Recent evidence suggests that concussions may disrupt autonomic cardiovascular control. This study investigated the initial effects of concussion on cardiovascular function using three autonomic reflex tests. Twenty-three recreational athletes (12 women, 11 men) were divided into concussed (n = 12) and control (n = 11) groups. Concussed participants performed forced breathing, standing, and Valsalva autonomic tests four times: 1) within 48 h of injury; 2) 24 h later; 3) 1 wk after injury; and 4) 2 wk after injury. The controls performed the same tests on the same schedule. Differences in heart rate (HR), systolic blood pressure (SBP), and diastolic blood pressure (DBP) responses to the tests were continuously measured using finger photoplethysmography and were analyzed using repeated-measures multivariate ANOVAs and ANOVAs. Within 48 h of injury, the concussed group had significantly greater resting SBP (t21 = 2.44, P = 0.02, d = 1.03), HR (t21 = 2.33, P = 0.03, d = 1.01), and SBP responses to standing (t21 = 2.98, P = 0.01, d = 1.24), and 90% SBP normalization times (t21 = 2.64, P = 0.02, d = 1.10) after the Valsalva, but those group differences subsided 24 h later. There was also a significant interaction with the HR responses to forced breathing (F3,60 = 4.13, P = 0.01, ηp2 = 0.17), indicating the concussed responses declined relative to the control’s over time. The results demonstrate that concussion disrupted autonomic cardiovascular control, and that autonomic reflex tests are practical means by which to evaluate that dysfunction.
- brain injury
there are an estimated 1.6–3.8 million concussions that occur annually in the United States (33); however, this likely underestimates the true incidence, as many concussions go unrecognized or unreported (40, 44, 47). Once thought to be a transient physiological injury, concussions are now believed to include both structural pathology (e.g., cerebral microbleeds) and neurophysiological alterations and may be associated with long-term neurological complications (20, 21, 39, 45, 53). Indeed, several studies have suggested that there is a relationship between recurrent concussions and multiple later life neuropathologies, including elevated risk of Alzheimer’s disease, mild cognitive impairment, clinically diagnosed depression, and potentially chronic traumatic encephalopathy (20, 21, 45).
The currently recommended and widely utilized clinical assessment of concussion involves a multifaceted test battery, including balance, cognition, and self-reported symptoms (7, 27, 44). While underreporting of concussions remains highly problematic, this multifaceted approach is highly sensitive to the diagnosis of concussion (0.89–0.96) once a concussion is suspected (6); however, there is limited insight into the central neurological deficits (14). The pathophysiology of concussion is predominantly a functional neurometabolic cascade that includes an ionic flux with indiscriminate glutamate release and potassium efflux, along with a sodium and calcium influx, resulting in a cerebral energy crisis secondary to impaired mitochondrial function (14). This widespread ionic flux has been described as a diffuse “spreading depression” with widespread areas of the brain affected simultaneously (15). Advanced imaging modalities (e.g., functional MRI, diffusion tensor imaging) have identified multiple pathological features; however, the associations between imaging findings and cognitive performance is not well established (14, 38). Thus imaging alone has not fully elucidated the pathophysiology of concussion, and further understanding of the central alterations postconcussion are needed.
Among the many areas of the brain that are typically damaged in closed head injury (e.g., ischemic injury, intracranial hemorrhage, and head trauma) are the nucleus tractus solitarii and both the caudal and rostral ventrolateral medullae, which can uncouple the relationship between the autonomic cardiovascular systems (17). Cardiovascular autonomic dysfunction (CVAD) has been suggested as a potential biomarker for concussion recovery (32). Heart rate variability (HRV) offers a particularly appealing method for making such decisions because it is a clinically feasible, relatively simple, and noninvasive means by which to evaluate the interaction of the autonomic parasympathetic (PNS) and sympathetic nervous systems (SNS). However, results to date have been inconsistent, as some studies have found transient abnormalities in HRV at rest (17, 18, 24, 28, 30, 49, 50, 54), as well as during isometric handgrip exercise (1) and aerobic exercise (12, 13), whereas others have failed to identify these changes at rest (1, 13, 29, 31) or during isometric handgrip exercise (31). Still, other measures have been used to confirm the link between concussion and autonomic dysfunction, including the pupillary light reflex (8) and pulse-wave analysis during isometric hand grip exercise (32). Furthermore, both Kozlowski et al. (29) and Leddy et al. (34) observed that concussed patients exhibited abnormal blood pressure (BP) responses during graded exercise testing. Those two studies, along with several others (9, 35, 48), also found that the dysfunction-associated concussion can lead to exercise intolerance that persists well beyond 7–10 days.
