Replacement of infected aortoiliac vascular grafts with bifurcated BioIntegral Surgical No-React® bovine pericardial xenografts.

The infection of a vascular prosthesis is potentially fatal, and its effective treatment still remains the greatest challenge for vascular surgeons. We present our initial experience using bovine pericardial vascular prostheses to replace infected aortoiliac vascular grafts. Six consecutive patients with infection of the graft were prospectively included in this study. Infection of the vascular graft was confirmed by clinical symptoms, laboratory tests and the results of computed tomography and positron emission tomography/computed tomography. In all cases, the infected aortoiliac graft was surgically removed and replaced by the bovine-pericardial BioIntegral aortic-bifemoral prosthesis. Technical success was achieved in every case with no in-hospital or 30 days mortality. One patient required revision of distal anastomosis due to recurrent bleeding at day four after surgery. One patient presented with upper gastrointestinal tract bleeding during the postoperative period, which was managed endoscopically. The mean hospital stay was 14 days (range 9-19). The control CT scan performed 2 months after surgery showed significant regression of abscesses and periprosthetic inflammation. Two patients died within 32 months of follow-up: one due to heart attack, the other due to generalized sepsis, which was correlated with the previous infection. Four patients are still in follow-up. The BioIntegral prosthesis is patent in all four cases, with no clinical or ultrasonographic signs of infection. Our brief investigation shows that a bovine pericardial prosthesis may be a valuable option in the treatment of vascular grafts infections.

Metabolic Effects of Metformin in the Failing Heart.

Accumulating evidence shows that metformin is an insulin-sensitizing antidiabetic drug widely used in the treatment of type 2 diabetes mellitus (T2DM), which can exert favorable effects on cardiovascular risk and may be safely used in patients with heart failure (HF), and even able to reduce the incidence of HF and to reduce HF mortality. In failing hearts, metformin improves myocardial energy metabolic status through the activation of AMP (adenosine monophosphate)-activated protein kinase (AMPK) and the regulation of lipid and glucose metabolism. By increasing nitric oxide (NO) bioavailability, limiting interstitial fibrosis, reducing the deposition of advanced glycation end-products (AGEs), and inhibiting myocardial cell apoptosis metformin reduces cardiac remodeling and hypertrophy, and thereby preserves left ventricular systolic and diastolic functions. While a lot of preclinical and clinical studies showed the cardiovascular safety of metformin therapy in diabetic patients and HF, to confirm observed benefits, the specific large-scale trials configured for HF development in diabetic patients as a primary endpoints are necessary.

Tempol, a Membrane-Permeable Radical Scavenger, Exhibits Anti-Inflammatory and Cardioprotective Effects in the Cerulein-Induced Pancreatitis Rat Model.

To date, it remains unclear whether mild form of acute pancreatitis (AP) may cause myocardial damage which may be asymptomatic for a long time. Pathogenesis of AP-related cardiac injury may be attributed in part to ROS/RNS overproduction. The aim of the present study was to evaluate the oxidative stress changes in both the pancreas and the heart and to estimate the protective effects of 1-oxyl-2,2,6,6-tetramethyl-4-hydroxypiperidine (tempol) at the early phase of AP. Cerulein-induced AP led to the development of acute edematous pancreatitis with a significant decrease in the level of sulfhydryl (-SH) groups (oxidation marker) both in heart and in pancreatic tissues as well as a substantial increase in plasma creatine kinase isoenzyme (CK-MB) activity (marker of the heart muscle lesion) which confirmed the role of oxidative stress in the pathogenesis of cardiac damage. The tempol treatment significantly reduced the intensity of inflammation and oxidative damage and decreased the morphological evidence of pancreas injury at early AP stages. Moreover, it markedly attenuated AP-induced cardiac damage revealed by normalization of the -SH group levels and CK-MB activity. On the basis of these studies, it is possible to conclude that tempol has a profound protective effect against cardiac and pancreatic damage induced by AP.

Patients' satisfaction with therapy methods of advanced chronic venous disease.

