Assessment of the subcutaneous degradation process of insoluble hyaluronic acid in rats.

Insoluble hyaluronic acid (IHA) may prevent adhesions by forming a physical barrier during the period when postoperative adhesions form. This study was performed to verify the changes that a solid IHA membrane undergoes as it is degraded in vivo, and to ascertain the swelling rate of IHA required for it to function as a physical barrier during the postoperative adhesion formation period. Nine female WI rats weighing 300-400 g were used. Discs 8 mm in diameter were cut out of dry IHA membranes made of IHA with a swelling rate (wet weight/dry weight) of either 2.47 (high-swelling IHA) or 1.94 (low-swelling IHA). They were placed in saline to swell and then washed with saline before subcutaneous implantation in four pockets in each rat. The high-swelling IHA started to degrade more rapidly than the low-swelling IHA. There was no evidence of degradation of the low-swelling IHA until day 7, but once it had started, the speed of degradation tended to be similar to that of the high-swelling IHA. The present results showed that, when IHA is implanted subcutaneously in rats, it is degraded over time in a phased process. The swelling rate required for the use of IHA as a postoperative adhesion barrier was also suggested.

Development of a biointegrated mandibular reconstruction device consisting of bone compatible titanium fiber mesh scaffold.

Coating biomaterials with a thin hydroxyapatite (HA) was proven effective in enhancing bone compatibility. Segmental bone defects are considered as the most difficult defect to repair in bone regeneration therapy. We developed submicron-thin HA-coated titanium fiber mesh scaffolds to reconstruct immediately loaded segmental mandibular defects and evaluated their bone compatibility in vitro and in vivo. Human osteoblasts attachment, proliferation, and osteocalcin expression in non- and HA-coated scaffolds were evaluated. A 10-mm long segmental bone defect in a rabbit mandibular bone was reconstructed with non- or HA-coated scaffolds, which were removed at 9 and 21 weeks, to evaluate the mechanical strength of the bone-scaffold connection and the bone formation around the scaffold. Expression of osteocalcin was greater in HA-coated scaffolds. In vivo bone formation in HA-coated scaffolds was greater than that in non-coated scaffolds at 21 weeks. Newly formed bone in HA-coated scaffolds mostly restored bone continuity. Scanning electron microscopy identified strong integration of the bone and HA-coated scaffolds. The mechanical strength of the bone-scaffold connection was 3-fold greater in HA-coated scaffolds than that in non-coated scaffolds. These results suggest that a thin HA-coated titanium fiber mesh scaffold is a bone-compatible mandibular reconstruction device in immediately loaded segmental defects.

Elevated microsatellite alterations at selected tetra-nucleotide (EMAST) in non-small cell lung cancers--a potential determinant of susceptibility to multiple malignancies.

The present study evaluated the potential clinicopathologic significance of elevated microsatellite alteration at selected tetra-nucleotide (EMAST) in non-small cell lung cancer (NSCLC). Sixty-five NSCLCs (19 squamous cell carcinomas, 39 adenocarcinomas, one adenosquamous cell carcinoma, and 6 large cell carcinomas) were examined for EMAST in the ten selected tetra-nucleotide markers. Traditional microsatellite instability (MSI) in the five mono- or di-nucleotide markers of the Bethesda panel was also examined, and compared with EMAST. The incidence of EMAST was higher than that of traditional MSI, as 64.6% (42/65) and 12.3% (8/65) tumors respectively exhibited EMAST and traditional MSI in at least one marker. EMAST and traditional MSI appear to occur independently, as no significant association in their incidence was found (Fisher's exact test, P = 0.146). Subjects who exhibited EMAST in two or more markers had a significantly higher incidence of history of other malignant neoplasms (42.9% [9/21]), compared to those with less than two markers (16.3% [7/43] (Chi-square test, P = 0.021)). Taken together, impairment of molecular machinery for maintaining stable replication of the tetra-nucleotide-repeating regions, which would differ from machinery for mono- or di-nucleotide-repeating regions, may elevate susceptibility to NSCLCs and certain neoplastic diseases. Elucidation of the potential molecular mechanism of EMAST is expected to lead to a discovery of a novel genetic background determining susceptibility to NSCLC and other multiple neoplasms. This is the first report describing a clinicopathologic significance of EMAST in NSCLC.

