Purpose: Inhaled nitric oxide (iNO) has been shown to reduce ischemiareperfusion injury (IRI) by several putative mechanisms.In preclinical lung transplantation studies it has been shown to reduce acute rejections.In heart transplantation (HTx), iNO is routinely used to decrease pulmonary vascular resistance.However, iNO treatment's effect on later outcomes after HTx remains unknown.Methods: We analyzed retrospectively clinical data and plasma samples of 84 donor-recipient pairs of a prospective single-center trial collected between 2010-2016.Recipient plasma was collected 1, 6, 12, and 24h after transplantation.Routine laboratory parameters such as TnT, TnI, CKMBm, and proBNP were measured as biomarkers for early graft injury and function.Endomyocardial biopsies were taken at routine timepoints after HTx and during suspected rejection.Follow-up was conducted until five years after HTx.Results: Of the 84 patients, 58.3% received iNO.Preoperatively, iNO-recipients had higher bilirubin and proBNP, and a trend for higher transpulmonary pressure (P=0.058).Postoperatively, iNO-recipients had higher TnT, TnI, and proBNP plasma levels (P<0.01-0.05),and an increased need for renal replacement therapy (P<0.001) compared to patients not receiving iNO.iNO-recipients were more likely to receive antithymocyte globulin (ATG) and tacrolimus as their postoperative immunosuppressive medication.In 5-year follow-up, mortality between groups was similar.After adjusting for differences in immunosuppressive medication between groups, iNO-recipients had lower incidence of acute rejection of any grade (71% vs 91%) and a trend for fewer severe acute rejections (grades 2-3; 27% vs 34%).Furthermore, iNO-recipients had a trend for less chronic allograft vasculopathy of any grade in 5-year follow-up (36% vs 64%, P=0.069).Conclusion: iNO-recipients were sicker preoperatively and had worse IRI after transplantation.However, in long-term follow-up, iNO-treatment associated with less rejections even after adjusting for differences in immunosuppressive medication.Our findings suggest that iNO may have cardioprotective effects after HTx.In ISHLT 2023 meeting we aim to present mechanistic insight on these findings by studying the effect of iNO on plasma proteomics after HTx.
metabolizing both glucose and lactate.The hearts that were transplanted displayed stable hemodynamics and good biventricular function.Conclusion: Neonatal and pediatric hearts can be safely perfused for an extended period of time at subnormothermic conditions in a blood-based perfusate.This approach could significantly enhance donor organ sharing by removing geographical and transportation barriers.Further work is required to determine the optimal perfusate composition and metabolic support.