BACKGROUND: To assess patients' satisfaction from the therapy of advanced chronic venous disorders (CVD) in everyday clinical practice in Poland, and to compare the efficacy of various venoactive drugs (VADs) in venous ulcers healing process. METHODS: Seven hundred and eighty unselected adult patients with active (N.=441) or healed (N.=339) venous ulcers participated in the non-interventional observational 6-week study. RESULTS: Compression therapy and VADs were utilized by 81.5% and 89.2% of patients respectively: 31.2% of all patients underwent surgical procedures for vein incompetence, 61.3% were satisfied with surgical methods, 43% with compression therapy, and 32.6% with VADs ­ with highest rate of satisfied patients in the group taking Ruscus aculeatus and HMC and ascorbic acid (51.4%). Of 377 patients with active venous ulcers smaller than 200 cm2, adherent to VADs, 18.0% have been cured, and 66.6% have improved during 6-week period of observation. Multiple logistic regression analysis revealed that the compression therapy (OR=2.74), the size of ulcer ≤10 cm2 (OR=2.70) were increasing the change of ulcer healing. No VADs was better than another in the healing process. CONCLUSION: 1) Compression therapy and VADs are highly utilized by patients with advanced CVD. 2) Patients are more satisfied with surgical than conservative treatment of advanced CVD. 3) More than half of the patients with the advanced stage CVD taking Ruscus aculeatus and HMC and ascorbic acid is satisfied with the obtained improvement. 4) Ruscus aculeatus and HMC and ascorbic acid is similarly effective as other frequently used VADs in venous ulcer healing. 5) Ruscus aculeatus and HMC and ascorbic acid exerting effects on veins, capillaries and lymphatic vessels may explain the positive results observed in this study.

Efficacy evaluation of bio trombina ® 400 in mini mall y invasive treatment of complications (pseudoaneurysms), after venipuncture for diagnostic purposes. Authors' own experience - case study of 38 patients.

UNLABELLED: Common use of venipuncture on upper and lower limbs for diagnostic purposes (such as coronarography or arteriography), and also during the course of treatment (angioplasty), very often bares a complication in the form of pseudoaneurysms. According to various reports, the incidence of pseudoaneurysms ranges from 0.005% to 0.5% of all vascular procedures requiring arterial cannulation (Common Femoral Artery, Brachial Artery, Radial Artery). The use of Bio Trombina® 400 in the embolization of pseudoaneurysms allows minimally invasive and effective treatment. The aim of the study was to evaluate the efficacy of pseudoaneurysm embolization with the use of Trombina 400, authors' own experience. MATERIAL AND METHODS: In the years 2011 - 2013, the authors of this study performed 38 vascular interventional procedures involving pseudoaneurysms as complications of venipuncture in upper and lower limbs for diagnostic and treatment purposes. All procedures involved the direct injection of thrombin into the chamber of the pseudoaneurysm under the guidance of USG Doppler (6.2 MHz linear head). 34 cases presented single chamber pseudoaneurysms while 4 cases involved multi- chamber pseudoaneurysms, which required several thrombin reinjections (Bio Trombina® 400) into each of the chambers. Pseudoaneurysm maximum size of 4 cm was set as an inclusion criterion for the embolization procedure. Furthermore, all pseudoaneurysms with a significantly wide tract in transverse dimensions were treated as an exclusion criterion because of high risk of the peripheral arteries embolization. RESULTS: Initial success was observed in 36 patients (94.73%) in the first day after the procedure, 1 patient (2.63%) underwent thrombin reinjection procedure in the second day after the first embolization. Another patient (2.63%) underwent an open procedure in which the Common Femoral Artery was accessed, the clot evacuated, and CFA was sutured with continuous suture Prolene 6-0. CONCLUSIONS: 1. Embolization of pseudoaneurysms with USG Doppler-guided thrombin injection is an effective course of treatment for complications of cannulation. 2. The safety of pseudoaneurysm embolization depends on a surgeon's experience. It is also crucial to keep in mind the inclusion and exclusion criteria for this type of procedure (the size of a pseudoaneurysm, the width of its base). 3. Furthermore, its cost effectiveness and short hospitalization period make pseudoaneurysm embolization an effective and valuable alternative to the classic approach.

Nucleoside monophosphorothioates as the new hydrogen sulfide precursors with unique properties.

Hydrogen sulfide (H2S) is the gasotransmitter enzymatically synthesized in mammalian tissues from l-cysteine. H2S donors are considered as the potential drugs for the treatment of cardiovascular, neurological and inflammatory diseases. Recently, it has been demonstrated that synthetic nucleotide analogs, adenosine- and guanosine 5'-monophosphorothioates (AMPS and GMPS) can be converted to H2S and AMP or GMP, respectively, by purified histidine triad nucleotide-binding (Hint) proteins. We examined if AMPS and GMPS can be used as the H2S donors in intact biological systems. H2S production by isolated rat kidney glomeruli was measured by the specific polarographic sensor. H2S production was detected when glomeruli were incubated with AMPS or GMPS and ionotropic purinergic P2X7 receptor/channel agonist, BzATP. More H2S was generated from GMPS than from equimolar amount of AMPS. Nucleoside phosphorothioates together with BzATP relaxed angiotensin II-preconstricted glomeruli. In addition, infusion of AMPS or GMPS together with BzATP into the renal artery increased filtration fraction and glomerular filtration rate but had no effect on renal vascular resistance or renal blood flow. AMPS but not GMPS was converted to adenosine by isolated glomeruli, however, adenosine was not involved in AMPS-induced H2S synthesis because neither adenosine nor specific adenosine receptor agonists had any effect on H2S production. AMPS, but not GMPS, increased phosphorylation level of AMP-stimulated protein kinase (AMPK), but AMPK inhibitor, compound C, had no effect on AMPS-induced H2S production. In conclusion, nucleoside phosphorothioates are converted to H2S which relaxes isolated kidney glomeruli in vitro and increases glomerular filtration rate in vivo. AMPS and GMPS can be used as the H2S donors in experimental studies and possibly also as the H2S-releasing drugs.

