The global shortage of donor hearts available for transplantation is a major problem for the treatment of end-stage heart failure. The ischemic time for donor hearts using traditional preservation by standard static cold storage (SCS) is limited to approximately 4 hours, beyond which the risk for primary graft dysfunction (PGD) significantly increases. Hypothermic machine perfusion (HMP) of donor hearts has been proposed to safely extend ischemic time without increasing the risk of PGD. Using our sheep model of 24 hours brain death (BD) followed by orthotopic heart transplantation (HTx), we examined post-transplant outcomes in recipients following donor heart preservation by HMP for 8 hours, compared to donor heart preservation for 2 hours by either SCS or HMP. Following HTx, all HMP recipients (both 2 hours and 8 hours groups) survived to the end of the study (6 hours after transplantation and successful weaning from cardiopulmonary bypass), required less vasoactive support for hemodynamic stability, and exhibited superior metabolic, fluid status and inflammatory profiles compared to SCS recipients. Contractile function and cardiac damage (troponin I release and histological assessment) was comparable between groups. Overall, compared to current clinical SCS, recipient outcomes following transplantation are not adversely impacted by extending HMP to 8 hours. These results have important implications for clinical transplantation where longer ischemic times may be required (e.g., complex surgical cases, transport across long distances). Additionally, HMP may allow safe preservation of "marginal" donor hearts that are more susceptible to myocardial injury and facilitate increased utilization of these hearts for transplantation.

Background: Evaluation of donor lung function relies on the arterial oxygen partial pressure to inspired oxygen fraction ratio (PaO ₂ /FiO ₂ ) measurement. Hemodynamic, metabolic derangements, and therapeutic intervention occurring during brain dead observation may influence the evaluation of gas exchange. Methods: We performed a mathematical analysis to explore the influence of the extrapulmonary determinants on the interpretation of PaO ₂ /FiO ₂ in the brain‐dead donor and during Ex‐Vivo Lung Perfusion (EVLP). Results: High FiO ₂ and increased mixed venous oxygen saturation, caused by increased delivery and reduced consumption of oxygen, raise the PaO ₂ /FiO ₂ despite substantial intrapulmonary shunt. Anemia does not modify the PaO ₂ /FiO ₂ —intrapulmonary shunt relationship. During EVLP, the reduced artero‐venous difference in oxygen content increases the PaO ₂ /FiO ₂ without this corresponding to an optimal graft function, while the reduced perfusate oxygen‐carrying capacity linearizes the PaO ₂ /FiO ₂ —intrapulmonary shunt relationship. Conclusions: Adopting PaO ₂ /FiO ₂ to evaluate graft suitability for transplantation should account for extrapulmonary factors affecting its interpretation.

Objectives: Extracorporeal respiratory support, including low blood flow systems providing mainly extracorporeal CO₂ removal, are increasingly applied in clinical practice. Gas exchange physiology during extracorporeal respiratory support is complex and differs between full extracorporeal membrane oxygenation and extracorporeal CO₂ removal. Aim of the present article is to review pathophysiological aspects which are relevant for the understanding of hypoxemia development during extracorporeal CO₂ removal. We will describe the mathematical and physiologic background underlying changes in respiratory quotient and alveolar oxygen tension during venovenous extracorporeal gas exchange and highlight the clinical implications. Design: Theoretical analysis of venovenous extracorporeal gas exchange. Setting: Italian university research hospital. Patients: None. Interventions: None. Measurements and Main Results: While the effect of extracorporeal CO₂ removal on the respiratory quotient of the native lung has long been known, the role of extracorporeal oxygenation in dictating changes in the respiratory quotient has been less addressed. Indeed, both extracorporeal CO₂ removal and extracorporeal oxygen delivery affect the respiratory quotient of the native lung and thus influence the alveolar Po ₂. Indeed, for the same amount of extracorporeal CO₂ extraction, it is possible to reduce the Fio ₂, reduce the risk of absorption atelectasis, and maintain the same alveolar Po ₂, by increasing the extracorporeal oxygen delivery. Conclusions: Worsening of hypoxemia is frequent during low-flow extracorporeal CO₂ removal combined with ultraprotective mechanical ventilation. In this context, increasing extracorporeal oxygen delivery, increases the respiratory quotient of the native lung and could reduce both the occurrence of alveolar hypoxia and absorption atelectasis, thus optimizing the residual lung function.

Veno-venous extracorporeal membrane oxygenation (vv-ECMO) represents one of the most advanced respiratory support for patients suffering from severe acute respiratory distress syndrome. During vv-ECMO a certain amount of extracorporeal oxygenated blood can flow back from the reinfusion into the drainage cannula without delivering oxygen to the patient. Detection and quantification of this dynamic phenomenon, defined recirculation, are critical to optimize the ECMO efficiency. Our study aimed to measure the recirculation fraction (RF) using a thermodilution technique. We built an in vitro circuit to simulate patients undergoing vv-ECMO (ECMO flow: 1.5, 3, and 4.5 L/min) with different cardiac output, using a recirculation bridge to achieve several known RFs (from 0% to 50%). The RF, computed as the ratio of the area under temperature-time curves (AUC) of the drainage and reinfusion, was significantly related to the set RF (AUC ratio (%) = 0.979 × RF (%) + 0.277%, p < 0.0001), but it was not dependent on tested ECMO and cardiac output values. A Bland–Altman analysis showed an AUC ratio bias (precision) of −0.21% for the overall data. Test-retest reliability showed an intraclass correlation coefficient of 0.993. This study proved the technical feasibility and computation validity of the applied thermodilution technique in computing vv-ECMO RF.