Development of an Algorithm to Perform a Comprehensive Study of Autonomic Dysreflexia in Animals with High Spinal Cord Injury Using a Telemetry Device

The overall goal of this procedure is to characterize the temporal development and progression of autonomic dysreflexia, or AD, using AD detection software in a rodent spinal cord injury model. This is accomplished by first implanting a telemetry device into the abdominal aorta to monitor beat by beat continuous arterial blood pressure and heart rate. 14 days later, the T3 spinal cord segment is completely transected.

Next, AD detection software is used to detect and characterize the spontaneous AD episodes. Alternatively, AD can be induced non-invasively with a Foley catheter, followed by real time monitoring of the induced AD episodes. Ultimately, the episodic hypertension and onset of brachycardia that occurs as a result of the spontaneous or induced AD incidents can be evaluated by the AD detection software.

Allowing sufficient time for implantation of telemetry device prior to spinal cord injury is crucial for animal survival, as mechanical obstruction by telemetry device cause insufficient blood flow to the hind limbs of animals. We used the high thoracic T3 complete spinal cord injury in our protocol, because it induces a number of cardiovascular dysfunctions, including autonomic dysreflexia that resemble the clinical reality of spinal cord injury. The AD detection software that we have developed works by identifying patterns within continuous blood pressure recordings that resemble autonomic dysreflexia, suggesting a possible use for the software in the monitoring of patients with spinal cord injury.

Prior to data collection, implant the catheter of the telemetry device into the abdominal aorta of the animal according to the text protocol. After the telemetry surgery, sample the beat by beat continuous arterial blood pressure of the animal at 1000 hertz in 24 hour blocks to monitor the pre-spinal cord injury hemodynamic parameters. Two weeks later, transect the spinal cord at the T3 segment according to established protocols, followed by monitoring of the arterial blood pressure to assess the post-spinal cord injury response.

To assess the incidence of spontaneous autonomic dysreflexia, or AD, use the appropriate acquisition software to extract the interbeat interval, systolic blood pressure, mean arterial pressure, and time of day from the raw telemetry data over the period of interest. Next, upload a CSV file of the extracted data, including the interbeat interval, the systolic blood and mean arterial pressure values, and the time of day recorded. Then create a threshold for the systolic blood pressure using a moving average window of 240 seconds.

Set the systolic blood pressure transposed threshold at 20 millimeters of mercury above the moving average baseline. Next, identify the systolic blood pressure peak clusters that exceed the transposed threshold with an interpeak interval of less than two seconds, and a peak cluster interval of greater than 10 seconds. Set the AD duration threshold interval to within 120 seconds of each other.

To confirm these peak clusters are associated with a spontaneous AD event, set a minimum heart rate drop restriction associated with the first 10%of the heart rate values upon the onset of the potential event, and 75%of the heart rate values from the end of the potential event. Then subtract the lower heart rate threshold from the higher heart rate threshold to ensure a corresponding drop of 40 BPM or greater, taking care to indicate the relevant physiological range for the systolic blood pressure and heart rate recordings. When all of the panels have been filled click OK.A graphical representation of the detected AD events will be presented, including the spikes in the systolic blood pressure and the associated heart rate data.

A spreadsheet file with the pressure response, duration, maximum systolic blood pressure, minimum heart rate, and heart rate drop of each detected AD event will also be generated. To assess the severity of an induced AD episode, lubricate the tip of a Foley catheter and insert the deflated balloon tip into the rectum of the animal two centimeters from the anal opening. Animals with spinal cord injury have no sensation below the injury, however, they could experience spasmodic and jerky movements during the catheter incretion due to spasticity.

Secure the catheter to the tail with surgical tape and place a custom tube around the outside of the catheter to prevent the rat from biting or pulling out the catheter. Then infuse the balloon with two milliliters of air over 10 seconds. Allow the blood pressure and heart rate to stabilize.

Maintain distension for one minute. After a 10 minute rest, repeat the distention and 10 minute recovery period three more times, and then analyze the severity of induced AD using the AD detection software. Here, a representative recording of the continuous beat by beat arterial blood pressure sampled by the telemetry transducer and extracted by the data acquisition software as just demonstrated is shown.

As these data from continuous arterial blood pressure monitoring demonstrate, spontaneous AD is associated with an increase in the systolic blood pressure greater than 20 millimeters of mercury accompanied by a decrease in the heart rate of 40 BPM or greater upon the onset of the AD event. In these graphs, the rapid and persistent increase in systolic blood pressure accompanied by pronounced brachycardia that occurs after induction of AD by colorectal distention as just demonstrated can be observed. By combining distention with detection and characterization of these spontaneous autonomic dysreflexia events, as just demonstrated, we can study the temporal characteristics of this life threatening condition.