Reperfusion injury

The restoration of blood flow to ischemic tissues causes additional damage, which is termed reperfusion injury. All tissues are susceptible to reperfusion injury, but this susceptibility varies between tissues. Reperfusion has wide clinical relevance. It influences the outcome of patients after myocardial infarction, stroke, organ transplantation, and cardiovascular surgery. Advances in the treatment of reperfusion injury have created an opportunity for plastic surgeons to apply these treatments to flaps and reimplanted tissues. The main putative mechanisms identified in animal models involve leukocyte-endothelium interactions, reactive oxygen species, and the complement system. However, it has become evident that these fundamental biological systems are controlled by many interrelated pathways. Attempts to bypass this complexity have led to a search for the early "upstream" initiating events, rather than the "downstream" cascading events. This contrasts with current clinical efforts that are directed toward hypothermia, intraarterial flushing, and preconditioning. This article outlines the molecular and cellular events that occur during reperfusion injury and then reviews the efforts that have been made to exploit this knowledge for clinical advantage.     

Reperfusion injury

Several lines of evidence point to a major role of oxygen free radicals in the pathogenesis of cell death or dysfunction in a variety of disease processes. Recent studies from this as well as other laboratories have demonstrated that oxygen free radicals play a major role in the pathogenesis of post-ischemic reperfusion injury in the heart. We have recently developed methods for direct measurement of radical species and/or specific byproducts of radical injury. Timely administration of oxygen radical scavengers reduced the quantity of free radicals generated following reperfusion and in addition improved recovery of post-ischemic ventricular function and metabolism. In a regionally ischemic model the free radical scavenger recombinant human superoxide dismutase also administered at the time of reflow was shown to limit infarct size. In this article we review the biophysical and molecular mechanisms of oxygen free radical generation that are viewed as contributing to post-ischemic reperfusion injury. We also discuss the mechanisms by which the body defends against free radical attack and the interrelationships of free radical injury to other mechanisms of tissue injury.     

An axonal strain injury criterion for traumatic brain injury

Computational models are often used as tools to study traumatic brain injury. The fidelity of such models depends on the incorporation of an appropriate level of structural detail, the accurate representation of the material behavior, and the use of an appropriate measure of injury. In this study, an axonal strain injury criterion is used to estimate the probability of diffuse axonal injury (DAI), which accounts for a large percentage of deaths due to brain trauma and is characterized by damage to neural axons in the deep white matter regions of the brain. We present an analytical and computational model that treats the white matter as an anisotropic, hyperelastic material. Diffusion tensor imaging is used to incorporate the structural orientation of the neural axons into the model. It is shown that the degree of injury that is predicted in a computational model of DAI is highly dependent on the incorporation of the axonal orientation information and the inclusion of anisotropy into the constitutive model for white matter.     

A proposed injury threshold for mild traumatic brain injury

Traumatic brain injuries constitute a significant portion of injury resulting from automotive collisions, motorcycle crashes, and sports collisions. Brain injuries not only represent a serious trauma for those involved but also place an enormous burden on society, often exacting a heavy economical, social, and emotional price. Development of intervention strategies to prevent or minimize these injuries requires a complete understanding of injury mechanisms, response and tolerance level. In this study, an attempt is made to delineate actual injury causation and establish a meaningful injury criterion through the use of the actual field accident data. Twenty-four head-to-head field collisions that occurred in professional football games were duplicated using a validated finite element human head model. The injury predictors and injury levels were analyzed based on resulting brain tissue responses and were correlated with the site and occurrence of mild traumatic brain injury (MTBI). Predictions indicated that the shear stress around the brainstem region could be an injury predictor for concussion. Statistical analyses were performed to establish the new brain injury tolerance level.     

Traumatic brain injury

There is an increasing incidence of military traumatic brain injury (TBI), and similar injuries are seen in civilians in war zones or terrorist incidents. Indeed, blast-induced mild TBI has been referred to as the signature injury of the conflicts in Iraq and Afghanistan. Assessment involves schemes that are common in civilian practice but, in common with civilian TBI, takes little account of information available from modern imaging (particularly diffusion tensor magnetic resonance imaging) and emerging biomarkers. The efficient logistics of clinical care delivery in the field may have a role in optimizing outcome. Clinical care has much in common with civilian TBI, but intracranial pressure monitoring is not always available, and protocols need to be modified to take account of this. In addition, severe early oedema has led to increasing use of decompressive craniectomy, and blast TBI may be associated with a higher incidence of vasospasm and pseudoaneurysm formation. Visual and/or auditory deficits are common, and there is a significant risk of post-traumatic epilepsy. TBI is rarely an isolated finding in this setting, and persistent post-concussive symptoms are commonly associated with post-traumatic stress disorder and chronic pain, a constellation of findings that has been called the polytrauma clinical triad.