Przepływ w gałęzi przedniej zstępującej lewej tętnicy wieńcowej u pacjentów z marskością wątroby

Introduction. Although cardiac function appears normal in patients with cirrhosis at rest, cardiac function deteriorates in these patients under stress conditions. Decreased cardiac function against stress may be due to coronary microvascular dysfunction in these patients. In this study, we aimed to evaluate coronary microvascular dysfunction in patients with cirrhosis by measuring coronary flow reserve (CFR) by transthoracic echocardiography. Materials and methods. Thirty-eight patients with cirrhosis and 32 healthy subjects (as control group) were examined. In addition to standard two-dimesional (2D) and Doppler echocardiography, coronary flow velocity was measured by pulsed-wave Doppler from the middle to the distal part of the left anterior descending artery at the beginning and after dipyridamole infusion in the hyperemic state. CFR was measured as the ratio of hyperemic peak diastolic flow rate to basal peak diastolic flow rate. Results. CFR was significantly lower in the cirrhosis group than in the control group (2.01 ± 0.31 and 2.84 ± 0.62; p < 0.0001). Increasing age, increasing myocardial mass, high aspartate aminotransferase and alanine aminotransferase, low hemoglobin, high C-reactive protein, decreased cholesterol and platelet levels were found to be associated with the reduction in CFR. Among all these factors only, the hemoglobin level and age were independent determinants of impaired CFR. Conclusions. Impaired CFR in patients with cirrhosis promotes coronary microvascular dysfunction. The coronary microvascular dysfunction can potentially contribute to the development of cirrhotic cardiomyopathy.Wstęp. Chociaż czynność serca u pacjentów z marskością wątroby oceniana w spoczynku wydaje się prawidłowa, to w warunkach wysiłku fizycznego lub obciążenia farmakologicznego ulega ona pogorszeniu. Zaburzenie czynności serca podczas obciążenia może być spowodowane dysfunkcją mikrokrążenia wieńcowego u tych chorych. Celem badania była ocena dysfunkcji mikrokrążenia wieńcowego u pacjentów z marskością wątroby przez pomiar rezerwy przepływu wieńcowego (CRF) za pomocą echokardiografii przezklatkowej. Materiał i metody. Do badania włączono 38 chorych z marskością wątroby i 32 osoby zdrowe (grupa kontrolna). Oprócz standardowej echokardiografii dwuwymiarowej (2D) i echokardiografii doplerowskiej prędkość przepływu wieńcowego w odcinkach środkowym i dystalnym gałęzi przedniej lewej tętnicy zstępującej zmierzono za pomocą badania dopplerowskiego metodą fali pulsacyjnej bezpośrednio przed wlewem dipirydamolu i po nim. Rezerwę przepływu wieńcowego mierzono jako stosunek maksymalnego przepływu rozkurczowego w obciążeniu do maksymalnego przepływu rozkurczowego w spoczynku. Wyniki. Rezerwa przepływu wieńcowego była istotnie niższa w grupie z marskością wątroby niż w grupie kontrolnej (2,01 ± 0,31 i 2,84 ± 0,62; p &lt; 0,0001). Stwierdzono, że ze zmniejszeniem CFR wiązały się: wiek, zwiększenie masy mięśnia sercowego, wysoka aktywność aminotransferaz asparaginianowej i alaninowej, niskie stężenie hemoglobiny, wysokie stężenie białka C-reaktywnego, obniżone stężenie cholesterolu i zmniejszona liczba płytek krwi. Jednak tylko stężenie hemoglobiny i wiek były niezależnymi determinantami zmniejszonej CFR. Wnioski. Zmniejszenie CFR u chorych z marskością wątroby sprzyja dysfunkcji mikrokrążenia wieńcowego, która może prowadzić do rozwoju kardiomiopatii wątrobowej (marskiej)

ADHERE: randomized controlled trial comparing renal function in de novo kidney transplant recipients receiving prolonged-release tacrolimus plus mycophenolate mofetil or sirolimus