Another type of physical limitation that has been used to identify and assess CVAD following concussion is orthostatic intolerance. Studies by Heyer et al. (23) and Kanjwal et al. (26) have found that concussions can lead to postural tachycardia syndrome, which is often characterized by both abnormally large increases in heart rate and lightheadedness with upright posture. Most concussed individuals do not typically develop this syndrome, but lightheadedness and postural disturbances are among the most common symptoms reported after a concussion (2, 22, 42). Although the common view has been that these symptoms are related to vestibular dysfunction, an alternative hypothesis postulates that autonomic dysfunction is the major cause of dizziness following concussion (19). Those investigators further concluded that concussion-induced CVAD can be recognized by monitoring HR and BP responses to standard autonomic tests of orthostatic tolerance and cardiovagal function. The potential advantage of using standard autonomic tests, such as forced breathing, standing, and the Valsalva maneuver, to assess concussive injury is that they are well-validated and highly reliable clinical tests of CVAD (3, 11, 41, 56) and they do not require participants to unduly exert themselves. Thus the purpose of the present study was to investigate cardiovascular responses during forced breathing, standing, and the Valsalva maneuver over the typical 2-wk recovery time following a concussion (44). We hypothesized that concussion would cause abnormal autonomic and cardiovascular responses, and that the abnormalities would diminish or resolve throughout the 2-wk period of recovery.
MATERIALS AND METHODS
A convenience sample of 23 college students participated in this investigation. (Table 1). The 12 concussed participants (concussed) were initially diagnosed by certified athletic trainers, and the diagnosis was confirmed by a physician based on standard diagnostic criteria (44). All 12 of those individuals had suffered their concussion while they were participating in a sport. Concussed participants were matched to a control participant (control) by sex, height, and mass. Control participants were excluded if they had a history of either prior concussion or neurological diseases. All participants were involved in recreational athletic activities, but none was an intercollegiate athlete or actively engaged in an intensive exercise training program. The university’s institutional review board approved this study and data collection procedures, and all the participants provided written, informed consent immediately before their enrollment in the study.
All concussed participants were tested on four occasions: 1) acute (within 48 h postconcussion); 2) subacute (24 h after the acute test); 3) week 1 (7 days postconcussion); and 4) week 2 (14 days postconcussion). The control participants were tested using the same time intervals. The testing schedule was selected to be consistent with previous research (5), and the same protocol was used for all testing sessions.
All of the arterial BP and heart rate measurements in this investigation were continuously and noninvasively monitored using finger photoplethysmography (Finometer Pro, Finapres Medical Systems, Amsterdam, The Netherlands), consistent with established protocols. Specifically, on arrival at the laboratory, participants were instructed to warm the fingers on their nondominant hand (e.g., by massaging them or running them under warm water) to better ensure there was no reduction in blood flow due to cold fingers. The participants were then fitted with both a cuff around the middle finger and one at midheart level around the upper arm of the nondominant arm. Participants were instructed to lay quietly in the supine position for 5 min, during which time the experimental procedures were explained, and a return to flow calibration was performed to confirm the accuracy of the finger cuff measurements. Participants then performed the standard cardiovascular reflex testing protocol recommended by Wieling and Karemaker (56), which consisted of the following progression: 1) a forced breathing test while in the supine position; 2) a 3-min recovery period in the supine position; 3) standing for 5 min; 4) a 3-min recovery period while seated; and 5) a Valsalva maneuver performed while seated. The Physiocal function of the Finopres remained on throughout most of the protocol, but it was turned off during the first 70 s of each of the three experimental tests. Once the testing protocol was completed, the data were downloaded into an Excel file for further analysis.
