Toshiharu Fukayama

Characterization of silk sponge in the wet state using 13C solid state NMR for development of a porous silk vascular graft with small diameter

The 13C solid state NMR spectra of the sponge prepared from Bombyx mori silk fibroin with different 13C labeling sites, [3-13C]Ser, [3-13C]Tyr and [3-13C]Ala were observed in dry and wet states. Here the silk fibroin sponge was prepared using poly(ethylene) glycol diglycidyl ether (PGDE) as porogen. Two broad peaks assigned to β-sheet and random coil were observed for each 13C-labeled site in the dry state. Moreover, in the wet state, one additional sharp peak assigned to random coil with high mobility due to the presence of water was observed. When the silk fibroin aqueous solution and PGDE was mixed in the sponge preparation process, the slow structural change from random coil to β-sheet structure occurs together with decrease in the motion of the silk fibroin backbone chain. The silk fibroin graft with small diameter was prepared with a knitted silk fiber tube coated with this silk fibroin sponge. The high porosity and suture retention strength which are comparable to an ePTFE vascular graft were attained. The excellent results, high patency and high tissue ingrowth, were obtained with the porous silk fibroin graft with small diameter by a rat abdominal aorta implantation experiment.

Effect of fibroin sponge coating on in vivo performance of knitted silk small diameter vascular grafts

ABSTRACT Vascular grafts under 5 mm or less in diameter are not developed due to a problem caused by early thrombus formation, neointimal hyperplasia, etc. Bombyx mori silk fibroin (SF) which has biodegradability and tissue infiltration is focused as tube and coating material of vascular grafts. Coating is an important factor to maintain the strength of the anastomotic region of vascular grafts, and to prevent the blood leak from the vascular grafts after implantation. Therefore, in this research, we focused on the SF concentration of the coating solution, and tissue infiltration and remodeling were compared among each SF concentration. Silk poly (-ethylene) glycol diglycidyl ether (PGDE) coating with concentrations of 1.0%, 2.5%, 5.0%, and 7.5% SF were applied for the double-raschel knitted small-sized vessel with 1.5 mm diameter and 1cm in length. The grafts were implanted in the rat abdominal aorta and removed after 3 weeks or 3 months. Vascular grafts patency was monitored by ultrasound, and morphological evaluation was performed by histopathological examination. SF concentration had no significant effects on the patency rate. However, tissue infiltration was significantly higher in the sample of 2.5% SF in 3 weeks, and 1.0% and 2.5% SF in 3 months. Also, in comparison of length inside of the graft, stenosis were not found in 3 weeks, however, found with 5.0% and 7.5% in 3 months. From these results, it is clear that 2.5% SF coating is the most suitable concentration, based on the characteristics of less stenosis, early tissue infiltration, and less neointimal hyperplasia.

Effects of Single Drug and Combined Short-term Administration of Sildenafil, Pimobendan, and Nicorandil on Right Ventricular Function in Rats With Monocrotaline-induced Pulmonary Hypertension.

Abstract: This study was designed to assess the progression of pulmonary arterial hypertension (PAH) and the effectiveness of therapy using recently investigated echocardiographic parameters. PAH is characterized by the progressive elevation of pulmonary artery pressure and right ventricular hypertrophy and dysfunction, which ultimately results in right-sided heart failure and death. Echocardiography results and invasive measurements of right and left ventricular systolic pressures were compared after 3-week administrations of sildenafil (S group), pimobendan (P group), nicorandil (N group), and their combinations (SP and SPN groups) in male rats with monocrotaline (MCT)-induced pulmonary hypertension (M group) and without this condition (C group). The groups that received pimobendan alone and in combinations (SP and SPN groups) showed improvement in their echocardiographic parameters of systolic function. A significant improvement of diastolic function was achieved in the SPN group. Invasive measurements showed the most significant decreases of right ventricular systolic pressure in the N and SPN groups, and the use of pimobendan resulted in a comparatively low risk of adverse hemodynamic effects (left ventricular systolic pressure). Although our results suggested the attenuation of PAH severity in all treatment groups, PAH could not be reversed.

