L-carnitine protects against cyclosporine-induced pancreatic and renal injury in rats.

BACKGROUND: L-carnitine has protective effects against various types of injury. This study was designed to evaluate the beneficial effects of L-carnitine on pancreatic and renal injuries caused by cyclosporine (CsA). METHODS: Rats maintained on a low sodium diet were given vehicle (olive oil, 1 mL/kg/d), CsA (15 mg/kg/d), L-carnitine (50 or 200 mg/kg/d), or a combination of CsA and L-carnitine for 4 weeks. The impact of L-carnitine on pancreatic injury was assessed by blood glucose levels, plasma insulin concentrations, and hemoglobulin A1c (HbA1c). In addition, the protective effects of L-carnitine against CsA-induced kidney injury were evaluated in terms of renal function, histopathology (inflammatory cell influx and tubulointerstitial fibrosis), oxidative stress (8-hydroxy 2'-deoxyguanosine, 8-OHdG), transforming growth factor-betal (TGF-ß1), apoptosis (caspase-3), and autophagy (LC3-II). RESULTS: CsA treatment caused diabetes, renal dysfunction, tubulointerstitial inflammation (ED-1-positive cells), and fibrosis, which were accompanied by an increase in 8-OHdG production and upregulation of TGF-ß1, caspase-3, and LC3-II. Concomitant administration of L-carnitine increased plasma insulin concentrations, decreasing plasma glucose and HbA1c levels. In the kidney, L-carnitine induced dose-dependent improvement of renal function, inflammation, and fibrosis in parallel with suppression of the expression of TGF-ß1 and 8-OHdG. Furthermore, the administration of L-carnitine at a high dose inhibited the expression of caspase-3 and LC3-II. CONCLUSION: These findings suggest that L-carnitine has a protective effect against CsA-induced pancreatic and renal injuries.

Ascorbate attenuates atrial pacing-induced peroxynitrite formation and electrical remodeling and decreases the incidence of postoperative atrial fibrillation.

Atrial fibrillation (AF), the most common chronic arrhythmia, increases the risk of stroke and is an independent predictor of mortality. Available pharmacological treatments have limited efficacy. Once initiated, AF tends to self-perpetuate, owing in part to electrophysiological remodeling in the atria; however, the fundamental mechanisms underlying this process are still unclear. We have recently demonstrated that chronic human AF is associated with increased atrial oxidative stress and peroxynitrite formation; we have now tested the hypothesis that these events participate in both pacing-induced atrial electrophysiological remodeling and in the occurrence of AF following cardiac surgery. In chronically instrumented dogs, we found that rapid (400 min(-1)) atrial pacing was associated with attenuation of the atrial effective refractory period (ERP). Treatment with ascorbate, an antioxidant and peroxynitrite decomposition catalyst, did not directly modify the ERP, but attenuated the pacing-induced atrial ERP shortening following 24 to 48 hours of pacing. Biochemical studies revealed that pacing was associated with decreased tissue ascorbate levels and increased protein nitration (a biomarker of peroxynitrite formation). Oral ascorbate supplementation attenuated both of these changes. To evaluate the clinical significance of these observations, supplemental ascorbate was given to 43 patients before, and for 5 days following, cardiac bypass graft surgery. Patients receiving ascorbate had a 16.3% incidence of postoperative AF, compared with 34.9% in control subjects. In combination, these studies suggest that oxidative stress underlies early atrial electrophysiological remodeling and offer novel insight into the etiology and potential treatment of an enigmatic and difficult to control arrhythmia. The full text of this article is available at http://www.circresaha.org.

[The effects of transcutaneous electrical stimulation during sleep on obstructive sleep apnea].

OBJECTIVE: To study the effects of transcutaneous electrical stimulation during sleep on obstructive sleep apnea syndrom (OSAS). METHOD: Sixteen patients with OSAS were studied by polysomnography during all-night sleep with and without submental transcutaneous electrical stimulation (TES) of the genioglossus. RESULT: Fourteen of the 16 patients (87%) who accepted the TES were treated successfully (reduction of Al > 50%). The average apnea index showed a decrease of 29 events per hour when the TES were performed (P < 0.001). The average apnea time decreased from 22 to 7 sec (P < 0.001). The apnea time/TST decreased from 27% +/- 11% to 7% +/- 3%. The lowest SaO2 increased from 71% to 87% (P < 0.001). TES did not cause arousal. The sleep stages of SWS, and REM sleep effect (SE) increased significantly. CONCLUSION: TES is a conservative but effective treatment in patients with obstructive sleep apnea syndrome, although it failed to improve central sleep apnea.

[Protective effects of methanolic extract of Oenanthe stolonifera (Roxb.) Wall. ex DC. on myocardial injury induced by ischemia and reperfusion in rats].

The methanolic extract Oenanthe stoloni fera iv, pretreatment can significantly prevent the arrhythmias induced by myocardial ischemia and reduce the myocardial infarct size in rats. It can also markedly prevent myocardial ischemia and reperfusion-induced arrhythmias. In addition, the methanolic extract of Oenanthe stoloni fera (100 mg/kg i.v.) helps significantly to decrease the MDA content and preserve the SOD activity in plasma.