Forced breathing test.
While supine, participants maximally inhaled over the course of 6 s and then maximally exhaled over the course of 6 s, eight consecutive times. An investigator helped each participant stay on task by counting out loud (e.g., “inhale, 1, 2, 3 4, 5, now exhale, 1, 2, 3, 4, 5…”). This test is considered optimal for determining cardiovagal function (3), as forced inhalation results in an increase in heart rate, whereas expiration results in increased vagal tone and consequent decrease in heart rate (Fig. 1). The purpose of this test is to determine the mean variation in HR (HRdiff) (11, 41, 56). In this investigation, the HRdiff was determined using the following equation: The HRmax and HRmin means are the mean peak HR resulting from the eight forced inspirations and the mean lowest HR resulting from the eight forced expirations, respectively. As is typical of standard forced breathing tests of autonomic function (11, 41, 56), BPs were not evaluated during this test in the present investigation.
After the forced breathing test and nearly 10 min of lying in the supine position, the last 3 min of which were spent quietly resting, participants stood up and remained standing for 5 min. Investigators encouraged participants to stand over the course of no more than a few seconds and to remain as still as possible throughout standing. As one stands, there is typically an immediate decline in systolic (SBP) and diastolic BP (DBP), as well as an increase in HR due mostly to the baroreflex (11, 41, 56). Approximately 5–10 s later, there is usually a rapid overshoot in SBP and DBP, along with a progressive decline in HR, which are mediated by the baroreflex (Fig. 2). Because the highest HR typically occurs at about the 15th beat after standing and the lowest HR typically occurs at about the 30th beat, the pertinent measurement of interest is typically the 30:15 ratio (3, 11, 41, 56). However, Wieling and Karemaker (56) have observed that the 30:15 ratio does not accurately reflect the true HR maximum (HRmax) and minimum (HRmin) in all individuals, and so they recommend using the actual HRmax and HRmin values that were measured within the first 30 s of standing instead. Therefore, the HR responses to standing were evaluated using the HRmax-to-HRmin ratio (HRmax/HRmin) in this investigation. With respect to SBP and DBP, the initial decrease (SBPunder and DBPunder), subsequent overshoot (SBPover and DBPover), and mean standing responses (SBPstand mean and DBPstand mean) were investigated. The SBPunder and DBPunder scores were both determined using the following equation: The SBPover and DBPover scores were both determined using the following equation:The pressure baseline mean was the pressure taken during the last 20 s in the supine position before standing. The pressure low score was the lowest pressure value measured immediately after standing, and the pressure overshoot score was the highest pressure value measured during the subsequent rapid recovery in pressure. The SBPstand mean and DBPstand mean scores were the pressure means taken during the final 4 min of the standing test.
After 3 min of quiet sitting, participants forcefully exhaled through a flexible 75-mm hematocrit tube for 15 s. Participants were instructed to first take a normal inhalation, and then form a tight seal around the tube with their lips and blow as hard as they could for the duration of the test. When a Valsalva test such as this is performed, SBP and DBP typically respond in four phases (3, 11, 41, 56). In the first two phases, the pressure initially rises for a few seconds due to mechanical compression of the vasculature, and then they rapidly decline in response to decreases in cardiac output (Q̇) and venous return (VR). In the third phase, the decline in pressure ceases, and they may even progressively increase, as elevated sympathetic discharge raises total peripheral resistance (TPR). Once the strain is released and the intrathoracic vessels are no longer compressed, the pressure rapidly declines and often reaches its nadir. The final phase occurs immediately thereafter, in which there is a rapid overshoot in pressure above its baseline level as Q̇ and VR return to normal levels, while the TPR remains transiently elevated (41, 56). A progressive increase in HR throughout the period of strain is also expected, followed by bradycardia that occurs in response to both the strain release and baroreflexive reaction to the overshoot in pressure (3, 11, 41, 56). An example of typical HR and BP responses to the Valsalva test is shown in Fig. 3. The HRmax/HRmin, SBPunder, DBPunder, SBPover, and DBPover values were determined for the Valsalva test using the same calculations described in the previous section, except, of course, that the critical event for these calculations centered around Valsalva strain instead of standing. Additionally, the initial increases in both SBP (SBP1st peak) and DBP (DBP1st peak) were determined for this test using the following calculation: Once again, the pressure baseline mean was the mean pressure during the 20 s that preceded the test. The 1st peak pressure score was the highest pressure value achieved during Valsalva strain. Finally, following recommendations from a very recent study by Hilz et al. (25), we also determined the interval between the SBPover value and the point in which SBP had decreased by 90% of the difference between the SBPover and SBP baseline mean (90% SBPnorm).
