RESUMO
Mitral valve and aortic valve regurgitation associated with enlarged left ventricle remains difficult to manage and the long-term results following surgical treatment is uncertain. Between April 1988 and September 2000, 82 patients with aortic and mitral regurgitation associated with enlarged left ventricle underwent valve replacement at Anzhen Hospital. The valve disease was rheumatic in origin in 75 patients (91.5%) and congenital in 7 (8.5%). Twenty-eight patients were in New York heart Association Functional (NYHA) class II and 39 in class III and 15 in class IV. Echocardiogram showed severe aortic insufficiency associated with mild to moderate mitral regurgitation in 66 patients and severe mitral regurgitation associated with mild to moderate AI in 16 patients. The mean left ventricular diastole diameter (LVDD) was 77.8 ± 5.2 mm. Valve replacement was performed under hypothermic cardiopulmonary bypass (CPB). Early hospital mortality was 7.3%. Two weeks after surgery the echocardiogram showed a reduction of LVDD. Follow up was completed in 69 patients with mean of 13.5 years. 20 patients were in NYHA class I; 26 in Class II and 3 in Class III and 2 in class IV. The follow-up survival rate was 73.9%, and follow-up mortality was 26.1%. LVDD reduced from 77.8 ± 5.2 mm to 58.3 ± 4.5 mm (P < 0.001). In 24 patients, the LVDD was less than 50 mm. Double valve replacement and/or repair carried out an acceptable early and Long-term clinical outcomes in patients with MR and AI with associated LV great enlargement. Both LVDD and NYHA improved following surgical treatment in survival patients.
RESUMO
Hypoxia inducible factor-1 (HIF-1) has been considered as a critical transcriptional factor in response to hypoxia. It can increase P-glycoprotein (P-Gp) thus generating the resistant effect to chemotherapy. At present, the mechanism regulating HIF-1α is still not fully clear in hypoxic tumor cells. Intracellular redox status is closely correlated with hypoxic micro-environment, so we investigate whether alterations in the cellular redox status lead to the changes of HIF-1α expression. HepG2 cells were exposed to Buthionine sulphoximine (BSO) for 12 h prior to hypoxia treatment. The level of HIF-1α expression was measured by Western blot and immunocytochemistry assays. Reduce glutathione (GSH) concentrations in hypoxic cells were determined using glutathione reductase/5,5'-dithiobis-(2-nitrob-enzoic acid) (DTNB) recycling assay. To further confirm the effect of intracellular redox status on HIF-1α expression, N-acetylcysteine (NAC) was added to culture cells for 8 h before the hypoxia treatment. The levels of multidrug resistance gene-1 (MDR-1) and erythropoietin (EPO) mRNA targeted by HIF-1α in hypoxic cells were further determined with RT-PCR, and then the expression of P-Gp protein was observed by Western blotting. The results showed that BSO pretreatment down-regulated HIF-1α and the effect was concentration-dependent, on the other hand, the increases of intracellular GSH contents by NAC could partly elevate the levels of HIF-1α expression. The levels of P-Gp (MDR-1) and EPO were concomitant with the trend of HIF-1α expression. Therefore, our data indicate that the changes of redox status in hypoxic cells may regulate HIF-1α expression and provide valuable information on tumor chemotherapy.
