The localized expression of a number of extracellular matrix genes was evaluated over tinie in a novel rat rotator cuff injury model. The supraspinatus tendons of rats were severed at the bony insertion and repaired surgically. The healing response was evaluated at I , 2, 4, and 8 weeks post-injury using histologic and in situ hybridization techniques. Expression patterns of collagens (I, 11, 111, IX, X, XII), proteoglycans (decorin, aggrecan, versican, biglycan, fibromodulin), and other extracellular matrix proteins (elastin, osteocalcin, alkaline phosphatase) were evaluated at the healing tendon to bone insertion site. Histologic results indicate a poor healing response to the injury, with only partial recreation of the insertion site by 8 weeks. In situ hybridization results indicate a specific pattern of genes expressed in each zone of the insertion site (i.e., tendon, fibrocartilage, mineralized cartilage, bone). Overall, expression of collagen types I and XII, aggrecan, and biglycan was increased, while expression of collagen type X and decorin was decreased. Expression of collagen type I, collagen type XII, and biglycan decreased over time. but remained above normal at 8 weeks. Results indicate that the rat supraspinatus tendon is ineffective in recreating the original insertion site, even at 8 weeks post-injury, in the absence of biological or bioiiiechanical enhancements.

Chylothorax is a devastating disease, and the success rates from either medical or surgical management are less than satisfactory. In some animals with chylothorax, a thickening of the pericardium occurs that is associated with chronic irritation induced by chyle. We hypothesized that pericardial thickening would lead to increased right-sided venous pressures and that abnormal venous pressures would act to impede the drainage of chyle via lymphaticovenous communications after thoracic duct (TD) ligation. We also hypothesized that serosanguineous effusions that occurred after TD ligation could effectively be treated or prevented by pericardectomy in affected animals. TD ligation plus pericardectomy was performed in 17 animals, and pericardectomy alone was performed in an additional 3 animals that presented during a 5.5-year period to the Texas A&M University (College Station, TX). Nineteen animals presented for an evaluation of idiopathic chylothorax (9 dogs and 10 cats), and 1 dog presented for serosanguineous pleural fluid after TD ligation that had been performed elsewhere. Echocardiography was normal in all animals, except for a subjectively thickened pericardium in 7 cats and 6 dogs. Clinical signs of pleural fluid accumulation resolved in 10 of 10 dogs and in 8 of 10 cats after surgery. The overall success rate for the surgical treatment of chylothorax (ie, the resolution of pleural fluid accumulation) in this study was 90% (100% in dogs and 80% in cats). These data suggest that TD ligation in conjunction with pericardectomy has a favorable outcome in animals with idiopathic chylothorax.

Chylothorax is a devastating disease, and the success rates from either medical or surgical management are less than satisfactory. In some animals with chylothorax, a thickening of the pericardium occurs that is associated with chronic irritation induced by chyle. We hypothesized that pericardial thickening would lead to increased right-sided venous pressures and that abnormal venous pressures would act to impede the drainage of chyle via lymphaticovenous communications after thoracic duct (TD) ligation. We also hypothesized that serosanguineous effusions that occurred after TD ligation could effectively be treated or prevented by pericardectomy in affected animals. TD ligation plus pericardectomy was performed in 17 animals, and pericardectomy alone was performed in an additional 3 animals that presented during a 5.5-year period to the Texas A&M University (College Station, TX). Nineteen animals presented for an evaluation of idiopathic chylothorax (9 dogs and 10 cats), and 1 dog presented for serosanguineous pleural fluid after TD ligation that had been performed elsewhere. Echocardiography was normal in all animals, except for a subjectively thickened pericardium in 7 cats and 6 dogs. Clinical signs of pleural fluid accumulation resolved in 10 of 10 dogs and in 8 of 10 cats after surgery. The overall success rate for the surgical treatment of chylothorax (ie, the resolution of pleural fluid accumulation) in this study was 90% (100% in dogs and 80% in cats). These data suggest that TD ligation in conjunction with pericardectomy has a favorable outcome in animals with idiopathic chylothorax.

Endothelial dysfunction (ED) is characterized by impaired nitric oxide (NO) signaling, decreased NO-dependent vasodilatation, increased vascular inflammation, and diminished response to angiogenic factors. TP508 (Chrysalin), an angiogenic tissue repair peptide, was tested for potential effects on myocardial revascularization and ED using a porcine model of chronic myocardial ischemia. TP508 increased perfusion in ischemic regions up to16-fold (P < .02) and doubled myocardial wall thickening (P < .02) relative to placebo controls. Ischemic arterioles exhibited impaired NO-mediated vasodilation and diminished NO production. TP508 reversed ischemic effects, increasing NO-mediated vasodilation (P < .05), endothelial nitric oxide synthase (eNOS) expression, and NO production. In human endothelial cells, TP508 stimulated eNOS activation (1.84 +/- 0.2-fold; P < .02), increased NO production (85 +/- 18%; P < .02), and prevented hypoxia-induced eNOS downregulation (P < .01). Thus, TP508 reverses ED both in porcine ischemic hearts and cultured human endothelial cells. These results suggest potential therapeutic benefit of TP508 in myocardial revascularization and treatment of ED-related diseases.

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