Ischemia/reperfusion injury of porcine limbs after extracorporeal perfusion

Müller, Sabine; Constantinescu, Mihai A.; Kiermeir, David; Gajanayake, Thusitha; Bongoni, Anjan K.; Vollbach, Felix H.; Meoli, Martino; Plock, Jan A.; Jenni, Hansjörg; Banič, Andrej; Rieben, Robert; Vögelin, Esther

doi:10.1016/j.jss.2012.05.088

Cited by 54 publications

(47 citation statements)

References 53 publications

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“…As mentioned above, Polyak et al (2008) demonstrated that the use of a novel unoxygenated artificial solution they had developed could maintain viability of equine intestine in perfusion experiments for twelve hours and was superior to the use of whole blood (Polyak et al, 2008 expanders/replacers used for clinical and research purposes and showing a similar effect are dextran (Cameron et al, 1972;Kietzmann et al, 1993), cellulose (Friebe et al, 2013a), hydroxyethyl starch (Müller et al, 2013) and mannitol (Domingo-Pech et al, 1991;Labens et al, 2013). While mannitol is considered an inert substance, recent research has suggested possible interdependencies with monocyte and neutrophil function (upregulation of HLA-DR in monocytes, upregulation of CD11b in neutrophils and monocytes, and inhibition of neutrophil apoptosis (Turina et al, 2008)).…”

Section: Cell Free Solutionsmentioning

confidence: 97%

“…Two strategies may be applied in flow controlled experiments: a low flow or a high flow approach. In low flow circuits, the average flow rate and consequently the perfusion pressure, is below physiological values; however the flow still reaches and supplies the capillary bed, as demonstrated using dyes (Kietzmann et al, 1993), specimens remain viable for up to twelve hours (Cypel et al, 2008;Müller et al, 2013), and microvasculature impairment and hydrostatic edema formation (Cypel et al, 2008;Constantinescu et al, 2011;Müller et al, 2013) is reduced in comparison to high flow approaches. Systems which employ a high flow approach aim for physiological flow rates and perfusion pressures to mimic the in vivo situation more closely.…”

Section: Perfusatementioning

confidence: 99%

“…Perfusate reservoirs may be gassed using glassware with a sintered glass filter (Tindal, 1957), with a bubble oxygenator, which bubbles (pure) oxygen through the blood reservoir (Smith et al, 1985), or by using a rotating disc oxygenator Cameron et al, 1972), whereby several parallel discs rotate within the reservoir containing unoxygenated blood and the gas exchange occurs at the disc-blood interface. More recently, the use of membrane or hollow fiber oxygenators (Butler et al, 2002;Müller et al, 2013) typically deployed during CPB surgery or life support (extracorporeal membrane oxygenation) has been reported in perfusion experiments. These systems generally follow the same concept as rotating disc oxygenators, as oxygen exchange occurs at a porous membrane.…”

Section: Perfusatementioning

confidence: 99%

“…Hypothermic perfusions are adopted for isolated organ and limb perfusions with the aim to promote organ preservation and facilitate reimplantation (Smith et al, 1985;Domingo-Pech et al, 1991;Guarrera et al, 2004;Constantinescu et al, 2011;Müller et al, 2013). Hypothermia slows cellular metabolism and oxygen consumption, allowing lower flow rates and perfusates without specific oxygen carriers to meet metabolic requirements (Fuller and Lee, 2007).…”

Section: Temperaturementioning

confidence: 99%

“…Reported diluents have been cell free solutions (Domingo-Pech et al, 1991;Wagner et al, 2003;Erasmus et al, 2006;Friebe et al, 2013b) or autologous plasma (Patan et al, 2009;Patan-Zugaj et al, 2012, which comes with the added benefit of increasing oncotic pressure. As cell free solutions are associated with low oncotic pressure, resulting in edema formation and weight gain, adding plasma expanders such as plasma proteins (Verbeke et al, 1968;Roets et al, 1974;Patan et al, 2009) and purified albumin (Rehfeld et al, 1982;Barthel et al, 1989;Riviere et al, 1989;Brunicardi et al, 2001) perfused specimens thus reflects the degree of ischemia/reperfusion injury (Petrasek et al, 1994;Adham et al, 1997) and the integrity of the microvasculature (Müller et al, 2013). Excessive edema formation results in rapidly progressive deterioration of organ function, which renders it unsuitable for transplantation and research alike (Verbeke et al, 1972).…”

Section: Cell Free Solutionsmentioning

confidence: 99%

See 4 more Smart Citations

Extracorporeal perfusion of isolated organs of large animals – Bridging the gap between in vitro and in vivo studies

