Offsetting Cardiac Dysfunction in Acute Spinal Cord Injury to Optimize Neurological Outcome

In the field of spinal cord injury there has been a lot of recent excitement around different drugs and approaches (e.g., stem cells) aimed at improving outcomes for people who sustain a spinal cord injury. The reality, however, is that these approaches are still in their infancy and are likely many years away from being proven effective and becoming widely available. The acutely injured patient that arrives at hospital wants to know what can be done now to improve their chances of keeping as much function as possible. Sadly, one of the only treatment options that is presently available is to manage their cardiovascular system such that blood flow to the injured spinal cord is optimized. Increasing blood flow to the spinal cord is important because it helps to prevent the injury from spreading and impacting more spinal cord tissue, which in turn makes the consequences of the spinal cord injury far worse.

The current approach to managing the cardiovascular system of patients with spinal cord injury is simply to increase blood pressure in all individuals to the same threshold. Although relatively simple, this approach has been shown to improve outcomes in some individuals but to be damaging in other individuals. This suggests that the present approach is not optimal and in fact a more individualized approach is likely to be more appropriate. My laboratory has shown previously that a spinal cord injury affects not only the ability to walk but also affects the health and function of the heart. In fact, we believe this reduced function of the heart happens immediately at the time of spinal cord injury. Since the heart is the major organ in the body responsible for pumping blood to the body, it follows that if heart function is reduced then it is likely contributing to reduced blood flow in the spinal cord. Put a different way, we believe the reduced heart function may be directly leading to impaired outcomes in people with spinal cord injury. We believe that part of the management of people with spinal cord injury when they arrive at hospital should be to increase the function of the heart back to what it was prior to injury such that blood flow to the injured spinal cord can be improved.

In this project, we will explore how the heart changes immediately at the time of injury and during the first hours-to-days after injury. We will also test whether increasing the function of the heart is able to improve spinal cord blood flow and motor outcomes (i.e., ability to move parts of the body below the injury). Since true measurements of heart function and spinal cord blood flow are very 'invasive' (meaning we need to put the tools to measure them inside the heart and spinal cord), we are not able to perform these experiments in humans. Instead, we will use a pig model of spinal cord injury. We have chosen this model because the anatomy of both the heart and spinal cord are very similar to humans, meaning if we find a positive effect in the pig, then it increases our chances of finding a positive effect in humans. To achieve our aims, we will conduct two studies in pigs. The first study will measure how blood flow in the spinal cord changes depending on whether the pig is treated just with blood pressure medication or with the combination of having their heart function returned to pre-injury values and blood pressure medication. The second study will then measure long-term (8 weeks) outcomes in pigs treated with the two different strategies of blood pressure medication alone, or blood pressure medication in combination with heart function.

In addition to conducting the studies in pigs, we will also begin to study how the heart functions in humans during the first 3 days after their injury. Until now, there have been very few studies that have examined how spinal cord injury impacts the heart in this initial period after injury. In this project, we will study heart function once a day for the first 3 days after injury (for a period of 2 hours per day). We will measure how the heart functions while the patient is lying down, and we will next measure how well the heart is able to respond when challenged, by injecting a small amount of fluid into one of their veins. Determining how the heart changes after spinal cord injury is the first step before trialing our pig study in humans to assess whether increasing heart function prevents loss of movement in people with spinal cord injury.