All data were analyzed using statistical software (SPSS 23.0; Armonk, NY). Differences in the group demographic characteristics were determined using independent t-tests. Differences in resting HR and BP values, HRdiff, HRmax/HRmin, SBPunder, DBPunder, SBPover, DBPover, SBPstand mean, DBPstand mean, SBP1st peak, DBP1st peak, and 90% SBPnorm variables were determined using 2 (group: concussed or control) × 4 (time: acute, subacute, week 1, and week 2) mixed-factor ANOVAs and multivariate ANOVAs (MANOVAs). MANOVAs were used as often as possible (i.e., when analyzing SBP and DBP responses during each phase of the standing and Valsalva tests) in an attempt to minimize the total number of analyses and the risk of committing a type I error. Any significant MANOVA or ANOVA values were subjected to post hoc analysis using 2 (group: concussed or control) × 4 (time: acute, subacute, week 1, and week 2) mixed-factor ANOVAs and independent t-tests, respectively. Effect sizes were expressed using partial η2 (ηp2) for both the MANOVAs and ANOVAs and using Cohen’s d for the t-tests. All values are reported as means ± SD. Statistically significant values have a P value of <0.05.
As was expected from the inclusion and exclusion criteria (e.g., controls were excluded if they had had a concussion), the concussed participants had a significantly greater history of concussions than the controls, and there were no significant group differences with any of the anthropometric variables that were used to match the participants (Table 1). Among the 12 concussed participants, one-half had previously suffered at least one concussion (3 women and 3 men), and the other one-half had not. All participants denied suffering a concussion within the prior year, and those with a prior concussion were unable to accurately identify exact duration or date of injury.
Resting HR and BP.
For each trial, 30-s measures of HR, SBP, and DBP were taken between the 4th and 5th min of quiet resting in the supine position (Table 2). Those data were averaged and then analyzed using a mixed-factorial MANOVA. The interaction was significant (F9,13 = 2.92, P = 0.03, ηp2 = 0.67), and post hoc ANOVAs revealed there the source of the difference was the SBP (F3,63 = 3.22, P = 0.03, ηp2 = 0.13). Follow-up t-tests revealed that the concussed participants had significantly higher SBP during the acute measurement (t21 = 2.44, P = 0.02, d = 1.03).
Forced breathing test.
A mixed-factorial ANOVA analysis of the HRdiff scores indicated there was a significant interaction (F3,63 = 4.31, P = 0.01, ηp2 = 0.17). Although there was a relative decrease in concussed scores between the acute, subacute, week 1, and week 2 measurements (Table 3), follow-up t-tests did not reveal any significant differences with the control scores at any of those four times.
The results of all the MANOVAs and ANOVAs that were used to analyze the variables from this test are displayed in Table 4. A mixed-factorial ANOVA of the HRmax/HRmin scores indicated a significant interaction (F3,63 = 4.08, P = 0.01, ηp2 = 0.16). Post hoc tests revealed that the source of the interaction was during the acute measurement (t21 = 2.33, P = 0.03, d = 1.01), but the concussed scores fell to statistically similar levels with those of the controls during the subacute, week 1, and week 2 measurements (Table 5).
A mixed-factorial MANOVA revealed a significant interaction with the SBPunder and DBPunder scores (F6,16 = 2.59, P = 0.02, ηp2 = 0.11), and follow-up mixed-factorial ANOVAs indicated there were significant interactions with both SBP (F3,63 = 4.71, P = 0.00, ηp2 = 0.18) and DBP (F3,63 = 4.41, P = 0.01, ηp2 = 0.17). Follow-up t-tests indicated that the concussed group had significantly greater SBPunder scores (t21 = 2.98, P = 0.01, d = 1.24), and nearly significantly greater DBPunder scores (t21 = 1.81, P = 0.08), than the control group during the acute measurement (Table 5). Neither a second mixed-factorial MANOVA of the SBPover and DBPover scores nor one-third of the SBPstand mean and DBPstand mean scores yielded any significant results.
