ABSTRACT
INTRODUCTION AND IMPORTANCE: The incidence of acquired Gerbode defect has been increasing due to advances in cardiac imaging technology, and some closure methods have been introduced. PRESENTATION OF CASE: A 58-year-old man developed cardiogenic shock due to acute severe aortic valve regurgitation with an acquired Gerbode defect caused by infective endocarditis. Emergency surgery was performed. A large patch with a 0.4 mm extended-polytetrafluoroethylene (e-PTFE) sheet covered with autologous pericardium was used to close the Gerbode defect, and a bioprosthetic valve was used for aortic valve replacement. CLINICAL DISCUSSION: Large patch closure with 0.4 mm e-PTFE sheet and autologous pericardium for fragile Gerbode defect caused by infective endocarditis might be effective with regard to sturdiness, good fitting to the tissue, and excellent resistance to bacteria. CONCLUSION: We encountered a rare case of cardiogenic shock due to acute severe aortic valve regurgitation and acquired Gerbode defect caused by infective endocarditis. In our case, large-patch closure for perforation in a fragile membranous septum was effective.
ABSTRACT
Tolvaptan is a highly selective and orally effective arginine vasopressin V2 receptor antagonist, and is potentially useful for the treatment of heart failure (HF) patients. However, the renoprotective effect of long-term tolvaptan therapy and its underlying mechanisms remain unknown. We evaluated the effects of chronic treatment with tolvaptan on renal dysfunction, podocyte injury, inflammation, oxidative stress, Rho-kinase, epithelial-mesenchymal transition (EMT), and the extracellular signal-regulated protein kinase (ERK1/2) pathway in the renal cortex of Dahl salt-sensitive hypertensive (DS) rats with end-stage severe HF. DS and Dahl salt-resistant rats were fed a high-salt diet at 6 weeks of age. DS rats were treated with vehicle and tolvaptan (0.05% concentration in diet) from the age of 11 to 18 weeks. Vehicle-treated DS rats developed proteinuria, renal dysfunction, glomerulosclerosis, and interstitial fibrosis, which were ameliorated by tolvaptan without changing blood pressure. Decreased expression of nephrin and podocin and increased desmin-positive area in failing rats were restored by tolvaptan. Upregulation of NAD(P)H oxidase p22(phox), p47(phox), and gp91(phox), EMT markers such as transforming growth factor-ß1, vimentin, and fibronectin expression, and Rho-kinase and ERK1/2 phosphorylation in DS rats were significantly suppressed by tolvaptan. Tolvaptan administration resulted in significant inhibition of tumor necrosis factor-α and monocyte chemoattractant protein-1 expression, and nuclear factor-κB phosphorylation. We concluded that long-term tolvaptan therapy may improve renal dysfunction, glomerulosclerosis, podocyte injury, and inflammation associated with oxidative stress, as well as EMT, ERK, and the Rho-kinase pathway in the failing heart of DS rats. Thus, tolvaptan may be a therapeutic strategy for end-stage severe HF.
Subject(s)
Antidiuretic Hormone Receptor Antagonists , Benzazepines/therapeutic use , Heart Failure/drug therapy , Kidney Cortex/drug effects , Nephrosclerosis/drug therapy , Animals , Antigens, CD/metabolism , Antigens, Differentiation, Myelomonocytic/metabolism , Benzazepines/pharmacology , Chemokine CCL2/metabolism , Chemokine CCL5/metabolism , Drug Evaluation, Preclinical , Epithelial-Mesenchymal Transition/drug effects , Heart Failure/complications , Heart Failure/metabolism , Kidney Cortex/pathology , MAP Kinase Signaling System/drug effects , Male , NADPH Oxidases/metabolism , NF-kappa B/metabolism , Nephrosclerosis/complications , Nephrosclerosis/metabolism , Nephrosclerosis/pathology , Oxidative Stress/drug effects , Podocytes/drug effects , Podocytes/pathology , Rats , Rats, Inbred Dahl , Superoxides/metabolism , Tolvaptan , Tumor Necrosis Factor-alpha/metabolism , rho-Associated Kinases/metabolismABSTRACT
BACKGROUND: SHRSP.Z-Lepr(fa)/IzmDmcr (SHRSP fatty) rats create a new animal model of metabolic syndrome. However, the renoprotective effect of telmisartan therapy and its underlying mechanisms in SHRSP fatty rats remain unknown. We evaluate the effects of long-term telmisartan therapy on renal dysfunction, podocyte injury, inflammation, and transforming growth factor-ß1 (TGF-ß1)/Smad, epithelial-mesenchymal transition (EMT), mitogen-activated protein kinase (MAPK), Rho-kinase, and cell-cycle progression pathway in the renal cortex of SHRSP fatty rats. METHODS: Seven-week-old male SHRSP fatty rats were treated with vehicle, telmisartan, and hydralazine for 8 weeks. Age-matched male Wistar-Kyoto/Izumo rats served as a control group. RESULTS: Vehicle-treated SHRSP fatty rats developed proteinuria and renal dysfunction, which in the telmisartan group was less than the vehicle and hydralazine group without changing blood pressure. Glomerulosclerosis and interstitial fibrosis were impaired in SHRSP fatty rats, and the renal damage in the telmisartan group was less than the vehicle and hydralazine groups. Decreased expression of nephrin and podocin and increased desmin-positive area in SHRSP fatty rats were restored by telmisartan but not hydralazine. TGF-ß1/Smad, EMT marker, MAPK, Rho-kinase, and cell-cycle progression pathways were upregulated in SHRSP fatty rats, and these increased proteins in the telmisartan group were less than the vehicle and hydralazine group. Telmisartan administration resulted in significant suppression in tumor necrosis factor-α expression and nuclear factor-κB phosphorylation. CONCLUSION: Long-term telmisartan therapy may improve renal dysfunction, glomerulosclerosis, podocyte injury, and inflammation associated with EMT, TGF-ß/Smad, MAPK, Rho-kinase pathway in SHRSP fatty rats. Thus, telmisartan may have significant therapeutic potential for metabolic syndrome.