Chronic hyperleptinemia induces resistance to acute natriuretic and NO-mimetic effects of leptin.

Apart from controlling energy balance, leptin, secreted by adipose tissue, is also involved in the regulation of cardiovascular function. Previous studies have demonstrated that acutely administered leptin stimulates natriuresis and vascular nitric oxide (NO) production and that these effects are impaired in obese animals. However, the mechanism of resistance to leptin is not clear. Because obesity is associated with chronically elevated leptin, we examined if long-term hyperleptinemia impairs acute effects of leptin on sodium excretion and NO production in the absence of obesity. Hyperleptinemia was induced in lean rats by administration of exogenous leptin at a dose of 0.5mg/kg/day for 7 days, and then acute effect of leptin (1mg/kg i.v.) was studied under general anesthesia. Leptin increased fractional sodium excretion and decreased Na(+),K(+)-ATPase activity in the renal medulla. In addition, leptin increased the level of NO metabolites and cyclic GMP in plasma and aortic wall. These acute effects of leptin were impaired in hyperleptinemic animals. In both control and hyperleptinemic groups the effect of leptin on Na(+) excretion and renal Na(+),K(+)-ATPase was abolished by phosphoinositide 3-kinase (PI3K) inhibitor, wortmannin, but not by protein kinase B/Akt inhibitor, triciribine,. In contrast, acute effect of leptin on NO metabolites and cGMP was abolished by triciribine but not by wortmannin. Leptin stimulated Akt phosphorylation at Ser(473) in aortic tissue but not in the kidney, and this effect was comparable in control and hyperleptinemic groups. These results suggest that hyperleptinemia may mediate "renal" and "vascular" leptin resistance observed in obesity.

Renal antioxidant enzymes and glutathione redox status in leptin-induced hypertension.

Previously, we have demonstrated that leptin increases blood pressure (BP) in the rats through two oxidative stress-dependent mechanisms: stimulation of extracellular signal-regulated kinases (ERK) by H(2)O(2) and scavenging of nitric oxide (NO) by superoxide (O(2-.)). Herein, we examined if renal glutathione system and antioxidant enzymes determine the mechanism of prohypertensive effect of leptin. Leptin administered at 0.5 mg/kg/day for 4 or 8 days increased BP and renal Na(+),K(+)-ATPase activity and reduced fractional sodium excretion; these effects were prevented by NADPH oxidase inhibitor, apocynin. Superoxide scavenger, tempol, abolished the effect of leptin on BP and renal Na(+) pump in rats receiving leptin for 8 days, whereas ERK inhibitor, PD98059, was effective in animals treated with leptin for 4 days. Leptin administered for 4 days decreased glutathione (GSH) and increased glutathione disulfide (GSSG) in the kidney. In animals receiving leptin for 8 days GSH returned to normal level, which was accompanied by up-regulation of gamma-glutamylcysteine synthetase (gamma-GCS), a rate-limiting enzyme of the GSH biosynthetic pathway. In addition, superoxide dismutase (SOD) activity was decreased, whereas glutathione peroxidase (GPx) was increased in rats receiving leptin for 8 days. Cotreatment with gamma-GCS inhibitor, buthionine sulfoximine (BSO), accelerated, whereas GSH precursor, N-acetylcysteine (NAC), attenuated leptin-induced changes in gamma-GCS, SOD, and GPx. In addition, coadministration of BSO changed the mechanism of BP elevation from H(2)O(2)-ERK to (O(2-.))-NO dependent in animals receiving leptin for 4 days, whereas NAC had the opposite effect in rats treated with leptin for 8 days. These results suggest that initial change in GSH redox status induces decrease in SOD/GPx ratio, which results in greater amount of (O)2-.)) versus H(2)O(2) in later phase of leptin treatment, thus shifting the mechanism of BP elevation from H(2)O(2)-ERK to (O(2-.))-NO dependent.