5c9a17ad2a9f3730b44aa59697d116a2 335907.pdf 976925cd7edb68c962f08a3ba49922a2723b5c40 335907.pdf 04b9cfef38e0be0b538e61d26497a237e0fb06d9584c20f05036bf3d732d62a8 335907.pdf Title: Caspase-3 in Brain Death Donors Is Associated with Reduced Primary Graft Dysfunction After Heart Transplantation Subject: Primary graft dysfunction (PGD) remains a major cause of early morbidity and mortality after a heart transplant (HTx). Understanding the donor-related mechanisms involved may help improve organ selection and post-HTx outcomes. This study aimed to explore the association between the donor serum biomarkers of cell death and inflammation and the incidence of PGD and rejection in HTx recipients. We conducted a retrospective, multicenter observational study of brain-dead (DBD) heart donors and corresponding recipients between 2013 and 2019. Donor blood samples were analyzed for inflammatory cytokines, cell death-related proteins, and mitochondrial (mtDNA) and genomic DNA (gDNA). A total of 39 donor–recipient pairs were included. Sixteen recipients developed severe PGD, and five experienced 2R cellular rejection. Donors whose recipients developed PGD had significantly lower serum Caspase-3 levels compared to those without PGD (391.6 [101.8–1003.3] vs. 65.3 [40.2–163.3] pg/mL; p = 0.04). A trend toward lower mtDNA/gDNA ratio was also observed in the same group (10.5 [5.4–24.6] vs. 6.5 [3.3–10.7]; p = 0.067). Lower Caspase-3 levels in donor serum were significantly associated with the development of severe PGD in recipients. This may suggest that the sublethal activation of apoptotic pathways in the donor could play a protective role, potentially conditioning the graft to tolerate ischemic injury. Keywords: brain death donor; primary graft disfunction; allograft rejection; inflammatory mediators; Caspase-3; cell death process; mitochondrial DNA Author: Lorena Herrador, José González-Costello, Jordi Niubo-Bosch, Laura Calatayud-Samper, Alba Maestro-Benedicto, Marta Farrero-Torres, Teresa Blasco-Peiro, Luis Almenar-Bonet, Zorba Blázquez-Bermejo, Iris Garrido-Bravo, Ferran Gran-Ipiña, Antonio Grande-Trillo, Nicolas Manito and Gabriel Moreno-Gonzalez Creator: LaTeX with hyperref Producer: MiKTeX pdfTeX-1.40.25; modified using OpenPDF 1.4.2 CreationDate: Fri Sep 26 15:18:51 2025 CEST ModDate: Fri Sep 26 15:24:52 2025 CEST Custom Metadata: yes Metadata Stream: no Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 13 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 1112371 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- IBYOVH+URWPalladioL-Bold Type 1 Custom yes yes yes 111 0 JDCKWC+CMSY10 Type 1 Builtin yes yes yes 112 0 GJLWRS+URWPalladioL-Roma Type 1 Custom yes yes yes 113 0 GSLKYZ+URWPalladioL-Ital Type 1 Custom yes yes yes 114 0 ELEZOG+EURM10 Type 1 Builtin yes yes yes 157 0 WBVKDJ+URWPalladioL-BoldItal Type 1 Custom yes yes yes 217 0 EFKANP+PalatinoLinotype,BoldItalic TrueType WinAnsi yes yes no 212 0 EFJOMH+PalatinoLinotype TrueType WinAnsi yes yes no 285 0 EFJOMF+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 286 0 EFKCIH+SimSun CID TrueType Identity-H yes yes yes 287 0 EFJOMH+PalatinoLinotype TrueType WinAnsi yes yes no 293 0 EFJOMF+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 294 0 EFKCIH+SimSun CID TrueType Identity-H yes yes yes 295 0 Jhove (Rel. 1.28.0, 2023-05-18) Date: 2026-09-10 04:10:55 CEST RepresentationInformation: 335907.pdf ReportingModule: PDF-hul, Rel. 1.12.4 (2023-03-16) LastModified: 2026-09-09 13:31:53 CEST Size: 1112371 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 404 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: ViewerPreferences: HideToolbar: false HideMenubar: false HideWindowUI: false FitWindow: true CenterWindow: false DisplayDocTitle: false NonFullScreenPageMode: UseNone Direction: L2R ViewArea: CropBox ViewClip: CropBox PrintArea: CropBox PageClip: CropBox PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Item: Title: Results Children: Item: Title: Baseline Characteristics and HTx Process Item: Title: Primary Graft Dysfunction According to Brain Death Donor Profile Item: Title: Occurrence of Rejection According to Brain Death Donor Profile Item: Title: Discussion Item: Title: Materials and Methods Children: Item: Title: Patient Selection Item: Title: Data Collection Item: Title: Sample Acquisition Item: Title: Multiplex Analysis Item: Title: Mitochondrial and Genomic DNA Item: Title: Data Analysis Item: Title: Conclusions Item: Title: Appendix A Item: Title: References Info: Title: Caspase-3 in Brain Death Donors Is Associated with Reduced Primary Graft Dysfunction After Heart Transplantation Author: Lorena Herrador, José González-Costello, Jordi Niubo-Bosch, Laura Calatayud-Samper, Alba Maestro-Benedicto, Marta Farrero-Torres, Teresa Blasco-Peiro, Luis Almenar-Bonet, Zorba Blázquez-Bermejo, Iris Garrido-Bravo, Ferran Gran-Ipiña, Antonio Grande-Trillo, Nicolas Manito and Gabriel Moreno-Gonzalez Subject: Primary graft dysfunction (PGD) remains a major cause of early morbidity and mortality after a heart transplant (HTx). Understanding the donor-related mechanisms involved may help improve organ selection and post-HTx outcomes. This study aimed to explore the association between the donor serum biomarkers of cell death and inflammation and the incidence of PGD and rejection in HTx recipients. We conducted a retrospective, multicenter observational study of brain-dead (DBD) heart donors and corresponding recipients between 2013 and 2019. Donor blood samples were analyzed for inflammatory cytokines, cell death-related proteins, and mitochondrial (mtDNA) and genomic DNA (gDNA). A total of 39 donor–recipient pairs were included. Sixteen recipients developed severe PGD, and five experienced 2R cellular rejection. Donors whose recipients developed PGD had significantly lower serum Caspase-3 levels compared to those without PGD (391.6 [101.8–1003.3] vs. 65.3 [40.2–163.3] pg/mL; p = 0.04). A trend toward lower mtDNA/gDNA ratio was also observed in the same group (10.5 [5.4–24.6] vs. 6.5 [3.3–10.7]; p = 0.067). Lower Caspase-3 levels in donor serum were significantly associated with the development of severe PGD in recipients. This may suggest that the sublethal activation of apoptotic pathways in the donor could play a protective role, potentially conditioning the graft to tolerate ischemic injury. 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