Cryobiology, August 2015, Vol.71(1), pp.169-169
To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.cryobiol.2015.05.024 Byline: Mike Taylor Abstract: Deprivation of a constant and regulated supply of oxygen to cells initiates a progressive series of detrimental events often referred to as the ischemic cascade. This process is unavoidable when a tissue or organ is severed from its blood supply after circulatory arrest and/or excision for transplantation. The cascade of injurious pathways is initiated within minutes of the cessation of oxygen supply. Avoidance or minimization of the intricate interrelated pathways calls for strategic intervention that historically has been centered upon the application of hypothermia in the field of transplantation. In other fields, such as traumatic brain injury and stroke, neuroprotection has been centered on chemical/drug suppression of detrimental pathways in an attempt to avert the cascade of processes that ultimately result in cell death by necrosis, apoptosis, or a combination of these mechanisms. Such strategies are focused on short-term events and transient ischemic attacks. However, in the context of the long-term preservation of tissues and organ banking for transplantation, the application of hypothermia has proved to be the bedrock strategy providing effective methods of preservation and storage to meet the current practices of organ transplantation. This approach is not without severe limitations since hypothermia is a double-edged sword. Hypothermia is globally protective due to its inherent suppression of chemical pathways on the basis of thermodynamics and Arrhenius kinetics. In this way, the demand for oxygen is markedly reduced due to the suppression of metabolic processes and detrimental pathways are also slowed by reduction of temperature. However, cooling per se causes undesirable responses in the cell such that as interventionalists (clinicians and researchers) we have learned to strike a balance to counteract the detrimental effects of cooling in order to harness the protective properties of hypothermia during ischemia and hypoxia. The name of the game is to understand how a cell responds to cold in relation to the ischemic cascade and translate this into how we can control the environment of the cell directly, and the internal environment indirectly, in order to optimize preservation and protection. This is the principle upon which organ preservation solutions have been designed and developed and formed the basis of current methods that have existed for several decades. Future developments are unlikely to come from further minor modifications to the present-day base formulations. Nevertheless, these tried-and-tested solutions provide the necessary baseline for including additional cytoprotective agents aimed at targeting specific pathways in the ischemia/reperfusion cascade. Such additives will include pharmacologics, biochemicals, oxygen-carriers and cryoprotective agents added to the baseline preservation solutions to enhance cellular preservation-protection-resuscitation. Delivery of these agents to the cells comprising complex tissues and organs will demand new technologies with a wide range of potential candidates on the horizon.
View record in ScienceDirect (Access to full text may be restricted)