Small-diameter (less than 6 mm in diameter) vascular grafts are highly desirable due to the large demand for surgical revascularization; however, there are no available artificial grafts. Vascular grafts of 1.5 mm diameter prepared by our group with silk fibroin fiber have been proved to be excellent grafts with remarkably high patency and remodeling, based on rat implantation experiment (Enomoto et al., 2010). In this study, a silk fibroin vascular graft with 3 mm diameter which can be used for the coronary arteries or lower extremity arteries is prepared with a double-raschel knitted Bombyx mori silk fiber tube coated with B. mori silk fibroin sponge. Here the silk sponge is prepared from an aqueous solution of the silk fibroin and poly(ethylene) glycol diglycidyl ether as porogen. Sufficient strength, proper elasticity, and protection from loose ends in the implantation process are obtained for the silk fibroin graft; low water permeability and relatively large compliance are also attained. These excellent physical properties make silk fibroin grafts suitable to be implanted in a canine model.

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Background: The effects of pimobendan on left atrial pressure (LAP) in dogs with mitral valve disease (MR) have not been documented in a quantitative manner.Objective: The objective was to document and study the short-term effects of pimobendan on LAP and echocardiographic parameters in MR dogs.Animals: Eight healthy Beagle dogs weighing 10.0-14.7 kg (3 males and 5 females; aged 2 years) were used. Methods: Experimental, cross-over, and interventional study. Dogs with surgically induced MR received pimobendan at either 0.25 mg/kg or 0.50 mg/kg PO q12h for 7 days and then, after a 7-day wash-out period, the other dosage. LAP was measured for 30 minutes at baseline and again on days 1, 2, 4, and 7 of pimobendan administration.Results: Mean LAP was significantly decreased after the administration of 0.25 mg/kg (15.81 ± 5.44 mmHg to 12.67 ± 5.71 mmHg, P < .001) and 0.50 mg/kg (15.76 ± 5.45 mmHg to 10.77 ± 5.23 mmHg, P < .001). Also, the 0.50 mg/ kg group led to a significantly lower LAP (P < .01) compared with the 0.25 mg/kg group. Significant reduction was seen for the first time 4 days after the administration of 0.25 mg/kg and a day after the administration of 0.50 mg/kg.Conclusions and Clinical Importance: Pimobendan decreased LAP in a dose-dependent manner in dogs with acute MR caused by experimental chordal rupture. This study did not evaluate adverse effects of high-dose pimobendan, and additional studies in clinical patients are warranted.

In the field of surgical revascularization, the need for functional small-diameter (1.5-4.0 mm in diameter) vascular grafts is increasing. Several synthetic biomaterials have been tested for this purpose, but in many cases they cause thrombosis. In this study, we report the development of small-diameter vascular grafts made from silk fibroin fibers from the domestic silkworm Bombyx mori or recombinant silk fibroin fibers from a transgenic silkworm. The vascular grafts were prepared by braiding, flattening and winding the silk fibers twice onto a cylindrical polymer tube followed by coating with an aqueous silk fibroin solution. The grafts, which are 1.5 mm in inner diameter and 10 mm in length, were implanted into rat abdominal aorta. An excellent patency (ca. 85%, n= 27) at 12 months after grafting with wild-type silk fibers was obtained. Endothelial cells and smooth muscle cells migrated into the silk fibroin graft early after implantation, and became organized into an endothelium and a media-like smooth muscle layer.

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.

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Background: The effects of furosemide on left atrial pressure (LAP) in dogs with mitral regurgitation (MR) have not been documented in a quantitative manner and between different routes of administration.Objective: To document LAP and echocardiographic parameters in MR dogs administered furosemide IV or PO, in order to document changes in LAP after furosemide treatment.Animals: Five healthy Beagle dogs (3 males and 2 females; aged 2 years) were used. Methods: Experimental, cross-over, and interventional study. LAP was measured before the administration of furosemide, and 30 minutes, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, and 24 hours after administration. Furosemide 1, 2, or 4 mg/kg IV, PO or placebo was administered.Results: LAP was significantly decreased with all administrations of furosemide but not after placebo (P o .05, respectively). The max reduction was observed 1 hour (1 mg/kg IV, 15.04 AE 7.02 mmHg), 3 hours (2, 4 mg/kg IV, 13.28 AE 8.01, 9.23 AE 4.92 mmHg), 4 hours (1 mg/kg PO, 14.68 AE 11.51 mmHg), and 5 hours (2, 4 mg/kg PO, 13.19 AE 10.52, 10.70 AE 7.69 mmHg). E wave and E/Ea were significantly decreased corresponding to the reduction of LAP after administration of 2 and 4 mg/kg (P o .05, respectively).Conclusions and Clinical Importance: LAP was decreased in proportion to the dosage of furosemide, which did not significantly differ between IV and PO of the same dosages. E wave and E/Ea might be useful for the treatment evaluation of furosemide.Key words: Radio telemetry system; Total circulating blood volume; Transmitral blood flow.M itral valve disease is the most common cardiac disease in dogs. As many as three quarters of all dogs with signs of congestive heart failure suffer from mitral regurgitation (MR) caused by myxomatous degeneration of the valve leaflets or the chordae tendineae.1,2 MR increases the left atrial pressure (LAP) which potentially results in left atrial dilation. Elevated LAP causes pulmonary edema that can lead to cough, dyspnea, and even death.3 Therefore, LAP needs to be reduced to avoid these clinical signs.Furosemide, a loop diuretic, has a strong diuretic effect and is commonly used for the treatment of pulmonary edema in patients with MR. 4 Furosemide reduces the total circulating blood volume, which in turn reduces the LAP or the left ventricular filling pressure, and leads to the clinical improvement of the patients. [5][6][7][8][9] There are several administration routes for furosemide, including IV, PO, SC, and IM. Pharmacokinetics of furosemide has been compared between IV and PO administration. However, the effects of furosemide on LAP in dogs with MR have not been well documented in a quantitative manner because there are some difficulties in measuring LAP directly. We have previously reported the 24-hour LAP profiles of and the effect of angiotensin-converting enzyme (ACE) inhibitors on experimentally induced MR dogs with a radio telemetry system. 10,11 The previous study has demonstrated that this system is useful for the evaluation of hemodynamic changes that occur...

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