Circulating cytokine portraits can differentiate between allograft rejection and pulmonary infection in cardiac transplant rats

Chen, Hao; Li, Feng; Zhan, Yanxia; Yu, Wen-Ying; Chen, Lü; Cheng, Yunfeng; Mei, Yunqing

doi:10.1093/icvts/ivw051

Cited by 1 publication

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References 28 publications

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“…The release of such a milieu of IFN-γ associated proteins during HCP suggests a prominent role for this signaling network in mediating leukocyte migration from the heart. This is particularly true for CXCL9 which if neutralized, prevents IFN-γ secretion and is essential for donor specific T cell reactivity (14).…”

Section: Discussionmentioning

confidence: 99%

Non-ischemic Heart Preservation via Hypothermic Cardioplegic Perfusion Induces Immunodepletion of Donor Hearts Resulting in Diminished Graft Infiltration Following Transplantation

et al. 2020

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Introduction: Many donor organs contain significant leukocyte reservoirs which upon transplantation activate recipient leukocytes to initiate acute rejection. We aimed to assess whether non-ischemic heart preservation via ex vivo perfusion promotes immunodepletion and alters the inflammatory status of the donor organ prior to transplantation. Methods: Isolated porcine hearts underwent ex vivo hypothermic, cardioplegic perfusion for 8 h. Leukocyte populations were quantified in left ventricle samples by flow cytometry. Cell-free DNA, cytokines, and chemokines were quantified in the perfusate. Tissue integrity was profiled by targeted proteomics and a histological assessment was performed. Heterotopic transplants comparing ex vivo hypothermic preservation and static cold storage were utilized to assess graft infiltration as a solid clinical endpoint. Results: Ex vivo perfusion significantly immunodepleted myocardial tissue. The perfusate displayed a selective, pro-inflammatory cytokine/chemokine pattern dominated by IFN-γ. The tissue molecular profile was improved following perfusion by diminished expression of nine pro-apoptotic and six ischemia-associated proteins. Histologically, no evidence of tissue damage was observed and cardiac troponin I was low throughout perfusion. Cell-free DNA was detected, the source of which may be necrotic/apoptotic leukocytes. Post-transplant graft infiltration was markedly reduced in terms of both leucocyte distribution and intensity of foci. Conclusions: These findings demonstrate that ex vivo perfusion significantly reduced donor heart immunogenicity via loss of resident leukocytes. Despite the pro-inflammatory Critchley et al. Immunodepletion of the Donor Heart cytokine pattern observed, a pro-survival and reduced ischemia-related profile was observed, indicating an improvement in graft viability by perfusion. Diminished graft infiltration was observed in perfused hearts compared with those preserved by static cold storage following 48 h of transplantation.

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Section: Discussionmentioning

confidence: 99%

Non-ischemic Heart Preservation via Hypothermic Cardioplegic Perfusion Induces Immunodepletion of Donor Hearts Resulting in Diminished Graft Infiltration Following Transplantation

et al. 2020

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show abstract

Circulating cytokine portraits can differentiate between allograft rejection and pulmonary infection in cardiac transplant rats

Abstract: The present study demonstrated fluctuations in circulating cytokine portraits in cardiac allograft rejection and bacterial pulmonary infection after transplant. Such disease-specific cytokine patterns might facilitate early discrimination between rejection and infection.

Cited by 1 publication

References 28 publications

Non-ischemic Heart Preservation via Hypothermic Cardioplegic Perfusion Induces Immunodepletion of Donor Hearts Resulting in Diminished Graft Infiltration Following Transplantation

Non-ischemic Heart Preservation via Hypothermic Cardioplegic Perfusion Induces Immunodepletion of Donor Hearts Resulting in Diminished Graft Infiltration Following Transplantation

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