Daniel¹

2018

ALTEX

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Section: Cell Free Solutionsmentioning

confidence: 97%

Section: Perfusatementioning

confidence: 99%

Section: Perfusatementioning

confidence: 99%

Section: Temperaturementioning

confidence: 99%

Section: Cell Free Solutionsmentioning

confidence: 99%

See 3 more Smart Citations

Extracorporeal perfusion of isolated organs of large animals – Bridging the gap between in vitro and in vivo studies

Daniel¹

2018

ALTEX

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Randomized preclinical study of machine perfusion in vascularized composite allografts

Amin

Stone²,

Kerr³

et al. 2021

British Journal of Surgery

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Background Attempts to improve limb preservation for transplantation using ex vivo perfusion have yielded promising results. However, metabolic acidosis, aberrant perfusate biochemistry and significant perfusion-induced oedema are reported universally. Optimizing perfusion protocols is therefore essential for maintaining tissue health. Methods A randomized, two-stage open preclinical trial design was used to determine the optimal temperature and mean arterial pressure for machine perfusion. Conditions compared were: normothermic machine perfusion at 70 mmHg (NMP-70); subnormothermic perfusion (28°C) at 70 mmHg; subnormothermic (28°C) perfusion at 50 mmHg; and hypothermic perfusion (10°C) at 30 mmHg. Following this, a head-to-head experiment was undertaken comparing the optimal machine perfusion with static cold storage. Paired bilateral limbs (10 in total) were randomized to either 8 h of static cold storage, or 2 h of static cold storage and 6 h of optimal machine perfusion. Both groups of limbs were then reperfused on a circuit primed with matched blood from unrelated donors for 4 h without immunosuppression. Results NMP-70 resulted in less tissue injury and stable perfusion biochemistry. Assessing reperfusion outcomes, static cold storage resulted in acidosis with increased lactate and a worsening electrolyte profile, necessitating bolus infusions of bicarbonate to prevent graft loss. Conversely, NMP-70 was associated with haemodynamic and biochemical stability. Histologically, on reperfusion with allogeneic whole blood, limbs subjected to static cold storage exhibited multifocal ischaemic injury and increased inflammation, which was absent with NMP-70. Static cold storage also resulted in significant oedema compared with NMP-70. Conclusion Normothermic perfusion resulted in superior graft preservation and less reperfusion injury compared with the current static cold storage protocol.

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Development of a bead‐based multiplex assay for the simultaneous detection of porcine inflammation markers using xMAP technology

et al. 2013

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Commercially available assays for the simultaneous detection of multiple inflammatory and cardiac markers in porcine blood samples are currently lacking. Therefore, this study was aimed at developing a bead-based, multiplexed flow cytometric assay to simultaneously detect porcine cytokines [interleukin (IL)-1b, IL-6, IL-10, and tumor necrosis factor alpha], chemokines (IL-8 and monocyte chemotactic protein 1), growth factors [basic fibroblast growth factor (bFGF), vascular endothelial growth factor, and platelet-derived growth factor-bb], and injury markers (cardiac troponin-I) as well as complement activation markers (C5a and sC5b-9). The method was based on the Luminex xMAP technology, resulting in the assembly of a 6-and 11-plex from the respective individual singleplex situation. The assay was evaluated for dynamic range, sensitivity, cross-reactivity, intra-assay and interassay variance, spike recovery, and correlation between multiplex and commercially available enzyme-linked immunosorbent assay as well as the respective singleplex. The limit of detection ranged from 2.5 to 30,000 pg/ml for all analytes (6-and 11-plex assays), except for soluble C5b-9 with a detection range of 2-10,000 ng/ml (11-plex). Typically, very low cross-reactivity (\3% and \1.4% by 11-and 6-plex, respectively) between analytes was found. Intra-assay variances ranged from 4.9 to 7.4% (6-plex) and 5.3 to 12.9% (11-plex). Interassay variances for cytokines were between 8.1 and 28.8% (6-plex) and 10.1 and 26.4% (11-plex). Correlation coefficients with singleplex assays for 6-plex as well as for 11-plex were high, ranging from 0.988 to 0.997 and 0.913 to 0.999, respectively. In this study, a bead-based porcine 11-plex and 6-plex assay with a good assay sensitivity, broad dynamic range, and low intra-assay variance and cross-reactivity was established. These assays therefore represent a new, useful tool for the analysis of samples generated from experiments with pigs. ' 2013 International Society for Advancement of Cytometry

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Ischemia/reperfusion injury of porcine limbs after extracorporeal perfusion

Cited by 54 publications

References 53 publications

Extracorporeal perfusion of isolated organs of large animals – Bridging the gap between in vitro and in vivo studies

Extracorporeal perfusion of isolated organs of large animals – Bridging the gap between in vitro and in vivo studies

Randomized preclinical study of machine perfusion in vascularized composite allografts

Development of a bead‐based multiplex assay for the simultaneous detection of porcine inflammation markers using xMAP technology

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