Table 6 lists the results of all of the MANOVAs and ANOVAs that were used to analyze data from this test. The only significant findings were associated with the mixed-factorial ANOVA that was used to evaluate the differences in the 90% SBPnorm time. There was a significant interaction (F3,60 = 3.45, P = 0.02, ηp2 = 0.14), and post hoc t-tests indicated the concussed group had a significantly greater normalization time during the acute measurement (t21 = 2.64, P = 0.02, d = 1.10) (Table 7).
This study sought to determine the effect of concussion on cardiovascular responses to three well-validated and highly reliable tests (3, 11, 41, 56) of autonomic function. The results indicate that concussion caused large acute increases in resting SBP, HR, and SBP perturbations during standing, as well as in 90% SBPnorm times following Valsalva-strain acutely (<48 h) postconcussion. Concussion also caused meaningful transient increases in both HR responses to forced breathing and DBP perturbations during standing. Given that one-half of the concussed participants’ had no previous history of concussions, that none of the concussed group’s previous concussions had occurred within 1 yr of this investigation, and that all of their observed abnormal HR and BP responses resolved within the 48–72 h of injury, it seems unlikely that those abnormalities were due to any chronic effects of concussion. Therefore, the evidence supports our hypothesis that concussion temporarily disrupts autonomic control of cardiovascular function in a manner that can be evaluated using standard autonomic reflex tests. To the best of our knowledge, this is the first investigation to have demonstrated concussion-induced abnormalities in both HR during forced breathing and BP during standing.
The HR abnormalities reported herein provide additional support to those studies that found excessive increases in HR with tilt-table testing (23, 26) and abnormal control of HR during various forms of exercise following concussion (1, 12, 13, 29). On the other hand, we did not find any evidence that concussion affected HR responses either to quiet resting in the supine position or to the Valsalva maneuver. The similarity in resting HR values between the concussed and control participants was less unexpected, as numerous studies have indicated that physical strain may be necessary to demonstrate the uncoupling of autonomic nervous and cardiovascular systems (12, 13, 29, 37). However, it is interesting and unclear why the strain induced by the standing and forced breathing tests was sufficient to disrupt the control of HR in the concussed participants, whereas the strain of the similarly effective Valsalva test of autonomic function apparently was not. It is important to point out that Valsalva tests of autonomic function are typically performed using a mouthpiece and at the precise pressure of 40 mmHg (11, 41, 56), whereas the participants in this investigation simply blew through a narrow hematocrit tube. They were instructed to blow as hard and as fast as possible for the full duration of the test, but it was not possible to measure or control the pressure they generated. Still, although TPR was not reported in this study, it was continuously monitored, and it typically increased two or three times above baseline levels throughout the Valsalva test, which indicates the technique did indeed result in significant strain. Additionally, the Valsalva HR and BP responses reported in this investigation (Fig. 3) were very similar to the typical responses reported by both Low and Sletten (41) and Wieling and Karemaker (56). The results were also very similar to those of Hilz et al. (25), and, although those investigators did not examine the acute effects of injury, they also found no evidence that mild traumatic brain injury (mTBI) affects the Valsalva HR ratio. Therefore, it seems more likely that the Valsalva HR ratio is not an effective means by which to assess abnormalities following concussion.
