Objectives. We evaluated whether the reported difference in the ventricular defibrillation threshold (DFT) between short-term intravenous and oral amiodarone is due to the effect of amiodarone’s active metabolite desethylamiodarone (DEA).
Background. Amiodarone is frequently used in patients with implantable cardioverter-defibrillator devices (ICD). Long-term oral amiodarone raises the DFT, but intravenous amiodarone has not been shown to have this effect. DEA, an active metabolite of amiodarone, has different electrophysiologic properties than its parent compound and may be responsible for the observed different effects of intravenous and oral amiodarone on DFT.
Methods. We ascertained the DFT in 24 pigs randomized to receive intravenous amiodarone, DEA or vehicle. Defibrillation was delivered through a transvenous lead system using a biphasic waveform. The DFT was determined using an up-down DFT algorithm and defined as the average minimal energies resulting in successful defibrillation delivered from ascending and descending serial shocks.
Results. Amiodarone caused a dose-response increase in DFT (mean ± SD) from 22.7 ± 4.1 (baseline) to 26.1 ± 2.9 (10 mg/kg body weight), p = 0.11, to 34.9 ± 8.2 J (after an additional 15 mg/kg), p = 0.035. DEA (10 mg/kg) caused an increase in DFT from 20.5 ± 6.3 to 33.9 ± 13.6 J, p < 0.01. Addition of 15 mg/kg of DEA resulted in hemodynamic instability and thus DFT was not obtained. In the control group, DFT decreased from 26.8 ± 7.7 at baseline to 23.1 ± 7.4 (dose 1), p = 0.19, to 22.8 ± 6.2 J (dose 2), p = 0.18.
Conclusions. DEA increases DFT by a greater amount than its parent drug amiodarone. There is an effect of intravenous amiodarone on DFT that is dose dependent. 相似文献
BackgroundInvestigate the effects of Stellera chamaejasme on microvascular density and apoptosis of cancer cells in rat bladder tumor models.MethodsThe bladder tumor model of 75 specific pathogen-free (SPF)-grade Sprague-Dawley (SD) rats aged 5–6 weeks was established by n-methyl-N-nitrosourea (MNU) bladder perfusion induction, and the model rats were randomly divided into model group, low-dose (L-dose) group, medium-dose (M-dose) group, high-dose (H-dose) group, and positive drug (hydroxycamptothecine, HCPT) group. L-dose group, M-dose group, and H-dose group were treated with 5 g/kg, 10 g/kg, and 20 g/kg, respectively. The HCPT group was treated with 2 mg/kg hydroxycamptothecin at 1 mL/kg once a week and the model group were treated with the same amount of normal saline for 4 weeks. The quality of bladder cancer tissues in each group was measured. The pathological changes and microvascular density of bladder tissues were observed, and the apoptosis rate of vascular endothelial growth factor (VEGF), tumor tissue and the protein expression levels of factor associated suicide (Fas), factor associated suicide ligand (FasL) and Caspase3 in bladder tissues were detected.ResultsBladder cancer was induced 14 weeks after initial bladder perfusion with MNU. In the model group, epithelial cells of bladder tissue showed atypically hyperplasia with various sizes and disorders. After treatment with Stellera chamaejasme, the hematoxylin-eosin (HE) scores, bladder weight, microvascular density, and VEGF were significantly decreased, and the tumor inhibition rate, cell apoptosis, and the expression of apoptosis-related proteins Fas, FasL, and Caspase3 were significantly increased in the bladder tissue. The above changes were dose-dependent with Stellera chamaejasme.ConclusionsMNU can be used to prepare a rat bladder cancer model. Stellera chamaejasme has a good therapeutic effect on rat bladder cancer, which may inhibit the progression of bladder cancer by inhibiting micro-angiogenesis and inducing the apoptosis of bladder tumor cells. 相似文献
Clinical Rheumatology - To evaluate the serum levels of the anti-inflammatory cytokine interleukin-10 (IL-10) in patients with adult-onset Still’s disease (AOSD), a rare, systemic, and... 相似文献