Ever since the discovery of free radicals, many hypotheses on the deleterious actions of reactive oxygen species (ROS) have been proposed. However, increasing evidence advocates the necessity of ROS for cellular homeostasis. ROS are generated as inherent by-products of aerobic metabolism and are tightly controlled by antioxidants. Conversely, when produced in excess or when antioxidants are depleted, ROS can inflict damage to lipids, proteins, and DNA. Such a state of oxidative stress is associated with many pathological conditions and closely correlated to oxygen consumption. Although the deleterious effects of ROS can potentially be reduced by restoring the imbalance between production and clearance of ROS through administration of antioxidants (AOs), the dosage and type of AOs should be tailored to the location and nature of oxidative stress. This paper describes several pathways of ROS signaling in cellular homeostasis. Further, we review the function of ROS in cardiovascular pathology and the effects of AOs on cardiovascular outcomes with emphasis on the so-called oxidative paradox.

Export Background. Heart transplantation (HTx) is, at present, the most effective therapy for end-stage heart failure patients; however, the number of patients on the waiting list is rising globally, further increasing the gap between demand and supply of donors for HTx. First studies using the Organ Care System (OCS) for normothermic machine perfusion show promising results yet are limited in sample size. This article presents a meta-analysis of heart donation either after brain death (OCS-DBD) or circulatory death (OCS-DCD) on using OCS versus static cold storage used for HTx. Methods. A systematic literature search was performed for articles discussing the use of normothermic ex situ heart perfusion in adult patients. Thirty-day survival outcomes were pooled, and odds ratios were calculated using random-effects models. Long-term survival was visualized with Kaplan-Meier curves, hazard ratios were calculated and pooled using fixed-effects models, and secondary outcomes were analyzed. Results. A total of 12 studies were included, with 741 patients undergoing HTx, of which 260 with the OCS (173 DBD and 87 DCD). No differences were found between the 3 groups for early and late survival outcomes or for secondary outcomes. Conclusions. OCS outcomes, for both DBD and DCD hearts, appeared similar as for static cold storage. Therefore, OCS is a safe and effective technique to enlarge the cardiac donor pool in both DBD and DCD, with additional benefits for long-distance transport and surgically complex procedures.

For recent decades, cardiac diseases have been the leading cause of death and morbidity worldwide. Despite significant achievements in their management, profound understanding of disease progression is limited. The lack of biologically relevant and robust preclinical disease models that truly grasp the molecular underpinnings of cardiac disease and its pathophysiology attributes to this stagnation, as well as the insufficiency of platforms that effectively explore novel therapeutic avenues. The area of fundamental and translational cardiac research has therefore gained wide interest of scientists in the clinical field, while the landscape has rapidly evolved towards an elaborate array of research modalities, characterized by diverse and distinctive traits. As a consequence, current literature lacks an intelligible and complete overview aimed at clinical scientists that focuses on selecting the optimal platform for translational research questions. In this review, we present an elaborate overview of current in vitro, ex vivo, in vivo and in silico platforms that model cardiac health and disease, delineating their main benefits and drawbacks, innovative prospects, and foremost fields of application in the scope of clinical research incentives.