phenotype and exaggerated growth of VSMCs from SHR. C3 may be a new target for the treatment of hypertension.

Animals↗

Chimeric DNA-RNA hammerhead ribozyme targeting transforming growth factor-beta 1 mRNA inhibits neointima formation in rat carotid artery after balloon injury.

We designed and synthesized a chimeric DNA-RNA hammerhead ribozyme targeting transforming growth factor (TGF)-beta 1 mRNA and found that this ribozyme effectively and specifically inhibited growth of vascular smooth muscle cells. We examined the effects of the chimeric DNA-RNA hammerhead ribozyme targeting TGF-beta 1 mRNA on neointima formation and investigated the underlying mechanism to develop a possible gene therapy for coronary artery restenosis after percutaneous transluminal coronary angioplasty. Expression of mRNAs encoding TGF-beta 1, p27kip1, and connective tissue growth factor (CTGF) in carotid artery increased after balloon injury. Fluorescein-isothiocyanate (FITC)-labeled ribozyme was taken up into the midlayer smooth muscle of the injured carotid artery. Both 2 and 5 mg of ribozyme reduced neointima formation by 65% compared to that of controls. Ribozyme markedly decreased expression of TGF-beta 1 mRNA and protein in injured vessel. Mismatch ribozyme had no effect on expression of TGF-beta 1 mRNA protein in injured vessel. Ribozyme markedly decreased expression of fibronectin, p27kip1, and CTGF mRNAs in injured vessel, whereas a mismatch ribozyme had no effect on these mRNAs. These findings indicate that the chimeric DNA-RNA hammerhead ribozyme targeting TGF-beta 1 mRNA inhibits neointima formation in rat carotid artery after balloon injury with suppression of TGF-beta 1 and inhibition of extracellular matrix and CTGF. In conclusion, the hammerhead ribozyme against TGF-beta 1 may have promise as a therapy for coronary artery restenosis after percutaneous transluminal coronary angioplasty.

Animals↗

Variability in quantitative measurement of the same segment with two different intravascular ultrasound systems: in vivo and in vitro studies.

We evaluated two different intravascular ultrasound (IVUS) systems, Atlantis and Intrafocus, to verify their accuracy and reproducibility. In an in vivo study on 20 consecutive patients with coronary artery diseases, the minimum lumen diameter (MLD), vessel diameter, lumen area (LA), vessel area, plaque area, and area stenosis rate (% AS) were respectively measured. In an in vitro study, MLD and LA were measured in four metal tubes with different diameters. All of the measured values except for % AS by Atlantis were significantly larger than the values obtained with Intrafocus. Nonuniform rotational distortion (NURD) was estimated as 34% in Atlantis and 1% in Intrafocus. The measurements by Atlantis were larger than the true values while the measurements by Intrafocus were less than the true values in all four metal tubes. These findings suggest that we should clearly avoid the use of different IVUS systems in the same study.

Aged↗

Intravascular ultrasound evaluation of ruptured plaque in the left main coronary artery misinterpreted as an aneurysm by angiography.

We report a patient who demonstrated a left main coronary aneurysm by angiography. Intravascular ultrasound (IVUS) revealed that it was in fact an ulceration, which indicated ruptured plaque. This case provides evidence that IVUS can permit a more powerful definition of ruptured plaque than angiography. On IVUS, ulceration exhibits significantly different characteristics from aneurysm.

Coronary Aneurysm↗

Soluble and cell-associated forms of some yet to be identified factor in transfused blood which promotes solid tumor growth in mice.