Echocardiographic Evaluation of Myocardial Changes Observed After Closure of Patent Ductus Arteriosus in Dogs

Background Closure of PDA can be associated with echocardiographic changes including deterioration of LV systolic function. Although PDA is commonly encountered in dogs, few comprehensive reports of echocardiographic changes in dogs with PDA closure are available. Objectives To evaluate the short‐term echocardiographic changes observed after PDA closure in dogs using strain analysis. Animals Seventeen client‐owned dogs with left‐to‐right PDA. Methods Echocardiographic evaluations, including standard echocardiography and two‐dimensional tissue tracking (2DTT), were performed before and within 3 days of PDA closure. Results Preclosure examination showed LV and left atrial dilatation indicating volume overload as a result of PDA. Closure of PDA resulted in significant reduction of LVIDd (<.0001) and LA/Ao (0.01) without change in LVIDs, suggestive of decreased preload. Postclosure LV systolic dysfunction was observed with significant decreased in FS (<.0001) and strain values (P = .0039 for radial strains, P = .0005 for circumferential strains). Additionally, significant LV dyssynchrony (P = .0162) was observed after closure of PDA. Conclusions and Clinical Importance Closure of PDA resulted in decreased preload as a result of alleviation of LV volume overload, which in turn caused transient deterioration of LV systolic function. Additionally, this study demonstrated that strain analysis is load dependent. Therefore, care should be taken when interpreting strain measurements as an indicator of LV systolic function.

Effective new membrane for preventing postthoracotomy pleural adhesion by surface water induction technology

Background After thoracic surgery, adhesions between the pleura can cause substantial complications. This study investigated the effectiveness of a novel membrane utilizing surface water induction technology to prevent adhesions. Methods Eight beagles were divided into an experimental group (five males) and a control group (three females). The experimental group underwent thoracotomy on both the left and right sides of the chest. Both sides received the membrane, and the membrane on one side was glued to the pleura using tissue adhesive. The control group underwent thoracotomy only on the left side. Two weeks postoperatively, all dogs were sacrificed and adhesions were evaluated macroscopically and microscopically. Results Severe adhesion was seen between the parietal and visceral pleura in all control dogs, whereas the experimental group showed minor adhesion in only one dog on one side. Conclusions Our novel anti-adhesive membrane appeared highly effective in preventing postthoracotomy pleural adhesions.

Development of an Anti-Adhesive Membrane for Use in Video-Assisted Thoracic Surgery

Background: The need to prevent postoperative adhesions after surgery has been considered a significant challenge in thoracic surgery, especially with the advent of video-assisted thoracic surgery (VATS). While preventive materials for postoperative adhesions have been studied for many years, they are all still in the development phases. Methods: In this animal study, an insoluble hyaluronic acid membrane was used in VATS for wedge resection to test its operability and to examine the bodys response to the membrane. Ten beagles were divided into two groups, an experimental group and a negative control group. In the experimental group, an insoluble hyaluronic acid membrane containing glycerol was used as the test membrane (10 x 10 x 0.1 cm3). The test membrane was implanted in the left thoracic cavity of the animal under VATS following wedge resection. The animals were observed for two weeks and then euthanized for examination. Results: Macroscopically, the median adhesion score was lower in the experimental group (0) than in the control group (2.5). On histopathological examination, the test membrane elicited only a minor inflammatory response and foreign body reaction. Conclusion: The test membrane showed satisfactory operability and appears to be a practical material to prevent postoperative adhesions after thoracic surgery in VATS.

Effects of a Sustained-Release Form of Isosorbide Dinitrate on Left Atrial Pressure in Dogs with Experimentally Induced Mitral Valve Regurgitation

BACKGROUND The effects of isosorbide dinitrate (ISDN) have not been sufficiently investigated in conscious dogs with mitral valve regurgitation (MR). OBJECTIVE The objective was to investigate the effects of a sustained-release form of ISDN (sr-ISDN) on hemodynamics and the autonomic nervous system in dogs with MR. ANIMALS Six healthy Beagles weighing 11.2 ± 2.2 kg (2 years of age; 2 males and 4 females) were used. METHODS Experimental, crossover, and interventional study. Dogs with experimentally induced MR were administered placebo, 2, 5, and 10 mg/kg sr-ISDN PO on separate days with a 7-day washout period between randomized dosings. Left atrial pressure (LAP) had been recorded continuously from 30 minutes before administration of sr-ISDN to 12 hours after administration. RESULTS LAP was significantly decreased after administration in the 5 and 10 mg/kg groups. Significant decrease was observed at 3 and 4 hours after administration in the 5 mg/kg group. In the 10 mg/kg group, significant decrease was observed at 2, 3, 4, 5, 6, 7, 10, and 11 hours after administration. The lowest value was observed at 4 hours after administration in the 5 and 10 mg/kg groups (20.9 ± 4.2 to 15.9 ± 3.9 mmHg, P < .01, and 21.3 ± 4.0 to 13.6 ± 4.2 mmHg, P < .001). CONCLUSIONS AND CLINICAL IMPORTANCE Sustained-release form of ISDN showed significant decrease of LAP in the 5 mg/kg and 10 mg/kg groups, and duration of effect was dose related.

