Impact of stable PGI<sub>2</sub>analog iloprost on early graft viability after liver transplantation: a pilot study

Barthel, Erik R.; Rauchfuß, F.; Hoyer, Heike; Habrecht, Olaf; Jandt, Karin; Götz, Max; Voigt, R; Heise, Michael; Marx, Gernot; Settmacher, Utz

doi:10.1111/j.1399-0012.2011.01516.x

Cited by 27 publications

(30 citation statements)

References 51 publications

(53 reference statements)

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“…Complete inclusion and exclusion criteria are displayed in Table 1. According to the experience from the pilot study [14] about 83% of primarily enrolled patients reached respiratory and circulatory stable conditions after LT as precondition for trial medication. To randomize 356 patients after LT written informed consent has to be obtained from about 430 patients fulfilling the study criteria observable before LT.…”

Section: Methodsmentioning

confidence: 99%

“…From 2006 to 2008, we evaluated the impact of the PGI 2 analogue iloprost in 80 liver transplanted patients in a prospective, randomized (1:1), open-label, single-center pilot study [14]. Our data indicate that intravenous administered PGI 2 analogue iloprost (1 ng/kg BW/min) improves the graft function, particularly in the early postoperative period.…”

Section: Introductionmentioning

confidence: 99%

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The PRAISE study: A prospective, multi-center, randomized, double blinded, placebo-controlled study for the evaluation of iloprost in the early postoperative period after liver transplantation (ISRCTN12622749)

Barthel

Rauchfuß

Hoyer³

et al. 2013

BMC Surg

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BackgroundLiver graft dysfunction can deteriorate to complete organ failure and increases perioperative morbidity and mortality after liver transplantation. Therapeutic strategies reducing the rate of graft dysfunction are of current clinical relevance. One approach is the systemic application of prostaglandins, which were demonstrated to be beneficial in reducing ischemia-reperfusion injury. Preliminary data indicate a positive effect of prostacyclin analogue iloprost on allograft viability after liver transplantation. The objective of the study is to evaluate the impact of iloprost in a multi-center trial.Methods/DesignA prospective, double-blinded, randomized, placebo-controlled multicenter study in a total of 365 liver transplant recipients was designed to assess the effect of intravenous iloprost after liver transplantation. Primary endpoint will be the primary graft dysfunction characterized as presentation of one or more of the following criteria: ALAT or ASAT level > 2000 IU/ml within the first 7 postoperative days, bilirubine ≥ 10 mg/dl on postoperative day 7; INR ≥ 1.6 on postoperative day 7 or initial non-function. Secondary endpoints are parameters of post-transplant morbidity, like rates of infections, biliary complications, need of clotting factors or renal replacement therapy and the graft and patient survival.DiscussionA well-established treatment concept to avoid graft dysfunction after liver transplantation does not exist at the moment. If the data of this research project confirm prior findings, iloprost would improve the general outcome after liver transplantation.Trial RegistrationGerman Clinical Trials Register: DRKS00003514. Current Controlled Trials Register: ISRCTN12622749.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The PRAISE study: A prospective, multi-center, randomized, double blinded, placebo-controlled study for the evaluation of iloprost in the early postoperative period after liver transplantation (ISRCTN12622749)

Barthel

Rauchfuß

Hoyer³

et al. 2013

BMC Surg

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“…Recently it has also been shown that this molecule has important roles in immune regulation (Boswell et al, 2011) and some studies suggest that treatment with PGI 2 analogs may improve early graft viability in liver transplant patients, partly by reducing levels of inflammatory cytokines (Barthel et al, 2012). …”

Section: Biosynthesis Of and Signaling By Eicosanoids In T Lymphocytesmentioning

confidence: 99%

Proinflammatory and Immunoregulatory Roles of Eicosanoids in T Cells

Lone¹,

Taskén²

2013

Front. Immunol.

109

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Eicosanoids are inflammatory mediators primarily generated by hydrolysis of membrane phospholipids by phospholipase A2 to ω-3 and ω-6 C20 fatty acids that next are converted to leukotrienes (LTs), prostaglandins (PGs), prostacyclins (PCs), and thromboxanes (TXAs). The rate-limiting and tightly regulated lipoxygenases control synthesis of LTs while the equally well-controlled cyclooxygenases 1 and 2 generate prostanoids, including PGs, PCs, and TXAs. While many of the classical signs of inflammation such as redness, swelling, pain, and heat are caused by eicosanoid species with vasoactive, pyretic, and pain-inducing effects locally, some eicosanoids also regulate T cell functions. Here, we will review eicosanoid production in T cell subsets and the inflammatory and immunoregulatory functions of LTs, PGs, PCs, and TXAs in T cells.

