Cardiac Graft Assessment in the Era of Machine Perfusion: Current and Future Biomarkers

Heart transplantation remains the treatment of reference for patients experiencing end‐stage heart failure; unfortunately, graft availability through conventional donation after brain death is insufficient to meet the demand. Use of extended‐criteria donors or donation after circulatory death has emerged to increase organ availability; however, clinical protocols require optimization to limit or prevent damage in hearts possessing greater susceptibility to injury than conventional grafts. The emergence of cardiac ex situ machine perfusion not only facilitates the use of extended‐criteria donor and donation after circulatory death hearts through the avoidance of potentially damaging ischemia during graft storage and transport, it also opens the door to multiple opportunities for more sensitive monitoring of graft quality. With this review, we aim to bring together the current knowledge of biomarkers that hold particular promise for cardiac graft evaluation to improve precision and reliability in the identification of hearts for transplantation, thereby facilitating the safe increase in graft availability. Information about the utility of potential biomarkers was categorized into 5 themes: (1) functional, (2) metabolic, (3) hormone/prohormone, (4) cellular damage/death, and (5) inflammatory markers. Several promising biomarkers are identified, and recommendations for potential improvements to current clinical protocols are provided.

Comparison of Experimental Rat Models in Donation After Circulatory Death (DCD): in-situ vs. ex-situ Ischemia

Introduction: Donation after circulatory death (DCD) could substantially improve donor heart availability. However, warm ischemia prior to procurement is of particular concern for cardiac graft quality. We describe a rat model of DCD with in-situ ischemia in order to characterize the physiologic changes during the withdrawal period before graft procurement, to determine effects of cardioplegic graft storage, and to evaluate the post-ischemic cardiac recovery in comparison with an established ex-situ ischemia model.Methods: Following general anesthesia in male, Wistar rats (404 ± 24 g, n = 25), withdrawal of life-sustaining therapy was simulated by diaphragm transection. Hearts underwent no ischemia or 27 min in-situ ischemia and were explanted. Ex situ, hearts were subjected to a cardioplegic flush and 15 min cold storage or not, and 60 min reperfusion. Cardiac recovery was determined and compared to published results of an entirely ex-situ ischemia model (n = 18).Results: In donors, hearts were subjected to hypoxia and hemodynamic changes, as well as increased levels of circulating catecholamines and free fatty acids prior to circulatory arrest. Post-ischemic contractile recovery was significantly lower in the in-situ ischemia model compared to the ex-situ model, and the addition of cardioplegic storage improved developed pressure-heart rate product, but not cardiac output.Conclusion: The in-situ model provides insight into conditions to which the heart is exposed before procurement. Compared to an entirely ex-situ ischemia model, hearts of the in-situ model demonstrated a lower post-ischemic functional recovery, potentially due to systemic changes prior to ischemia, which are partially abrogated by cardioplegic graft storage.

Storage solutions for vein grafts

Even though total arterial revascularization is increasingly used, saphenous vein grafts are still the most commonly used conduits for coronary arterial bypass grafting worldwide. Every surgeon should keep in mind that a vascular graft is living tissue with active metabolism, analogous to a solid organ for transplant, and should understand the impact of the choice of the storage solution. Unfortunately, the choice of the storage solution is usually not the result of a thoughtful review of alternatives and evidence but is a function of habit, convenience, and availability. The ideal storage solution should preserve and restore endothelial functional after harvesting. Much effort has been invested in finding ways to avoid or prevent endothelial lesions during harvesting and storage, as well as delaying vein graft dilatation after coronary arterial bypass grafting. After a brief reminder of the vein graft failure pathophysiology, this chapter discusses storage conditions using the existing graft storage solutions and their influence on endothelial function and graft patency. The use of external stenting for vein grafts is addressed elsewhere.

Comparison of Bone Graft Storage Effectiveness Between Cryopreservation and Subcutaneous in Patients Conducted Craniectomy Decompression

Decompression craniectomy is a surgical method used for immediate reduction of intracranial pressure. Repair of cranial bone defects to protect the brain and reconstruct the original cranial brain compartment is called a cranioplasty. In this study researchers will conduct research and compare storage of bone graft in the freezer with a temperature of -20 ° C and subcutaneous to the risk of infection. The research design used was paired clinical trials. Clinical tests were in open label form. The analysis of significance using the Mann Whitnay test showed that the value of p = 0.381. This means that there is no significant difference between the storage group in the subcutie and the storage group in the Cryopreservation (p> 0.05). The analysis of significance using the McNemar test showed that the p value = 0.003. This means that there is a significant relationship between the storage group in the subcutie and the storage group in the Cryopreservation (p <0.05).

The Effect of Modified Biolasol Solution on the Efficacy of Storing Isolated Porcine Kidneys

Biolasol is a newly developed solution for storing the liver, pancreas, kidneys, and heart by simple hypothermia. It exhibits high efficacy in maintaining structural and functional integrity of the graft prior to its transplantation. The solution was modified by the addition of ascorbic acid (0.088g/l) and ascorbic acid with prolactin (1 μg/l PRL + 0.088g/l vitamin C). The effectiveness of the obtained solutions in the protection of nephrons of isolated porcine kidneys was assessed based on the analysis of the activity of ALT (alanine aminotransferase), AST (aspartate aminotransferase), and LDH (lactate dehydrogenase) as well as lactate concentration determined in perfundates collected after 2 h (0′ and 30′ preservation) and 48 h (0′ and 30′ preservation) of graft storage. It has been found that the synergistic action of Biolasol components determines the integrity and stability of cell membranes, which in turn affects the proper functioning of the organ after transplantation. The addition of ascorbic acid and prolactin to Biolasol affects the maintenance of the normal cytoskeleton of the stored graft.

Tips for optimizing organ preservation solutions

Organ injury during ischemia is one of the clinical problems of today's transplantation. It occurs during warm ischemia time (WIT) when the blood flow is cut off and during cold ischemia when a graft is chilled in situ until the circulation is restored to the recipient organism. Fast cooling of the organ slows metabolism and activates intracellular enzymes, which minimizes the effects of warm ischemia. Unfortunately, hypothermia also results in inhibition of ATP synthesis, cell swelling and intracellular acidity. That is why research is continually being conducted to develop new fluids for rinsing and storing organs as well as to optimize the composition of those that are already in use, which will allow for longer and more effective graft storage and restoration of its optimal functions after transplantation. The article provides current information on rinsing and storage fluids available on the global market. It also discusses the directions of fluid modification with hormones and micronutrients.