The overall goal of the following experiment is to describe a gold standard for evaluating orthostatic tolerance. This test can be combined with non-invasive evaluations of cardiovascular reflex control after a 20 minute period of supine. Rest subjects are head upright tilted for 20 minutes.
After this time, lower body negative pressure is applied at negative 20, negative 40 and negative 60 millimeters of mercury for 10 minutes each until pres syncope is reached, results are obtained that show normal and abnormal responses according to age and gender. The main advantages of this technique over existing methods are its noninvasive nature and ability to provoke pres syncope in all individuals tested. The implications of this technique extend toward therapy or diagnosis of unexplained syncope because of its high sensitivity, specificity, and repeatability.
Demonstrating the procedure will be Jessica Inskip and Rihanna Ravens Bergen graduate students from my laboratory. Another of my graduate students, Claire Prothero, will be acting as the volunteer for the purposes of filming. The manually adjustable tilt table is capable of moving from minus 15 to plus 60 degrees in 10 degree increments.
It includes an adjustable right arm rest with an adjustable holder for a brachial ultrasound probe, an adjustable foot plate for the subject to stand on and a seatbelt to secure the subject's legs. A lower body negative pressure or LBNP chamber with an attached pressure gauge fits into a wooden groove filled with neoprene on the bottom half of the tilt table. It is secured in place by four adjustable straps.
Attach a wooden waste board to the top of the chamber with a neoprene surround at the level of the subject's iliac crest to provide an airtight seal with the chamber. Perform continuous beat to beat data acquisition with a sampling frequency of one kilohertz, using an analog to digital converter and visualize all data simultaneously in real time throughout testing. Using lab chart.
Conduct the testing in a temperature controlled room to avoid the known effect of heat stress upon orthostatic tolerance. Ideally conduct tests in the mornings because of the effect of diurnal rhythms on barrow reflex control. In some cases, a familiarization session is advised to minimize the influence of a stress response on the procedure.
Instruct subjects to have only a light breakfast and to fast for two hours prior to testing, as well as to avoid caffeine and strenuous exercise on the morning of testing. They should also abstain from drinking alcohol for 24 hours prior to testing. An outline of the protocol can be seen here.
To begin, stand the subject on the table, foot plate and move him or her into a supine position. Once supine, align the iliac crest with the center of the table. This allows for ease of tilting and ensures standardized positioning of the LBNP chamber.
Adjust the footplate accordingly. Next loosely, position a strap just above the knee to promote passive standing and provide postural support. Instruct the subject not to move his or her legs during testing.
Position the subject's right arm on the armrest and adjust so that it is comfortably supported at heart level. Now attach all monitoring equipment to be used. Beat to beat.
Blood pressure monitoring will be conducted using the phenome. Choose the finger cuff that fits appropriately into the middle phalanx of the subject's right middle finger. Use a brachial cuff to internally calibrate the phenome prior to data collection.
Enter the subject's sex, age, height, and weight into the phenomen to enable appropriate assumptions for the model flow algorithms. Next, apply ECG electrodes in a modified lead two configuration, ensuring that the electrode sites do not interfere with positioning of the neoprene waste board. Continuous ECG monitoring is crucial for the accurate determination of heart rate responses and prompt identification of any cardiac arrhythmia should they occur.
Next, set up to record peripheral vascular responses with Doppler ultrasound. With the right arm at heart level, palpate the brachial artery until the pulse is located. Then apply ultrasound gel and position an eight megahertz ultrasound probe so that a brachial artery velocity waveform is obtained.
Once the signal is identified, optimize the depth and gain and tighten the adjustable holder to assure that the angle of insulation remains constant for the duration of the test. Next determines cerebral vascular responses. Similarly, secure the cerebral ultrasound probe in place using a plastic headset or fabric headbands to ensure faithful signal detection and a constant angle of insulation throughout testing.
Determine blood velocity continuously from the middle cerebral artery. Apply ultrasound gel to the subject's temple and locate the vessel once identified. Again, optimize the depth and gain settings.
This vessel is chosen because of its convenience of identification. Large contribution to global cerebral perfusion and constant diameter during orthostatic stress. Now, attach the nasal cannula.
Nasal sampling is preferred because it permits the subject to talk freely during testing and report symptoms while avoiding invasive blood sampling that may adversely impact orthostatic tolerance. Encourage subjects to breathe through the nose. Place the LBNP chamber on the table and secure it with the straps.
