Name: development of an algorithm to perform a comprehensive study of autonomic dysreflexia in animals with high spinal cord injury using a telemetry device
Uploaded: 2016-07-29T13:00:00
Description: Watch this Scientific Journal Video about Development of an Algorithm to Perform a Comprehensive Study of Autonomic Dysreflexia in Animals with High Spinal Cord Injury Using a Telemetry Device at JoVE

This research if funded by the Canadian Institute of Health Research and the Heart and Stroke Foundation of BC and Yukon.&#160;We would like to acknowledge Mr. Rayshad Gopaul and Dr. Shelly McErlane for technical support and expertise in animal care.

Male Wistar (Hsd: WI Wistar) rats at 7 weeks of age and weighing 300-350 g were used in this experiment. All rats were maintained on a 12&#160;hr light/dark cycle and received standard laboratory rat chow and water ad libitum. All experimental procedures conformed with the guide to the Care and Use of Experimental Animals established by the Canadian Council on Animal Care and granted ethics approval by the University of British Columbia. Surgery and animal care were conducted according to standard procedures in our labor...

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The protocol describes a detailed implementation of a novel JAVA platform AD Detection software which would be combined with a telemetry device, for a long-term thorough analysis of ABP in SCI-animals (Figure&#160;1B). This is the first software that allows for the characterization of ABP patterns to detect spontaneous AD events as they occur sporadically throughout the duration of the day. A well-characterized T3 SCI animal model can illustrate the functional capacity of the software to detect the frequ...

Autonomic dysreflexia (AD) is a life-threatening emergency in individuals after acute or chronic spinal cord injury (SCI) at cervical or high-thoracic segments and is usually characterized by episodes of persistent hypertension and bradycardia1. AD is principally caused by disruption of descending spinal pathways that usually provide input from supraspinal centers to the spinal sympathetic preganglionic neurons that control sympathetic activity and vascular tone1-4. AD episodes are characterized by a spike in systolic blood pressure (SBP) up to 300 mmHg and if left untreated may lead to seizures, intracranial hemorrhage, myocardial infarction, and even death5-8. A variety of noxious and non-noxious stimuli act as a trigger of AD, including bowel and bladder distension, spasms, pressure sores, urinary bladder catheterization or iatrogenic procedures9-12.
The temporal development of AD in response to SCI has been investigated in both human9 and animal models13,14. Typically these studies have used an &#8216;induced AD&#8217; method (i.e., urodynamics, penile vibrostimulations in humans or colorectal distension in animals) to determine the temporal development of AD. Such an approach is limited by the need for repeated assessments at isolated time-points that may preclude an accurate determination of the temporal development of AD. The use of 24-hr blood pressure monitoring in humans allows serial blood pressure measurements to be made at pre-determined intervals. This technique has recently been employed to monitor spontaneously occurring AD in patients with chronic SCI. In animal models, solid-state pressure transducers are being increasingly used to chronically monitor beat-by-beat arterial blood pressure. Recently, Rabchesvky et al. (2012), developed an algorithm that extracted one second averages of mean arterial pressure (MAP) and compared against a moving average threshold15. Spontaneous AD events were characterized based on MAP peaks that are 10 mmHg or greater above threshold concurrently with a HR drop of 10 bpm or greater.
Here a novel JAVA software that has a built in AD Detection Algorithm is presented. This algorithm works by detecting pre-determined patterns in arterial blood pressure (ABP) and heart rate (HR) that are indicative of a spontaneously occurring AD event. The user is able to manually adjust all input variables to the software such that the &#8216;detection algorithm&#8217; can be easily customized to the specific parameters of interest. The software is also able to dichotomize ABP and HR into a given epoch such that diurnal rhythmicity of hemodynamic parameters can be analyzed16. In the present manuscript, a detailed explanation is given of the surgical technique that is used to implant the telemetry devices and conduct the SCI surgery. Examples are also provided with respect to&#160;the post-processing capabilities of the AD Detection software and how cardiovascular function is altered post-SCI. For comparative purposes, the methodology and results obtained from a method of induced AD known as colorectal distension (CRD) is also illustrated.