Anti-adhesive membrane for pleural cavity.

An anti-adhesive membrane containing a large amount of glycerin was developed for lung surgery and was tested in the pleural cavity of six dogs. The test membranes were put between the lung and the chest wound of the pleural cavity wall to separate them. In five of the animals, no adhesion was observed after 3 weeks in the area where the membrane had been inserted, but the area without the membrane showed firm adhesion between the lung and the pleural cavity wall. A sixth animal observed for 3 months also showed no adhesion. Seprafilm, which is the product of choice for peritoneal surgeries, was used as a control in six dogs. Seprafilm could not prevent adhesion in the pleural cavity of all six animals after 3 weeks observation. The new test membrane contained glycerin, which gathered and dispersed abundant water. Together with this, growth factors are also dispersed, resulting in dilution of excessive growth factors at the wound sites. In general, fibroblasts do not migrate in an extremely hydrous gel matrix. Migration of fibroblasts into the membrane is minimized, resulting in the prevention of formation of adhesion tissue composed of fibroblasts and collagen fibers. From the results, we assume that water can prevent adhesion after surgery.

Vascular prosthesis rupture caused by contact with rib stump after thoracic aorta replacement.

A 42-year-old male with Marfan syndrome, who had undergone aortic root and total arch replacement for type-A acute aortic dissection at the age of 40, underwent descending aorta replacement with woven Dacron (Vascutek Ltd., Renfrewshire, Scotland) because of pseudoaneurysm at the site of the distal anastomosis and an enlarged pseudolumen of the dissecting descending aorta. The fourth and eighth ribs were cut at their anterior and posterior sites to allow wide exposure of the entire descending aorta. Postoperative computed tomographic scanning showed that the vascular prosthesis posteriorly contacted the eighth rib stump. On the postoperative day 25, the patient collapsed and developed severe hypotension. Emergency thoracotomy revealed a 6 mm in diameter hole on the posterior side of the vascular prosthesis. One day later, the patient died of cardiac dysfunction resulting from sustained hypotension. Electron microscopic examination of the vascular prosthesis showed that the hole was caused by frayed fabric and disrupted polyester fibers. Our experience warns that a woven polyester vascular prosthesis could rupture within 3 weeks of contacting a rib stump.

Method for inducing the growth of new arteries in the myocardium.

OBJECTIVE: The creation of new coronary arteries has long been an objective of cardiac research. I describe a method for creating new blood vessels in the myocardium of the left ventricular wall in animals. METHODS: The myocardium was pierced by a fistula. Then a biodegradable hydrogel fiber with antithrombogenic and nonadhesive properties was inserted into the fistula with a venous catheter. Nine dogs were used. Three fibers were inserted in each heart, and two additional punctures were made and left empty as controls. RESULTS: During absorption of the fiber, the luminal surface of the fistula became lined with endothelial cells and developed many openings to capillary blood vessels of the myocardium naturally. Three straight fibers were inserted so they intersected in the myocardium. They created a new branched vessel. The fistulas had connections to original coronary arteries and worked as new arteries to supply blood to the area where they were created. CONCLUSIONS: It was possible to create new blood vessels in the myocardium in animals.

An experimental study of apico-aortic valved conduit (AAVC) for surgical treatment of aortic stenosis in dogs.

A new valved conduit was developed using a canine aortic valve. The bioprosthetic valve was fixed with glutaraldehyde and epoxy compound (Denacol-EX313/810). A vascular graft composed of ultra-fine polyester fiber (10 mm in diameter, 200 mm in length) was used. Four dogs underwent apico-aortic valved conduit (AAVC) implantation and aortic banding (bypass group, BG), while another 4 dogs underwent aortic banding without AAVC implantation (control group, CG). Cardiac catheterization and angiocardiography were performed for assessment of hemodynamics 2 weeks and 6 months after surgery. Left ventricular systolic pressure, left ventricular end-diastolic pressure and the left ventricular-aortic pressure gradient differed significantly (P<0.01) between the BG and CG dogs. Left ventricular angiocardiography showed patency of the valved conduit in all the BG dogs. Echocardiography was performed before and 2, 4 and 6 months after surgery, and showed that while pressure overload caused concentric myocardial hypertrophy in the CG dogs, the left ventricle dilated eccentrically in the BG dogs. Furthermore, relief of left ventricular pressure overload by AAVC was maintained.