Then select a waste board that fits snugly so that an airtight seal with the neoprene can be achieved. The wooden component of the waste board should not be touching the subject. Secure the waste board to the chamber, then connect the chamber to a negative pressure source via a variable resistor.
First record data for 20 minutes In the supine position, shorter rest periods are associated with greater falls in blood pressure when upright, presumably because the reabsorption of any fluid that has collected in the dependent limbs prior to lying down is not yet complete, then at the end of the supine phase, maneuver the table to a tilt angle of 60 degrees. This angle is preferred because it affords nearly 90%of the maximal vertical displacement while allowing the subject to remain relaxed and supported against the table, less steep angles may increase the false negative rate. Complete the transition to upright within 30 seconds.
Continuously monitor the subject's cardiovascular parameters as well as subjective experience. The test should be stopped immediately and the subject return to a supine position. If any of the endpoint criteria seen here are met, unless there is a specific desire to initiate syncope, terminate the test rapidly at the onset of presyncopal signs and symptoms, avoiding frank syncope.
After 20 minutes of tilting, inform the subject of the impending onset of LBNP to prevent a startle response. Then apply LBNP while still tilted at negative 20 millimeters of mercury for a further 10 minutes. After 10 minutes, increase the LBNP to negative 40 millimeters of mercury for another 10 minutes.
Then after 10 minutes, increase the LBNP to negative 60 millimeters of mercury and continue for another 10 minutes. At the end of this phase, turn off the LBNP orthostatic tolerance is defined as the time to pres syncope in minutes from the onset of the head up tilting phase. After the subject reports symptoms of pres syncope rapidly return the table to a supine or even slightly head down position to minimize the likelihood of syncope or asystole.
This image shows the blood pressure and the brachial and middle cerebral artery blood flow velocity before and after a test is terminated due to pres syncope. The test was terminated when the blood pressure decreased to 70 over 42 millimeters of mercury. After the test was terminated and the subject quickly returned to the supine position, the blood pressure and cerebral blood flow velocity were restored within five to six heartbeats.
The loss of the brachial signal was caused by the movement of the ultrasound probe due to the rapid movement of the table into the supine position. Returning the table to a slightly head down position of about negative 15 degrees may promote faster resolution of the presyncopal event. Once all variables have returned to the supine levels and any symptoms are resolved, remove the monitoring equipment.
Then after removing the LBNP chamber, remove the strap over the subject's legs and lower the foot plate to its original position. Ensure the subject is positioned with their feet on the plate before returning the table to an upright position, instruct the subject to tense his or her leg muscles throughout the transition to avoid any symptoms from reoccurring. As the table is tilted to facilitate getting up, ask the subject to sit after stepping off the table to ensure they are symptom free before leaving the laboratory.
Typical values for orthostatic tolerance in healthy volunteers according to age and gender can be seen here. Patients with orthostatic intolerance, exhibit pres syncope earlier in the test with 85%ending the test within the negative 20 millimeters of mercury phase. Compared to 23%of controls, the threshold of normal is taken as the 20%incidence of syncope.
A representative response in an adult control is depicted here, beat to beat blood pressure, electrocardiogram, brachial, and cerebral blood flow velocity are shown during the orthostatic stress. A progressive barrow reflex mediated tachycardia and vasoconstriction can be seen. At pres syncope, the barrow reflex begins to fail and there is a drop in blood pressure and cerebral blood flow velocity.
Using this protocol, all subjects experience pres syncope and the definition of normal or abnormal responses is made largely based upon the time it takes to induce this reaction. The hemodynamic responses can also be qualified, and this is described in the manuscript text During this procedure. Other methods such as micrography or impedance plethysmography can be performed in order to provide additional information on sympathetic regulation of vascular resistance and the magnitude of fluid losses due to venous pooling or capillary filtration.
This technique is highly reproducible, has the ability to discriminate normal and abnormal responses with high sensitivity and specificity. It can provoke pres syncope in all subjects allowing for symptom recognition in patients with recurrent syncope. In a clinical setting, different types of syncope can be distinguished, allowing tailored treatment and management approaches.
The impact of interventions can be readily assessed with additional cardiovascular monitoring. Reflex responses can also be evaluated.