PURPOSE: The mechanism underlying the immunomodulation caused by blood transfusion has yet to be elucidated. The aim of the present study was to determine whether the transfusion of a soluble or insoluble factor present in stored blood can induce immunomodulation, which would thereby promote solid tumor growth. METHODS: C57Bl/6J mice were subcutaneously inoculated with B16-CG melanoma cells, which secrete beta-human chorionic gonadotropin (beta-hCG). Following inoculation, each of three different products of allogeneic and syngeneic blood were transfused on days 0 and 1: fresh whole blood, stored whole blood, and supernatants from the stored blood. Tumor growth was then monitored by measuring urinary beta-hCG. All mice were killed on day 15, and the tumor weight and volume were measured. RESULTS: Transfusion of all allogeneic blood products enhanced tumor growth, as did the stored syngeneic whole blood. Neither fresh syngeneic blood nor the supernatant from stored syngeneic blood promoted tumor growth. Although the tumors were not visually detectable until day 10 after inoculation, by day 7 the levels of urinary beta-hCG were significantly higher in the mice that received allogeneic blood supernatant than in the mice that received saline. CONCLUSIONS: A soluble alloantigen enhances solid tumor growth, as does an insoluble factor present in stored syngeneic whole blood. The immunomodulation associated with this factor begins to enhance tumor growth within 7 days after transfusion.

Animals↗

Hemodynamics of chronic nonpulsatile flow: implications for LVAD development.

Both experimental and clinical evidence suggest that pulse pressure is not required from a blood pump. End-organ function is well maintained with nonpulsatile systems, though pulse pressure may accelerate recovery from cardiogenic shock. Form follows function, so the effects of reduced pulse pressure on the arterial wall are not surprising. The ability to alter aortic wall morphology by reducing pulse pressure may have important implications for the future treatment of arterial pathology. Both centrifugal and axial-flow pumps can be miniaturized and are silent. Their reliability and user-friendly status may soon allow implantation at an earlier stage of cardiac deterioration. Doubts about the feasibility of long-term pulseless circulation are disappearing.

Animals↗

Comparison of coronary sinus morphology in patients with and without atrioventricular nodal reentrant tachycardia by intracardiac echocardiography.

INTRODUCTION: Dual AV nodal physiology is the electrophysiologic substrate for AV nodal reentrant tachycardia (AVNRT), but the anatomic basis for this arrhythmia remains to be elucidated. Atrial flutter (AFL) has been shown to be more frequently inducible in patients with AVNRT. METHODS AND RESULTS: A 3.2-French, 20-MHz intracardiac ultrasound (ICUS) catheter was introduced into the coronary sinus (CS), and two-dimensional ICUS images were recorded during transducer pullback in 21 patients with AVNRT and 18 control patients. Three-dimensional reconstruction of the CS was created using the TomTec Imaging system. The area of the CS lumen at 15 mm within the CS ostium (os) was not significantly different in patients with and without AVNRT (54.4 +/- 34.7 mm2 vs 39.1 +/- 28.5 mm2). However, the area of the CS os was significantly larger in patients with AVNRT than in those without (112.1 +/- 60.9 mm2 vs 71.7 +/- 44.4 mm2, P < 0.05). Three-dimensional morphology of the CS os revealed flaring in patients with AVNRT, giving it a "windsock" appearance. Sustained AFL was induced in 10 of 21 patients with AVNRT, but in none of 18 control patients (P < 0.005). CONCLUSION: The CS os was significantly wider in patients with AVNRT than in those without. These findings may have important implications for arrhythmia pathogenesis in AVNRT as well as AFL.

Adolescent↗

Relationship between anatomic location of the crista terminalis and double potentials recorded during atrial flutter: intracardiac echocardiographic analysis.

INTRODUCTION: The activation sequence in typical atrial flutter (AFL) around the tricuspid annulus is well described. However, activation of the remainder of the right atrium (RA) is not well defined. Previous studies have shown a linear block at the crista terminalis (CT) during AFL. The aim of this study was to evaluate the relationship between the location of the CT and the line of block by intracardiac echocardiography (ICE). METHODS AND RESULTS: Twenty-one patients with typical AFL were included in the study. The ICE imaging catheter (9-French with 9-MHz ultrasound transducer) was advanced to the RA. Under ICE guidance, a 20-pole roving catheter was used to map double potentials (DPs) during AFL, and three-dimensional images of the RA were reconstructed. During counterclockwise (CCW), clockwise (CW) AFL, or both, a line of conduction block manifested by DPs was identified at a septal site adjacent to the CT in 12 patients and in the posteroseptal RA in 9 patients. CONCLUSION: The functional line of block in CCW and CW AFL is localized not at the CT but at the septal edge of the CT or in the posteroseptal RA.