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development of an algorithm to perform a comprehensive study of autonomic dysreflexia in animals with high spinal cord injury using a telemetry device

Spinal cord injury (SCI) is a debilitating neurological condition characterized by somatic and autonomic dysfunctions. In particular, SCI above the mid-thoracic level can lead to a potentially life-threatening hypertensive condition called autonomic dysreflexia (AD) that is often triggered by noxious or non-noxious somatic or visceral stimuli below the level of injury. One of the most common triggers of AD is the distension of pelvic viscera, such as during bladder and bowel distension or evacuation. This protocol presents a novel pattern recognition algorithm developed for a JAVA platform software to study the fluctuations of cardiovascular parameters as well as the number, severity and duration of spontaneously occurring AD events. The software is able to apply a pattern recognition algorithm on hemodynamic data such as systolic blood pressure (SBP) and heart rate (HR) extracted from telemetry recordings of conscious and unrestrained animals before and after thoracic (T3) complete transection. With this software, hemodynamic parameters and episodes of AD are able to be detected and analyzed with minimal experimenter bias.

Using telemetry, arterial blood pressure is sampled at a frequency of 1,000 Hz continuously for 24 hr. An illustrative recording of arterial blood pressure (ABP) using LabChart is shown in Figure 1B. The sample ABP was monitored by a solid state pressure sensor inserted into the descending aorta. The novel JAVA platform AD Detection software is able to extract relevant SBP (mmHg) peaks (Figure&#160;1C). We may also extract the HR (bpm) from the time interval between adjacent SBP peaks (<...

Watch this Scientific Journal Video about Development of an Algorithm to Perform a Comprehensive Study of Autonomic Dysreflexia in Animals with High Spinal Cord Injury Using a Telemetry Device at JoVE

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

The catheter of a telemetry device is implanted into the abdominal aorta in order to continuously collect beat-by-beat hemodynamic data from animals pre and post-high thoracic spinal cord transection. A novel JAVA software was employed to analyze hemodynamic parameters as well as frequency and intensity of spontaneous episodes of autonomic dysreflexia.

Spinal cord injury (SCI) is a debilitating neurological condition characterized by somatic and autonomic dysfunctions. In particular, SCI above the ...

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.

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Medicine

Acute and Chronic Tactile Sensory Testing after Spinal Cord Injury in Rats

Spinal cord injury (SCI) impairs sensory systems causing allodynia1-8. To identify cellular and molecular causes of allodynia, sensitive and valid sensory ...

A Contusive Model of Unilateral Cervical Spinal Cord Injury Using the Infinite Horizon Impactor

While the majority of human spinal cord injuries occur in the cervical spinal cord, the vast majority of laboratory research employs animal models of ...

A Contusion Model of Severe Spinal Cord Injury in Rats

The translational potential of novel treatments should be investigated in severe spinal cord injury (SCI) contusion models. A detailed methodology is ...

Evaluation of Respiratory Muscle Activation Using Respiratory Motor Control Assessment (RMCA) in Individuals with Chronic Spinal Cord Injury

Evaluation of Respiratory Muscle Activation Using Respiratory Motor Control Assessment RMCA in Individuals with Chronic Spinal Cord Injury

During breathing, activation of respiratory muscles is coordinated by integrated input from the brain, brainstem, and spinal cord. When this coordination ...

A Murine Model of Cervical Spinal Cord Injury to Study Post-lesional Respiratory Neuroplasticity

A cervical spinal cord injury induces permanent paralysis, and often leads to respiratory distress. To date, no efficient therapeutics have been developed ...

Controlled Cortical Impact Model for Traumatic Brain Injury

Every year over a million Americans suffer a traumatic brain injury (TBI).  Combined with the incidence of TBIs worldwide, the physical, emotional, ...

A Radio-telemetric System to Monitor Cardiovascular Function in Rats with Spinal Cord Transection and Embryonic Neural Stem Cell Grafts

High thoracic or cervical spinal cord injury (SCI) can lead to cardiovascular dysfunction. To monitor cardiovascular parameters, we implanted a catheter ...

Synergetic Use of Neural Precursor Cells and Self-assembling Peptides in Experimental Cervical Spinal Cord Injury

Spinal cord injuries (SCI) cause serious neurological impairment and psychological, economic, and social consequences for patients and their families. ...

Calibrated Forceps Model of Spinal Cord Compression Injury

Compression injuries of the murine spinal cord are valuable animal models for the study of spinal cord injury (SCI) and spinal regenerative therapy. The ...

Contrast Enhanced Ultrasound Imaging for Assessment of Spinal Cord Blood Flow in Experimental Spinal Cord Injury

Reduced spinal cord blood flow (SCBF) (i.e., ischemia) plays a key role in traumatic spinal cord injury (SCI) pathophysiology and is accordingly an ...