Optimizing Hemodynamic Support of Acute Spinal Cord Injury Based on Injury Mechanism

Few injuries are as physically and psychologically devastating as suffering a spinal cord injury (SCI). Each year, over ten thousand North Americans suffer such an injury and are left permanently paralyzed, with limited to no movement of their arms and/or legs and a myriad of other health impairments such as bowel and bladder incontinence. Unfortunately, there are no treatments available that unequivocally reverse this paralysis and improve neurologic recovery. Much research has been done to develop novel therapies for SCI in the laboratory. While these are promising, it will still be many years before the completion of clinical trials that test their effectiveness in human SCI. This is little comfort to those who are injured today, particularly in combat situations where advanced and sophisticated neuro-restorative therapies may simply not be deliverable. There is therefore an urgent need for treatments that can be more rapidly translated into the clinical setting to improve neurologic recovery in individuals who have suffered an acute spinal cord injury.

Our research proposal aims to inform current treatment guidelines around the blood pressure management of acute SCI. Blood pressure management in acute SCI is important because after traumatic injury the spinal cord's blood supply is reduced below critical levels, making the cord vulnerable to further irreversible ischemic injury. Physicians attempt to improve the blood supply by increasing systemic blood pressure for the first week post-injury. Current practice guidelines recommend using intravenous fluids and vasopressors to maintain the mean arterial pressure (MAP) at 85-90 mm Hg for 5-7 days post-injury in all acute SCI patients. These guidelines, however, are not based on strong clinical evidence from high-quality clinical trials. By promoting a 'one-size-fits-all' approach, such hemodynamic guidelines ignore the possibility that the spinal cord and its blood flow respond differently depending upon whether the cord remains compressed or has been surgically decompressed after a period of prolonged compression lasting hours to days.

The ultimate goal of our research is to inform clinical guidelines around the hemodynamic management of acute SCI patients by determining how alterations in systemic blood pressure influence the injured spinal cord before and after surgical decompression. Our overall objective is to determine how hemodynamic support of systemic blood pressure in the presence or absence of spinal cord compression affects the vascular, metabolic, biochemical, and behavioral outcomes of traumatic SCI. It is our hypothesis that increasing the blood pressure to improve blood supply to the injured spinal cord is helpful when the cord remains compressed, but, paradoxically, has deleterious effects when the cord is surgically decompressed. Our pilot data using a large animal model of SCI have suggested that increasing the blood pressure after decompression leads to dramatically increased swelling of the spinal cord and an exaggerated metabolic response. Such deleterious effects were hinted at many years ago, but these warnings have to some extent been overlooked in our current enthusiasm for driving up the blood pressure.

To shed further light on the downstream effects of hemodynamic support, we will use a novel pig model of SCI that shares many anatomic and physiologic similarities with human SCI. The pig spinal cord is much more similar in size to the human cord than the rat or mouse spinal cord. Similarities in the pig spinal cord blood supply with that of humans have made it a routinely used animal model for studies of ischemic spinal cord injury. Using our large animal model of SCI, we hypothesize that well-intended increases in MAP will exacerbate a so-called 'reperfusion injury' and ultimately have deleterious effects on regions of the spinal cord surrounding the injury site. Our experiment will evaluate both short-term (24 hours post-injury) and long-term (12 weeks post-injury) outcomes of MAP support before and/or after spinal cord decompression has occurred.

Ultimately, a better understanding of how the spinal cord adjacent to the injury site responds to alterations in systemic blood pressure in the presence or absence of residual mechanical compression will help clinicians provide optimal hemodynamic management for patients with acute SCI and improve their chances of neurologic recovery. This research has potential application to all patients with acute SCI, and importantly is relevant to front-line clinicians who are charged with managing these individuals and doing whatever possible to maximize their chances of neurologic recovery. Blood pressure management is one of the few aspects of clinical care in acute SCI that physicians currently have some control over, and so it is highly relevant to seek ways of optimizing this management. We do not discount the importance of novel and cutting-edge neuro-regenerative therapies -- clearly, these will be needed to advance the field of SCI research in the future. However, we contend that work such as that which we propose is important to understand how we could potentially improve the delivery of care today.