Action Potentials↗

Antithrombin III diminishes production of oxygen radical in endotoxin-infused rat lung.

The interaction of antithrombin III (AT) with cell surface glycosaminoglycans is known to have an inhibitory effect on inflammatory processes. We evaluated the effect of AT on endotoxin-induced production of oxygen radical in the pulmonary circulation using a fluorescent imaging technique. Also measured was the myeloperoxidase content of the lung, which served as an index of neutrophil accumulation, and neutrophil F-actin levels. Four groups of rats were infused for 2 h with endotoxin at 4.5 mg/kg/h (Et group), physiological saline (CT group), 100 U/kg of AT + endotoxin (AT group), or 100 U/kg of low-heparin-affinity latent-AT + endotoxin (L-AT group), respectively. Production of oxygen radical, neutrophil accumulation, and neutrophil F-actin levels were all significantly higher in the ET and L-AT groups than in the CT or AT group. Moreover; the levels of myeloperoxidase within the lung were well correlated with levels of oxygen radical production, which was consistent with the electron microscopic finding that cerium was deposited almost exclusively around neutrophils. Thus, it appears that AT most likely reduces F-actin formation in neutrophil by binding to glycosaminoglycans (e.g., syndecan-4) on the neutrophil, thereby reducing neutrophil accumulation in the lung, which would in turn inhibit oxygen radical production in the lung.

Actins↗

Hydrogen peroxide derived from intestine through the mesenteric lymph induces lung edema after surgical stress.

Compelling evidence indicates that the small intestine is the primary source of factors inducing lung injury after major surgery and that the lymphatic system is the major route by which these gut-derived factors reach the pulmonary circulation. This study investigated the mechanism of lung edema induced by surgical stress. After subjecting male, fasted, pathogen-free Sprague-Dawley rats to surgical stress (laparotomy and intestinal handling for 5 min), followed by ventilation for 5 h, we measured H2O2 production in the mucosa of small intestine and in the lung using 2',7'-dichlorofluorescein and intravital fluorescence microscopy. In addition, H2O2 in mesenteric lymph was measured using a quantitative assay; lung permeability was assessed as a function of extravasation of Evans blue dye; neutrophil accumulation was visualized by intravital fluorescence microscopy and assessed as a function of myeloperoxidase activity; and TNF-alpha levels were measured using a specific ELISA. The intensity of 2',7'-dichlorofluorescein fluorescence in the mucosa of small intestine, H2O2 levels of mesenteric lymph, and lung permeability were all significantly higher in rats subjected to surgical stress than in control animals. Moreover, all of these effects were blocked by pretreatment with a specific xanthine oxidase inhibitor. Surgical stress did not increase neutrophil accumulation or TNF-alpha production in the lung. In conclusion, surgical stress induces xanthine oxidase-dependent H2O2 production in the small intestine. The H2O2 then enters the mesenteric lymph and travels to the lung, where it increases capillary permeability and thus induces edema.

Animals↗

Methylprednisolone-induced expression of mitochondrial heat shock protein 60 protects mitochondrial membrane potential in the hypoxic rat liver.

