Hemoglobin-Based Oxygen Carriers: Potential Applications in Solid Organ Preservation

Ameliorating graft injury induced by ischemia and hypoxia, expanding the donor pool, and improving graft quality and recipient prognosis are still goals pursued by the transplant community. The preservation of organs during this process from donor to recipient is critical to the prognosis of both the graft and the recipient. At present, static cold storage, which is most widely used in clinical practice, not only reduces cell metabolism and oxygen demand through low temperature but also prevents cell edema and resists apoptosis through the application of traditional preservation solutions, but these do not improve hypoxia and increase oxygenation of the donor organ. In recent years, improving the ischemia and hypoxia of grafts during preservation and repairing the quality of marginal donor organs have been of great concern. Hemoglobin-based oxygen carriers (HBOCs) are “made of” natural hemoglobins that were originally developed as blood substitutes but have been extended to a variety of hypoxic clinical situations due to their ability to release oxygen. Compared with traditional preservation protocols, the addition of HBOCs to traditional preservation protocols provides more oxygen to organs to meet their energy metabolic needs, prolong preservation time, reduce ischemia–reperfusion injury to grafts, improve graft quality, and even increase the number of transplantable donors. The focus of the present study was to review the potential applications of HBOCs in solid organ preservation and provide new approaches to understanding the mechanism of the promising strategies for organ preservation.

Heparanase inhibition preserves the endothelial glycocalyx in lung grafts and improves lung preservation and transplant outcomes

The endothelial glycocalyx (eGC) is considered a key regulator of several mechanisms that prevent vascular injury and disease. Degradation of this macromolecular layer may be associated with post-transplant graft dysfunction. In this study, we aimed to demonstrate the benefits of eGC protection via heparanase inhibition on graft quality. We established rat models of lung grafts with damaged or preserved eGC using ischemic insult and transplanted the grafts into recipients. Lung grafts were also subjected to normothermic ex vivo lung perfusion for detailed assessment under isolated conditions. Physiologic parameters and eGC-associated cellular events were assessed in grafts before and after reperfusion. Structurally degraded eGC and highly activated heparanase were confirmed in lungs with ischemic insult. After transplant, lungs with damaged eGC exhibited impaired graft function, inflammation, edema, and inflammatory cell migration. Increased eGC shedding was evident in the lungs after reperfusion both in vivo and ex vivo. These reperfusion-related deficiencies were significantly attenuated in lungs with preserved eGC following heparanase inhibition. Our studies demonstrated that eGC plays a key role in maintaining lung graft quality and function. Heparanase inhibition may serve as a potential therapeutic to preserve eGC integrity, leading to improved post-transplant outcomes.

In patients undergoing coronary artery bypass grafting, is endoscopic harvesting superior to open radial artery harvesting?

Summary A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was ‘In patients undergoing coronary artery bypass grafting, is endoscopic radial artery harvesting (ERAH) superior to open radial artery harvesting in terms of postoperative complications, mortality, graft quality and patency rates?’. Altogether 130 papers were found using the reported search, of which 5 represented the best evidence to answer the clinical question. Two studies were meta-analyses and 3 were randomized trials. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. In terms of graft quality, 2 randomized studies showed preserved endothelial integrity and vasoreactivity with ERAH, whereas 1 randomized study found superior endothelial function with open radial artery harvesting. Importantly, 3 studies showed graft patency was not compromised with ERAH. One meta-analysis reported no differences in graft patency between groups at 1 year [odds ratio (OR) 1.24] and up to 3–5-years follow-up (OR 1.81), as well as similar perioperative myocardial infarction rates (OR 0.80). Two meta-analyses found similar mortality in the perioperative period (OR 0.62–0.78) and up to 5 years (OR 0.64–0.67); ERAH reduced the incidence of perioperative wound complications (P-values 0.001–0.03); however, harvest times were increased with ERAH (P < 0.0005). We conclude that ERAH is non-inferior to open radial artery harvesting in terms of mortality, graft quality and patency rates, but superior in terms of reducing perioperative wound complications, with good cosmetic effect. However, these benefits come at the cost of increased harvesting time.