Utility of Lung Ultrasonography for Detection of Pleural Adhesions in Dogs

To assess lung respiratory movement (“lung sliding”) in dogs using B‐mode ultrasonography (US) and to develop a method that assesses adhesions between the parietal pleura and the lung.

Hybrid technique coil embolisation for intrahepatic arterioportal fistula in a cat: case report

Case summary A 13-month-old, female, mixed breed, 4.0 kg cat was referred with a 6 month history of decreased appetite, loss of vigour and intermittent vomiting. Physical examination revealed no cyanosis or wasting, and no audible heart murmur was auscultated. Blood profile revealed mild anaemia and mildly elevated postprandial serum ammonia (109 µg/dl). Abdominal ultrasonography revealed dilation of an intrahepatic portal vein branch and an intrahepatic aneurysm, with splenomegaly and ascites. Hepatic arteriovenous fistula/hepatic artery–portal vein fistula with multiple acquired portosystemic shunts was strongly suspected. Medical control was achieved using antibiotics, liver-protecting agents, a low-protein diet and blood transfusions. However, because medical treatment proved ineffective, coil embolisation was performed on day 11, using a hybrid approach via the mesenteric vein. Subsequent follow-up showed good appetite, with no signs of diarrhoea or ascites. Abdominal ultrasonography revealed that the mosaic pattern around the site of coil placement in the portal vein branch had improved and pulsatility had disappeared. Relevance and novel information Intrahepatic arterioportal fistula involves a circulatory shunt between the hepatic artery and the hepatic or portal vein within the liver, and may be congenital or acquired. Both forms have been reported in humans, but most cases in cats have been congenital. Few reports have described treatment methods or prognosis in cats. We report here that coil embolisation using a hybrid approach is a procedure offering easy, effective treatment by blocking hepatofugal blood flow.

Comparative effect of carperitide and furosemide on left atrial pressure in dogs with experimentally induced mitral valve regurgitation.

BACKGROUND The effects of carperitide on left atrial pressure (LAP) in dogs with mitral valve disease (mitral regurgitation, MR) have not been documented. OBJECTIVE The objective was to compare the short-term effects of carperitide versus furosemide on LAP and neurohumoral factors in MR dogs. ANIMALS Six healthy Beagle dogs weighing 9.8-12.6 kg (2 males and 4 females; aged 3 years) were used. METHODS Experimental, randomized, cross-over, and interventional study. Carperitide 0.1 μg/kg/min or furosemide 0.17 mg/kg/h (1 mg/kg/6 h) was administered to dogs with surgically induced MR for 6 hours, and after a 14 day wash-out period, the other drug was administered. LAP, plasma renin activity, plasma aldosterone, and echocardiographic variables were measured. RESULTS Left atrial pressure was decreased similarly after the administration of carperitide 0.1 μg/kg/min and furosemide 0.17 mg/kg/h (1 mg/kg/6 h) compared with baseline in dogs with MR (Baseline 14.75 ± 3.74 mmHg, carperitide 10.24 ± 4.97 mmHg, P < .01, furosemide 10.77 ± 5.06 mmHg, P < .05). Plasma renin activity and plasma aldosterone were significantly lower after the administration of carperitide than after the administration of furosemide (P < .05, respectively). CONCLUSIONS AND CLINICAL IMPORTANCE Carperitide significantly decreased LAP in dogs with acute MR caused by experimental chordal rupture. Carperitide can have additional benefits from the viewpoint of minimal activation of neurohumoral factors in the treatment of dogs with MR. Additional studies in dogs with spontaneous disease are warranted.