This study investigated the contribution made by mitochondrial heat shock protein (hsp) 60 to methylprednisolone-mediated protection against mitochondrial membrane depolarization under hypoxic conditions. A low-flow hypoxia model was generated in isolated male, fasted, pathogen-free Sprague-Dawley rat livers by reducing perfusate inflow pressure from 10 to 2.5 cm H2O for 2 h. The effects of methylprednisolone on mitochondrial membrane potential and expression of mitochondrial hsp 60 protein and mRNA were determined. We measured mitochondrial membrane potential by imaging rhodamine 123 fluorescence. Induction of mitochondrial hsp 60 was detected using two different anti-hsp 60 antibodies: one against the N-terminal signal sequence, which reacted exclusively with cytoplasmic hsp 60, and one against a different epitope, which reacted with cytoplasmic and mitochondrial hsp 60. In addition, the distribution of hsp 60 mRNA was examined using in situ hybridization. We found that under hypoxic conditions, there was a significant decline in mitochondrial membrane potential that was accompanied by a mild decline in the level of mitochondrial hsp 60, and that cytosolic hsp 60 was translocated into mitochondria. Pretreatment with methylprednisolone inhibited the declines in mitochondrial membrane potential and hsp 60 protein, as well as the translocation of cytosolic hsp 60. This raises the possibility that one way in which methylprednisolone protects the mitochondrial membrane potential under hypoxic conditions is to induce expression of mitochondrial hsp 60.

Animals↗

The salvage of graft occlusion in a maintenace hemodialysis patient with tuberous sclerosis by percutaneous transluminal angioplasty using intravascular ultrasound: case report.

End-stage renal failure due to tuberous sclerosis is rare and there is no previous report of a patient with tuberous sclerosis undergoing long-term hemodialysis for over 18 years. The patency rate for a dialysis prosthetic graft is low, however, our patient's graft survived over 16 years. For thrombotic occlusion of a graft, we performed percutaneous thrombectomy and balloon angioplasty and salvaged graft occlusion. Moreover, this case is the first report in which the interventional procedure (mechanical thrombectomy and balloon angioplasty) could be observed by intravascular ultrasound in addition to angiography.

Aged↗

Wolff-Parkinson-White syndrome concomitant with asymptomatic Brugada syndrome.

A 29-year-old man was referred for electrophysiological testing and radiofrequency ablation because of repeated episodes of palpitation over 2 years. A 12-lead electrocardiogram during sinus rhythm showed manifest Wolff-Parkinson-White syndrome and during palpitation showed narrow QRS tachycardia at a rate of 213 beats/min. Following successful radiofrequency ablation of the left anterolateral accessory pathway, sustained atrial fibrillation was induced by atrial extrastimulation. Cibenzoline (2 mg/kg body weight) was injected to terminate atrial fibrillation. ST-T segment elevation in the right precordial leads was observed following cibenzoline administration. Ventricular fibrillation was reproducibly induced by ventricular extrastimuli (S1: 600 ms, S2: 220 ms, S3: 210 ms).

Adult↗

Evaluation of coronary artery remodeling in patients with acute coronary syndrome and stable angina by multislice computed tomography.

BACKGROUND: Multislice computed tomography (MSCT) was used to evaluate coronary artery remodeling in patients with acute coronary syndrome (ACS) and stable angina (SA). METHODS AND RESULTS: MSCT was performed in 31 patients with ACS and 26 patients with SA and intravascular ultrasound (IVUS) was performed in 28 of these 57 patients. In both the MSCT and IVUS analyses, coronary artery remodeling was assessed by the remodeling index (RI): RI >1.10 was defined as positive coronary artery remodeling (PCAR) and RI <0.95 was defined as negative coronary artery remodeling (NCAR). The RI assessed by MSCT closely correlated with that of IVUS (r=0.86, n=28). The vessel area at the region of maximum luminal narrowing was also comparable between the MSCT and IVUS measurements (r=0.92). PCAR was present in 19 patients (61.3%) with ACS, but in none of the patients with SA (p<0.0001). However, NCAR was present in only 1 patient with ACS (3.2%), but was present in 18 patients (62.9%) with SA. The RI was significantly larger in patients with ACS (1.19+/-0.18) than in those with SA (0.89+/-0.10, p<0.0001). CONCLUSION: MSCT accurately assesses coronary artery remodeling.

Acute Disease↗