Oxygen saturation in intraosseous sternal blood measured by CO-oximetry and evaluated non-invasively during hypovolaemia and hypoxia – a porcine experimental study

Näslund, Erik; Lindberg, Lars‐Göran; Strandberg, Gunnar; Apelthun, Catharina; Franzén, Stephanie; Frithiof, Robert

doi:10.1007/s10877-023-00980-z

Cited by 1 publication

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“…SvO2 has been suggested to be a clinically reliable indicator of an appropriated oxygen supply. Both in pigs and humans, SvO2 usually varies between 65 and 85% ( 26 ). This left-LTx model complicates the assessment of physiological parameters related to graft function, such as SvO2, because of the functionality of the recipient’s own lung.…”

Section: Discussionmentioning

confidence: 99%

Knockdown of swine leukocyte antigen expression in porcine lung transplants enables graft survival without immunosuppression

Figueiredo,

Chen-Wacker,

Salman

et al. 2024

Sci. Transl. Med.

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Immune rejection remains the major obstacle to long-term survival of allogeneic lung transplants. The expression of major histocompatibility complex molecules and minor histocompatibility antigens triggers allogeneic immune responses that can lead to allograft rejection. Transplant outcomes therefore depend on long-term immunosuppression, which is associated with severe side effects. To address this problem, we investigated the effect of genetically engineered transplants with permanently down-regulated swine leukocyte antigen (SLA) expression to prevent rejection in a porcine allogeneic lung transplantation (LTx) model. Minipig donor lungs with unmodified SLA expression (control group, n = 7) or with modified SLA expression (treatment group, n = 7) were used to evaluate the effects of SLA knockdown on allograft survival and on the nature and strength of immune responses after terminating an initial 4-week period of immunosuppression after LTx. Genetic engineering to down-regulate SLA expression was achieved during ex vivo lung perfusion by lentiviral transduction of short hairpin RNAs targeting mRNAs encoding β2-microglobulin and class II transactivator. Whereas all grafts in the control group were rejected within 3 months, five of seven animals in the treatment group maintained graft survival without immunosuppression during the 2-year monitoring period. Compared with controls, SLA-silenced lung recipients had lower donor-specific antibodies and proinflammatory cytokine concentrations in the serum. Together, these data demonstrate a survival benefit of SLA–down-regulated lung transplants in the absence of immunosuppression.

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Section: Discussionmentioning

confidence: 99%