Erythropoietin inhibits post-ischemic leukocyte adhesion but does not affect rejection in murine cardiac allografts

Schramm, René; Kirsch, Sarah; Schäfers, Hans‐Joachim; Langer, Frank; Scheuer, Cláudia; Nickels, Ruth M.; Harder, Yves; Menger, Michael D.

doi:10.1016/j.healun.2010.05.035

Cited by 6 publications

(12 citation statements)

References 43 publications

(45 reference statements)

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“…The finding of platelet-endothelial cell interactions in postcapillary coronary venules suggests a novel mechanistic aspect in xenogeneic graft destruction, as it has been widely accepted that thromboembolic occlusion of the arteriolar bloodstream leads to infarction and tissue destruction. This is obviously different to allogeneic cardiac rejection, during which such platelet interactions were not observed [19] .…”

Section: Discussionmentioning

confidence: 84%

“…The detection of reactive hyperaemia validates our experimental protocol for future IVM assessments of the xenografts' microcirculation addressing dynamic vasoreactivity changes during later reperfusion phases. In fact, prolonged reperfusion injury and the no-reflow phenomenon may hamper later adequate graft perfusion, as it has been observed in experimental cardiac allografts [19] .…”

Section: Discussionmentioning

confidence: 96%

“…For the first time, we herein used IVM to visualise microcirculatory dysfunction and inflammation directly in the subepicardial microvasculature of transplanted cardiac xenografts. The principle technique has already been proven to be a very valid approach to monitor ischaemia/reperfusion injury and rejection in allogeneic experimental transplantation [12,19,20] .…”

Section: Discussionmentioning

confidence: 99%

“…This offers an easily applicable transplantation model with excellent access to the transplanted graft for IVM [12,19,21] . Blood results of hamster-to-rat cardiac xenotransplantation in group 1 after 90 min IVM, in group 2 after long-term survival and in group 3 after sensitisation.…”

Section: Discussionmentioning

confidence: 99%

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The coronary microcirculation in hamster-to-rat cardiac xenografts

Buchholz¹,

Geiger²,

Michel³

et al. 2013

Thorac cardiovasc Surg

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Background:The aim of this study was to establish a new experimental model to directly analyse the coronary microcirculation in cardiac xenografts. Methods: Intravital fluorescence microscopy (IVM) of the subepicardial microcirculation in heterotopically transplanted hamster-to-rat cardiac xenografts was performed at 30 and 90 min of reperfusion. We quantitatively assessed the microcirculatory perfusion characteristics as well as the interactions of leukocytes and platelets with the endothelium of postcapillary coronary venules in non-sensitised as well as sensitised recipients. Results: In this first experimental IVM study of cardiac xenografts, we successfully visualised the subepicardial microcirculation, i.e. feeding arterioles, nutritive capillaries and draining postcapillary venules, during reperfusion. Leukocyteendothelial and platelet-endothelial cell interactions could be quantified. In the non-sensitised group, the myocardial microcirculation remained stable during the observation period of 90 min, whereas in the sensitised group, xenografts were rejected immediately. Conclusions: We established a model for the assessment of the microcirculatory dysfunction and inflammation during ischaemia/reperfusion injury in hamster-to-rat cardiac xenografts.

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Section: Discussionmentioning

confidence: 84%

Section: Discussionmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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The coronary microcirculation in hamster-to-rat cardiac xenografts

Buchholz¹,

Geiger²,

Michel³

et al. 2013

Thorac cardiovasc Surg

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“…We also postulate that erythropoietin (EPO) may provide a therapeutic benefit in ARDS due to its anti-inflammatory properties, its ability to positively modulate immune responses [18,19] and influence cell apoptosis [20,21,22]. Upregulation of anti-apoptotic genes, such as Janus tyrosine kinase-2, STAT5 (signal transducer and activator of transcription 5), Bcl-2, phosphatidylinositol 3, protein kinase B, mitogen-activated protein kinase and nuclear factor-κB (NFκB), after systemic EPO administration for 14 days has been described, and no immediate negative side effects were clinically observed [23].…”

Section: Introductionmentioning

confidence: 99%

Autologous Peripheral Blood Mononuclear Cells as Treatment in Refractory Acute Respiratory Distress Syndrome

Jungebluth

Holzgraefe²,

Lim³

et al. 2015

Respiration

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Background: Acute respiratory distress syndrome (ARDS) is a devastating disorder. Despite enormous efforts in clinical research, effective treatment options are lacking, and mortality rates remain unacceptably high. Objectives: A male patient with severe ARDS showed no clinical improvement with conventional therapies. Hence, an emergent experimental intervention was performed. Methods: We performed intratracheal administration of autologous peripheral blood-derived mononuclear cells (PBMCs) and erythropoietin (EPO). Results: We found that after 2 days of initial PBMC/EPO application, lung function improved and extracorporeal membrane oxygenation (ECMO) support was reduced. Bronchoscopy and serum inflammatory markers revealed reduced inflammation. Additionally, serum concentration of miR-449a, b, c and miR-34a, a transient upregulation of E-cadherin and associated chromatin marks in PBMCs indicated airway epithelial differentiation. Extracellular vesicles from PBMCs demonstrated anti-inflammatory capacity in a TNF-a-mediated nuclear factor-κB in vitro assay. Despite improving respiratory function, the patient died of multisystem organ failure on day 38 of ECMO treatment. Conclusions: This case report provides initial encouraging evidence to use locally instilled PBMC/EPO for treatment of severe refractory ARDS. The observed clinical improvement may partially be due to the anti-inflammatory effects of PBMC/EPO to promote tissue regeneration. Further studies are needed for more in-depth understanding of the underlying mechanisms of in vivo regeneration.

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