RESUMEN
We showed recently that increasing kidney epoxyeicosatrienoic acids (EETs) by blocking soluble epoxide hydrolase (sEH), an enzyme responsible for EETs degradation, retarded the development of renal dysfunction and progression of aorto-caval fistula(ACF)-induced congestive heart failure (CHF) in Ren-2 transgenic hypertensive rats (TGR). In that study the final survival rate of untreated ACF TGR was only 14 % but increased to 41 % after sEH blockade. Here we examined if sEH inhibition added to renin-angiotensin system (RAS) blockade would further enhance protection against ACF-induced CHF in TGR. The treatment regimens were started one week after ACF creation and the follow-up period was 50 weeks. RAS was blocked using angiotensin-converting enzyme inhibitor (ACEi, trandolapril, 6 mg/l) and sEH with an sEH inhibitor (sEHi, c-AUCB, 3 mg/l). Renal hemodynamics and excretory function were determined two weeks post-ACF, just before the onset of decompensated phase of CHF. 29 weeks post-ACF no untreated animal survived. ACEi treatment greatly improved the survival rate, to 84 % at the end of study. Surprisingly, combined treatment with ACEi and sEHi worsened the rate (53 %). Untreated ACF TGR exhibited marked impairment of renal function and the treatment with ACEi alone or combined with sEH inhibition did not prevent it. In conclusion, addition of sEHi to ACEi treatment does not provide better protection against CHF progression and does not increase the survival rate in ACF TGR: indeed, the rate decreases significantly. Thus, combined treatment with sEHi and ACEi is not a promising approach to further attenuate renal dysfunction and retard progression of CHF.
Asunto(s)
Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Benzoatos/uso terapéutico , Insuficiencia Cardíaca/tratamiento farmacológico , Indoles/uso terapéutico , Insuficiencia Renal/prevención & control , Urea/análogos & derivados , Animales , Fístula Arteriovenosa , Benzoatos/farmacología , Evaluación Preclínica de Medicamentos , Quimioterapia Combinada , Epóxido Hidrolasas/antagonistas & inhibidores , Femenino , Insuficiencia Cardíaca/complicaciones , Insuficiencia Cardíaca/mortalidad , Masculino , Ratas , Ratas Sprague-Dawley , Ratas Transgénicas , Insuficiencia Renal/etiología , Urea/farmacología , Urea/uso terapéuticoRESUMEN
The goal of the paper is to refer to and to inform about our own experiences with the Sub-Tenon's anesthesia in the surgery of the anterior as well as posterior segment of the eye. In cataract surgery it is equally efficient as the retrobulbar, peribulbar or topic anesthesia, and it is safer because no sharp needle is used. We operate on the posterior segment in sub-Tenon's anesthesia in patients with contraindicated general anesthesia because of their advanced age, decompensated diabetes mellitus or hypertension, in whom the pars plana vitrectomy is the only possibility to improve the patients' vision. Using the sub-Tenon's anesthesia, about 13.000 cataract surgeries and 127 pars plana vitrectomies without complications were performed. The simple pars plana vitrectomy may be realized at the outpatient basis as well.