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The ischemia–reperfusion process of a donor heart during heart transplantation leads to severe mitochondrial dysfunction, which may be the main cause of donor heart dysfunction after heart transplantation. Pyruvate carboxylase (PC), an enzyme found in mitochondria, is said to play a role in the control of oxidative stress and the function of mitochondria. This research examined the function of PC and discovered the signaling pathways controlled by PC in myocardial IRI. We induced IRI using a murine heterotopic heart transplantation model in vivo and a hypoxia–reoxygenation cell model in vitro and evaluated inflammatory responses, oxidative stress levels, mitochondrial function, and cardiomyocyte apoptosis. In both in vivo and in vitro settings, we observed a significant decrease in PC expression during myocardial IRI. PC knockdown aggravated IRI by increasing MDA content, LDH activity, TUNEL-positive cells, serum cTnI level, Bax protein expression, and the level of inflammatory cytokines and decreasing SOD activity, GPX activity, and Bcl-2 protein expression. PC overexpression yielded the opposite findings. Additional research indicated that reducing PC levels could block the Wnt/β-catenin pathway and glutamine metabolism by hindering the movement of β-catenin to the nucleus and reducing the activity of complex I and complex II, as well as ATP levels, while elevating the ratios of NADP+/NADPH and GSSG/GSH. Overall, the findings indicated that PC therapy can shield the heart from IRI during heart transplantation by regulating glutamine metabolism through the Wnt/β-catenin pathway. [ABSTRACT FROM AUTHOR]

Aims Circadian clocks play important role in immunoregulation. We aimed to investigate cardiac circadian clock specific pathways and compare cardiac grafts procured at different timing on survival after transplantation to explore novel criteria for donor selection. Methods and results In primate heart, phase set enrichment analysis (PSEA) showed rhythmic transcripts were enriched in antigen processing and presentation during activation of circadian rhythm. Digital sorting of immune cell composition and single-sample gene set enrichment analysis (ssGSEA) in unused donor transcriptomes showed the pathway, positive regulation of circadian rhythm significantly correlates with allograft rejection and antigen presentation pathways as well as with increased compositions of matured dendritic cell, CD4+ T cell, and naive B cell. Single-centre retrospective cohort of 390 adult heart transplants between 1 January 2015 and 31 December 2020 was used to generate a propensity score matching (PSM) cohort. Survival curve differed significantly showing inferior long-term survival when donor hearts were procured at activation group (12 pm to 12 am) compared to repression group (12 am to 12 pm) (6-year survival: 64.2% vs. 75.8%, P = 0.0065). Activation group was also associated with significantly higher rates of in-hospital death, cardiopulmonary resuscitation, and usage of mechanical circulatory support after heart transplantation compared to repression group. Furthermore, tendency for post-transplant free of rejection rates was higher in repression group compared to activation group (acute rejection, Gehan–Breslow P = 0.11 and 0.04; chronic rejection, Log rank P = 0.077 and 0.15, in full and PSM cohorts, respectively). Adjusted Cox regression analysis showed that activation group was associated with 2.20 times increased hazard of death (hazard ratio: 2.20; 95% confidence interval: 1.23–3.95; P = 0.008) compared to repression group. Conclusions Circadian immunity may represent donor-related risk factors for cardiac allograft rejection through activating genes related to antigen presentation pathway and immune cells oscillation at specific time of day. Molecular circadian clock should be considered during retrieval of cardiac allografts in order to maximize graft durability. [ABSTRACT FROM AUTHOR]

Background: Heart transplantation is the definitive therapy for patients with end‐stage heart failure. Antecedent studies reported that a substantial proportion of heart transplant recipients developed postoperative cognitive impairment in the long term. However, no studies have explored the association between postoperative cognitive impairment and survival after heart transplantation. Methods: The data of 43 adult patients who underwent heart transplantation were consecutively enrolled and assessed using the MMSE and MoCA neuropsychological tests. Kaplan‐Meier curves and Cox proportional hazards models were used for survival analyses. Primary component analysis was performed to integrate MoCA subtests into the "Attention factor," "Naming factor," and "Orientation factor." Results: About 30% of the patients were diagnosed with short‐term postoperative cognitive impairment. The impairment group was older and had lower baseline cognitive performances, larger LV diameter, worse MMSE decline and higher ratio of significant MoCA decline. Postoperative cognitive impairment was significantly associated with worse survival (P =.028). Multivariate Cox analyses showed that higher postoperative MoCA score was significantly associated with lower mid‐term post‐transplant mortality (HR =.744 [.584,.949], P =.017), in which "Attention factor" contributed to this association most (HR =.345 [.123,.970], P =.044) rather than "Naming factor" or "Orientation factor." Notably, preoperative cognitive impairment was closely related with postoperative cognitive impairment and also indicated the worse post‐transplant survival (P =.015). Conclusion: Postoperative as well as preoperative cognitive impairments were associated with a worse mid‐term survival after heart transplantation, indicating that neuropsychological assessments before and after heart transplantation should be routinely performed for heart transplant recipients for better risk stratification. [ABSTRACT FROM AUTHOR]

Background: In the early postoperative stage after heart transplantation, there is a lack of predictive tools to guide postoperative management. Whether the vasoactive-inotropic score (VIS) can aid this prediction is not well illustrated., Methods: In total, 325 adult patients who underwent heart transplantation at our center between January 2015 and December 2018 were included. The maximum VIS (VIS max ) within 24 h postoperatively was calculated. The Kaplan-Meier method was used for survival analysis. A logistic regression model was established to determine independent risk factors and to develop a nomogram for a composite severe adverse outcome combining early mortality and morbidity., Results: VIS max was significantly associated with extensive early outcomes such as early death, renal injury, cardiac reoperation and mechanical circulatory support in a grade-dependent manner, and also predicted 90-day and 1-year survival ( p < 0.05). A VIS-based nomogram for the severe adverse outcome was developed that included VIS max , preoperative advanced heart failure treatment, hemoglobin and serum creatinine. The nomogram was well calibrated (Hosmer-Lemeshow p = 0.424) with moderate to strong discrimination (C-index = 0.745) and good clinical utility., Conclusion: VIS max is a valuable prognostic index in heart transplantation. In the early post-transplant stage, this VIS-based nomogram can easily aid intensive care clinicians in inferring recipient status and guiding postoperative management., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Xiong, Yim, Chi, Wang, Lan, Zhang, Sun, Shi, Chen and Dong.)