TP508 (Chrysalin) reverses endothelial dysfunction and increases perfusion and myocardial function in hearts with chronic ischemia.

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.

Surgical correction of subaortic stenosis via right ventriculotomy and septal resection in a dog.

After 2 years of medical management with a beta-adrenoreceptor blocking agent, a 30-month-old castrated male Golden Retriever with subaortic stenosis was treated surgically because of progression of its condition. In an attempt to achieve complete relief of the left ventricular outflow obstruction, a modified Konno procedure consisting of right ventriculotomy and septal myectomy from the infundibular portion of the right ventricle was performed; this combination of procedures allowed wide resection of the septal portion of the left ventricular outflow obstruction. Two years after surgery, the mass of the dog's left ventricle had decreased and the peak calculated pressure gradient across the aortic valve had decreased to 40 mm Hg, compared with a preoperative value of 240 mm Hg; at that evaluation, the dog had gained weight and was able to play normally. It is suggested that use of this modified approach to the outflow tract may have a positive effect on long-term survival time in dogs with subaortic stenosis.

Thoracic duct ligation and pericardectomy for treatment of 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.