Comparison of extracapillary and endocapillary blood flow oxygenators for open heart surgery in dogs: efficiency of gas exchange and platelet conservation.

The goal of the current study was to compare the efficiency of gas exchange and platelet conservation of a new extracapillary blood flow oxygenator versus an endocapillary blood flow oxygenator during open heart surgery with extracorporeal circulation in dogs. Dilation and remodeling of the right ventricular outflow tract of dogs was performed using a patch graft technique to simulate pulmonary stenosis. Sequential pre- and post-operative blood analysis revealed that gas exchange efficiency and platelet conservation was significantly greater with the extracapillary blood flow oxygenator than with the endocapillary blood flow oxygenator. However, the priming volume of the extracapillary blood flow oxygenator was significantly greater, leading to hemodilution. We conclude that while the extracapillary blood flow oxygenator provided benefits in terms of gas exchange and platelet conservation, development of a smaller extracapillary blood flow type oxygenator to reduce hemodilution effects would be beneficial.

A long term comparison between Denacol EX-313-treated bovine jugular vein graft and ultrafine polyester fiber graft for reconstruction of tight ventricular outflow tract in dogs.

A Denacol EX-313 (Denacol)-treated bovine venous graft and an ultrafine polyester fiber (UFPF) graft were transplanted as patch graft into the right ventricular outflow tract under extracorporeal circulation in six dogs each experimentally. Hemodynamics in right heart and histological findings around the graft were compared between both groups over a period of one year after grafting. Pressure measurements and angiocardiography were performed through a cardiac catheter. Right ventricular pressure, pulmonary artery pessure, and right ventricle to pulmonary artery gradient were within normal limits in both groups at 1, 2, 3, 4, 6, and 12 months or more after grafting. No difference were seen between the values for the Denacol and the UFPF group. Histologically, the medial surface at the site of grafting was covered with vascular endothelial cells at one month after grafting in both groups. The density of the vascular endothelial cells increased with time after grafting, showing no clear difference between the two groups. Subendothelial layers comprised of collagen fibers, elastic fibers, and inflammatory cells decreased with time in both groups, but there was less cell infiltration in the Denacol group than in the UFPF group at all time points after grafting. In addition, the central cut thickness value of the graft tended to be thinner in the Denacol group than in the UFPF group at all observation time points after grafting. In the Denacol group, very slight metaplasia of cartilage was noted in a portion of the graft margin at six months or more after grafting, but no other abnormalities were observed. These results suggest that the Denacol-treated bovine venous graft has better grafting characteristics than the UFPF graft with easier intra-operative handlings and less tissue reactions after grafting.

Flow dynamics in internal thoracic artery grafts 10 years after coronary artery bypass grafting.

BACKGROUND: Flow dynamics in internal thoracic artery grafts 10 years after surgery are not known. METHODS: Doppler examination was performed in native internal thoracic arteries as a control (n = 8) and in internal thoracic artery grafts to the left anterior descending coronary artery 6 months postoperatively (group A, n = 25), at 5 years (group B, n = 14), and at 10 years (group C, n = 11). RESULTS: Each graft group showed a diastolic to systolic peak velocity ratio of less than 1.0 at the proximal end, and more than 1.0 at the distal end, but the control group showed a ratio of less than 1.0 throughout the length of the artery. The diastolic peak velocity of the graft groups was significantly faster than that of the control group at the distal end (versus group A, p < 0.01; versus group B, p < 0.005; and versus group C, p < 0.05). The systolic peak velocity of the graft groups was significantly lower than that of the control at the proximal end (versus group A, p < 0.0001; versus group B, p < 0.005; and versus group C, p < 0.0005). There were no significant differences of flow velocities among the graft groups and graft diameter among the four groups. CONCLUSIONS: Although the internal thoracic artery is systolic predominant, when native artery is used as graft, it changes its hemodynamics to diastolic predominance, especially at the distal end. Even after 10 years, graft flow dynamics are unchanged. This hemodynamic character may be one of the factors related to the superior long-term patency.