An antioxidant tetrapeptide UPF1 in rats has a neuroprotective effect in transient global brain ischemia.

Different glutathione analogues have potential to maintain or increase tissue glutathione level and to scavenge the reactive oxygen species. We designed and synthesized a novel non-toxic glutathione analogue, named UPF1, which possessed 60-fold higher hydroxyl radical scavenger efficiency in vitro, compared with glutathione itself, and investigated the effects of UPF1 on a four-vessel occlusion model of rats. The UPF1 was administered via the jugular vein in two separate experiments at two time points: 20 min before global brain ischemia and immediately before reperfusion. In both cases the number of pyramidal cells surviving in the subfield of CA1 at the dorsal hippocampus in the UPF1-treated groups of rats was twice as high as in the vehicle group.

Primary aortoduodenal fistula: successful grafting with axillo-bifemoral bypass.

Primary aortoduodenal fistula (PADF) is uncommon direct pathological communication between the abdominal aorta and duodenum, which may cause life-threatening gastrointestinal bleeding. PADF leads to high mortality and morbidity unless it is promptly evaluated and appropriate surgical intervention performed. We present a case report describing PADF treated successfully with axillobifemoral bypass. A 70-year-old male was admitted in our hospital with severe back and abdominal pain. A pulsative tumor mass was palpated in the middle abdomen. Previous ultrasonography had shown abdominal aortic aneurysm. There were no symptoms of active gastrointestinal bleeding, but the patient had moderate anaemia. Computer tomography revealed infrarenal abdominal aortic aneurysm. Intraoperatively, PADF was diagnosed. The duodenum was repaired and the abdominal aorta was closed directly below the renal arteries. At the next stage, extra-anatomic grafting was performed, because frank pus was found in the abdominal cavity. By present time, the axillobifemoral bypass has been patent for 2 years.

Is elective abdominal aortic aneurysm repair accompanied by high grade oxidative stress?

BACKGROUND AND AIMS: During elective abdominal aortic aneurysm repair (AAAR), lower torso ischaemia-reperfusion event is unavoidable. Previous studies on AAAR have reported the importance of oxidative stress (OS) in ischaemia-reperfusion injury, however, the grade of OS has not been adequately clarified up to now. The aim of this study was to perform a complex investigation of the time-course and grade of systemic and cellular OS in patients undergoing AAAR. MATERIAL AND METHODS: Arterial blood samples were taken from 18 patients undergoing elective AAAR (at four points in time: before anaesthesia, 5 min after aortic clamping and 5 min and 30 min after clamp removal). Diene conjugates (DC), thiobarbituric acid reactive substances (TBARS), total antioxidative capacity (TAC), glutathione redox ratio (GSSG/GSH), and levels of antioxidative enzymes as superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSHPx) were measured from the radial arterial blood. RESULTS: 30 min after the removal of the aortic cross-clamp, arterial CAT showed significant elevation (96.0 vs 56.9 U/l, p < 0.05); GSHPx was significantly elevated (51.5 vs 39.9 U/g Hgb, p < 0.05) and TAC was decreased (31.4 vs 36.5%, p < 0.05) in comparison with preoperative value. CONCLUSIONS: We found limited alterations of several OS parameters, which do not characterize either systemic or cellular high-grade OS during elective AAAR.

Pharmacokinetic-pharmacodynamic interrelationships of intravenous and oral levosimendan in patients with severe congestive heart failure.

OBJECTIVE: To assess the pharmacokinetic-pharmacodynamic (PK-PD) interrelations after a 6-hour continuous infusion and a 2 mg single oral dose of levosimendan in patients with congestive heart failure (CHF). METHODS: This was an open-label, non-randomized Phase II trial in 29 patients with New York Heart Association (NYHA) class III-IV CHF, comprising 2 study days. On the first day, patients were given 6-hour levosimendan infusion with the dose 0.2 microg/kg/min. After a 1-week washout, the patients received a 2 mg single oral dose of levosimendan. Heart rate-corrected electromechanical systole QS2i was the primary variable. Secondary variables were heart rate (HR), systolic (sBP) and diastolic blood pressure (dBP) and 24-hour ambulatory ECG (Holter). RESULTS: QS2i shortened from 515 ms at baseline to 506 ms at the end of 6-hour infusion (p = 0.007). After 2 mg single dose, QS2i shortened at 2 h after drug intake from 532 ms at baseline to 525 ms (p = 0.006). The effect was similar also at 8 h (532 ms vs 526 ms, p = 0.017). Mean of maximum shortening of QS2i observed during the infusion was 22 ms (p < 0.0001) and 17 ms after 2 mg single oral dose (p < 0.0001). The concentration-effect loops for QS2i showed a clear counter-clockwise hysteresis with both modes of administration. sBP and dBP decreased both during infusion and after 2 mg oral dose. HR remained unchanged during both modes of administration. CONCLUSIONS: Both 6-hour infusion and 2 mg single dose of levosimendan showed that levosimendan possesses moderate inotropic and vasodilatory effects in patients with severe congestive heart failure, which could be described as counter-clockwise hysteresis. It seemed that the vasodilatory effect appeared earlier than the inotropic effect.

Safety and efficacy of a novel calcium sensitizer, levosimendan, in patients with left ventricular failure due to an acute myocardial infarction. A randomized, placebo-controlled, double-blind study (RUSSLAN).

AIMS: To evaluate the safety and efficacy of levosimendan in patients with left ventricular failure complicating acute myocardial infarction. METHODS AND RESULTS: Levosimendan at different doses (0.1-0.4 microg x kg(-1) x min(-1)) or placebo were administered intravenously for 6h to 504 patients in a randomised, placebo-controlled, double-blind study. The primary end-point was hypotension or myocardial ischaemia of clinical significance adjudicated by an independent Safety Committee. Secondary end-points included risk of death and worsening heart failure, symptoms of heart failure and all-cause mortality. The incidence of ischaemia and/or hypotension was similar in all treatment groups (P=0.319). A higher frequency of ischaemia and/or hypotension was only seen in the highest levosimendan dose group. Levosimendan-treated patients experienced lower risk of death and worsening heart failure than patients receiving placebo, during both the 6h infusion (2.0% vs 5.9%; P=0.033) and over 24h (4.0% vs 8.8%; P=0.044). Mortality was lower with levosimendan compared with placebo at 14 days (11.7% vs 19.6%; hazard ratio 0.56 [95% CI 0.33-0.95];P =0.031) and the reduction was maintained at the 180-day retrospective follow-up (22.6% vs 31.4%; 0.67 [0.45-1.00],P =0.053). CONCLUSION: s Levosimendan at doses 0.1-0.2 microg x kg(-1) x min(-1) did not induce hypotension or ischaemia and reduced the risk of worsening heart failure and death in patients with left ventricular failure complicating acute myocardial infarction.