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“…According to previous clinical experience, doses of 0.5 to 4 ng/kg BW/minute were used for continuous infusion after liver transplant 4,9 and acute limb ischemia. 10 Because the positive effects achieved with 1 ng/kg BW/min were mild, 4 and we knew from clinical experience that a dosage of 4 ng/kg BW/minute usually was difficult to achieve because of adverse events, 9 we used 2 ng/kg BW/minute.…”

Section: Study Design and Dosementioning

confidence: 99%

“…[1][2][3][4] However, although beneficial clinically and experimentally, its use in donor pretreatment is uncommon and the exact recommendations about type of application are pending. [5][6][7] The purpose of this study was to compare 4 different iloprost treatment regimens to a control group and to determine their effect on liver injury and function after extended cold ischemia time (CIT) (20 h) in an isolated 8-hour extracorporeal pig liver perfusion model.…”

Section: Introductionmentioning

confidence: 99%

Untitled

2015

Exp Clin Transplant

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Objectives: Iloprost has the potential to protect the liver transplant graft before and during cold ischemia. We studied iloprost administration during organ procurement and reperfusion in an extracorporeal pig liver perfusion model. Materials and Methods: German Landrace pigs (n = 7/group; 22-26 kg each) were used as donors. Preservation was performed by aortic perfusion with 2L Bretschneiders' Histidine-Tryptophan-Ketoglutarate solution HTK and cold ischemia time (4°C) 20 hours followed by normothermic extracorporeal perfusion for 8 hours. Untreated controls (1) were compared to iloprost (2) donor bolus-treatment (1 μg/kg body weight), (3) addition of iloprost to Bretschneiders´ Histidine-Tryptophan-Ketoglutarate solution HTK (0.0125 μg/mL), (4) continuous infusion during reperfusion (2 ng/kg/min), and (5) combined treatment (2) and (4). Results: Iloprost donor treatment led to significantly higher bile production. Addition of iloprost to the preservation solution significantly improved hepatic artery perfusion and was accompanied by improvements of microcirculation and bile production. Iloprost reperfusion treatment alone significantly improved bile production. Enzyme levels were positively affected by all treatment regimens.Combined use of iloprost before and after ischemia improved hepatic artery flow and microcirculation and showed significantly lower hypoxia staining versus controls. Conclusions: Iloprost donor treatment and use of iloprost in the preservation solution significantly improved graft perfusion and function. The effects of graft treatment seemed greater before than after reperfusion. Combined treatment did not reveal a synergistic advantage. Key words: End-stage liver disease, Graft, Prostaglandin, Transplant IntroductionThe use of iloprost clinically and experimentally is widely accepted after liver transplant. 1-4 However, although beneficial clinically and experimentally, its use in donor pretreatment is uncommon and the exact recommendations about type of application are pending. [5][6][7] The purpose of this study was to compare 4 different iloprost treatment regimens to a control group and to determine their effect on liver injury and function after extended cold ischemia time (CIT) (20 h) in an isolated 8-hour extracorporeal pig liver perfusion model. The following parameters were assessed:• Liver perfusion (macro-and microcirculation). Materials and Methods Animals and anesthesiaGerman Landrace pigs aged 10 to 16 weeks with a mean body weight (BW) 23.7 ± 1.56 kg (range, 22-26 kg) were used as organ donors. Animals were purchased (Fa. Sommerfeld, Brandenburg, Germany) and housed in our animal facility located at Charité Campus Virchow Klinikum, Berlin, Germany, approximately 1 week before each experiment. Animals were examined after delivery and kept species-appropriate with free access to water. Twice daily they were fed with standard pig nutrition pellets (Mpig-H, Sniff Spezialitäten GmbH, Soest, Germany) and housed at a day and night cycle of 12 hours and mean temperature ...

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Impact of stable PGI₂analog iloprost on early graft viability after liver transplantation: a pilot study

Abstract: We suggest iloprost to be beneficial for early post-transplant liver function. If the rate of PDF can be significantly reduced with this treatment concept, it should be analyzed in a larger number of patients (ISRCTN95672167).

Cited by 27 publications

References 51 publications

The PRAISE study: A prospective, multi-center, randomized, double blinded, placebo-controlled study for the evaluation of iloprost in the early postoperative period after liver transplantation (ISRCTN12622749)

The PRAISE study: A prospective, multi-center, randomized, double blinded, placebo-controlled study for the evaluation of iloprost in the early postoperative period after liver transplantation (ISRCTN12622749)

Proinflammatory and Immunoregulatory Roles of Eicosanoids in T Cells

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Impact of stable PGI2analog iloprost on early graft viability after liver transplantation: a pilot study

Abstract: We suggest iloprost to be beneficial for early post-transplant liver function. If the rate of PDF can be significantly reduced with this treatment concept, it should be analyzed in a larger number of patients (ISRCTN95672167).

Cited by 27 publications

References 51 publications

The PRAISE study: A prospective, multi-center, randomized, double blinded, placebo-controlled study for the evaluation of iloprost in the early postoperative period after liver transplantation (ISRCTN12622749)

The PRAISE study: A prospective, multi-center, randomized, double blinded, placebo-controlled study for the evaluation of iloprost in the early postoperative period after liver transplantation (ISRCTN12622749)

Proinflammatory and Immunoregulatory Roles of Eicosanoids in T Cells

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Impact of stable PGI₂analog iloprost on early graft viability after liver transplantation: a pilot study