ADHERE was a randomized, open-label, Phase IV study comparing renal function at Week 52 postkidney transplant, in patients who received prolongedrelease tacrolimus-based immunosuppressive regimens. On Days 0?27, patients received prolonged-release tacrolimus (initially 0.2 mg/kg/day), corticosteroids, and mycophenolate mofetil (MMF). Patients were randomized on Day 28 to receive either prolonged-release tacrolimus plus MMF (Arm 1) or prolongedrelease tacrolimus (?25% dose reduction on Day 42) plus sirolimus (Arm 2). The primary endpoint was glomerular filtration rate by iohexol clearance (mGFR) at Week 52. Secondary endpoints included eGFR, creatinine clearance (CrCl), efficacy failure (patient withdrawal or graft loss), and patient/graft survival. Tolerability was analyzed. The full-analysis set comprised 569 patients (Arm 1: 287; Arm 2: 282). Week 52 mean mGFR was similar in Arm 1 versus Arm 2 (40.73 vs. 41.75 ml/min/1.73 m2; P = 0.405), as were the secondary endpoints, except composite efficacy failure, which was higher in Arm 2 versus 1 (18.2% vs. 11.5%; P = 0.002) owing to a higher postrandomization withdrawal rate due to adverse events (AEs) (14.4% vs. 5.2%). Results from this study show comparable renal function between arms at Week 52, with fewer AEs leading to study discontinuation with prolonged-release tacrolimus plus MMF (Arm 1) versus lower dose prolonged-release tacrolimus plus sirolimus (Arm 2)

Amifostine enhances the antioxidant and hepatoprotective effects of UW and HTK preservation solutions

AIM: To investigate whether amifostine contributes to the antioxidant and cytoprotective effects of histidine-tryptophan-ketoglutarate (HTK) and University of Wisconsin (UW) preservation solutions. METHODS: Forty-eight Sprague Dawley male rats were equally divided into six groups: (1) ringer Lactate (RL) group; (2) RL + amifostine (RL + A) group; (3) HTK group; (4) HTK + A group; (5) UW group; and (6) UW + A group. Rats in the RL + A, HTK + A and UW + A groups were administered amifostine intraperitoneally at a dose of 200 mg/kg prior to laparotomy. The RL group was perfused with RL into the portal vein. The RL + A group were perfused with RL into the portal vein after amifostine administration. The HTK group received an HTK perfusion while the HTK + A group received an HTK perfusion after administration of amifostine. The UW group received a perfusion of UW, while the UW + A group received a UW perfusion after amifostine administration. Liver biopsy was performed to investigate histopathological, immunochemical [transferase mediated dUTP nick end labeling (TUNEL), inducible nitric oxide syntetase (iNOS)] and ultrastructural alterations. Biochemical alterations were determined by examining levels of alanine aminotransferase, alkaline phosphatase and nitric oxide in the perfusion fluid. RESULTS: Pathological sinusoidal dilatation and centrilobular hydropic alteration were significantly lower in the groups that received amifostine prior to preservation solution perfusion. Although the best results were obtained in the UW + A group, we did not observe a statistically significant difference between the UW + A and HTK + A groups. iNOS grades were significantly lower in the amifostine groups 12 h after treatment. When the amifostine groups were compared against each other, the iNOS grades obtained from the UW + A and HTK + A groups were similar while the RL + A group had a much poorer score. TUNEL assays demonstrated a lower apoptosis ratio in the amifostine groups than in the non-amifostine groups 12 h after treatment. No statistically significant difference was observed between the UW + A and HTK + A groups for apoptosis. Cellular ultrastructure was best preserved in the UW + A and HTK + A groups. CONCLUSION: Here, we show that preoperative administration of a single dose of amifostine is sufficient to minimize the preservation damage in hepatic cells. (C) 2014 Baishideng Publishing Group Inc. All rights reserved

Evaluation of neointimal hyperplasia on tranilast-coated synthetic vascular grafts: An experimental study

Tranilast is an antiallergic drug that interferes with proliferation and migration of vascular smooth muscle cell induced by platelet-derived growth factor (PDGF) and transforming growth factor-beta 1 (TGF-beta 1). We investigated the local effect of tranilast on neointimal hyperplasia using tranilastcoated prosthetic grafts. The inner sides of the thin-walled polytetrafluoroethylene (PTFE) grafts were coated with chitosan and tranilast containing chitosan solution. Wistar albino rats (32) were used in the study. Patches (1 x 2 mm) for vascular grafts were prepared. Three groups were tested: group 1 (n = 12; tranilast coated), group 2 (n = 10; adhesive-only film-layer-coated), and group 3 (n = 10; normal ePTFE patch grafts sutured to the carotid arteries of the rats). Recipient sites of the carotid arteries were excised 4 weeks after surgery. All sections were examined histologically for graft patency, thrombus formation, and neointimal thickness. Expression of PDGF, fibroblast growth factor, and TGF-beta 1 on cross-sections of the neointima were evaluated by immunohistochemistry. No significant differences were found regarding mean neointimal thicknesses. PDGF and TGF-beta-1 expressions were significantly lower in group 1. Although a decrease in local effect of tranilast was observed for growth factor expressions at a drug concentration of 0.05 mg/cm(2), a significant reduction in neointimal hyperplasia was not achieved. The coating concentration of 0.05 mg/cm(2) may have been too low to produce an antiproliferative effect. Given our promising results, further studies are recommended and planned using different drug concentrations and time intervals