At least seven other published studies have examined the effect of brain injury on the arteries (32) and arterial pressure (17, 24, 25, 29, 34, 35), and all seven also found evidence of dysregulation. Of those studies, the two most relevant to this investigation both used similar autonomic reflex tests to demonstrate that patients who had previously suffered an mTBI had reduced cardiovascular modulation compared with healthy controls. The first study by Hilz et al. (24) found evidence of reduced arterial baroreceptor sensitivity in both supine and standing positions post-mTBI, and the second by Hilz et al. (25) observed baroreflex dysfunction and a delayed decrease in BP following a Valsalva maneuver. Those findings are comparable to, and may even help explain, the abnormal supine SBP, BP undershoot during standing, and Valsalva SBP normalization times observed in this investigation. However, despite other comparable results between the present study and that by Hilz et al. (25), such as finding no significant group differences in BP during any other phase of the Valsalva maneuver, there was an important discrepancy between the two studies. The most direct example of this discrepancy was with the 90% SBPnorm times following Valsalva strain, which is an indicator of the time required to withdraw baroreflex-mediated sympathetic control of BP. Compared with healthy controls, Hilz et al. (25) found significantly greater normalization times in mTBI patients several months to even years after injury, whereas the relatively longer times observed in the concussion group in the present study subsided just a few days after injury. It is possible this discrepancy was due to differences in Valsalva methodology and strain (described above). It may, therefore, be informative that the mean 90% SBPnorm times reported by Hilz et al. (25) were 16.9 and 12.6 s for the post-mTBI and healthy participants, respectively, whereas the comparable group mean values across all four measurements in this study were 8.6 and 7.1 s, respectively. A second explanation for the discrepancy could be differences in subject characteristics, as all of the injured participants in this investigation were recreationally active and below the age of 22 yr, while those studied by Hilz et al. (25) had a mean age of 35 yr and were likely less physically active. As those investigators noted, the autonomic cardiovascular dysfunction they observed may have been due to physical deconditioning after injury, and, although it is controversial, there is also some evidence that autonomic function declines with age (52). A third possibility is that at least some of the patients studied by Hilz et al. (25) had sustained minute disruptions in central autonomic pathways, and that fewer or none of the concussed participants in the present study did, but that possibility cannot be explored using the information provided and without neuroimaging techniques.
Concussion is known to disrupt many different areas of the brain (14, 15), including multiple areas associated with autonomic control of cardiovascular function and the efferent signals sent to the baroreceptors, cardiac pacemaker cells, and peripheral vessels (17). Given the complex nature of both concussive injury and the control of cardiovascular function, as well as individual physiological differences, it is not surprising that diverse, and in some cases conflicting, effects have been described concerning the uncoupling of SNS vs. PNS control. For example, many studies have found that concussion reduces HR variability (1, 12, 13, 17, 18, 36, 49, 50, 54), and those findings have generally been interpreted to indicate that SNS activity is upregulated by concussion (5, 12, 13, 28, 36). It is worth noting that those interpretations have been questioned (31) because they were based on changes in the low-frequency (LF) component of variability relative to the high-frequency (HF) component, which was understood to reflect changes in SNS innervation. However, recent evidence indicates that the LF component of HR variability reflects baroreflex function and not SNS innervation of the heart (10, 16, 46, 52). Still, Heyer et al. (23), Kanjwal et al. (26), and La Fountaine et al. (32) investigated variables other than HR variability and the LF/HF, and all three concluded that there was evidence of excessive SNS activity following concussion. By contrast, some studies provide evidence that mTBI can actually reduce SNS activity, including those that have investigated autonomic control of the pupillary light reflex (8), cardiovascular function during standing (24), and tilt-table testing (19). Others have identified vagal dysfunction as a major cause of the HR abnormalities that occur with concussion. For example, Abaji et al. (1) found that concussed athletes had significantly lower HF power bands leading to higher LF/HF, which indicated that excessive PNS withdrawal, and not altered SNS activity, contributed to the HR variability they observed. Also, La Fountaine (30) demonstrated that concussion caused temporary elevations in the QT interval variability index, which suggested an impairment of vagal activity. Returning to the measures investigated in this study, HR responses to forced breathing are typically under the control of the PNS, and BP is more associated with SNS control (3, 11, 41). Consequently, the observed abnormalities in HR and BP values indicate that concussion acutely reduced PNS activity and enhanced SNS activity, respectively, and so the results of this study agree with the two most common findings discussed above. More importantly, the results also provide indirect support to the conclusions of Hilz et al. (24, 25) that mTBI reduces baroreflex sensitivity and may indicate a greater cardiovascular risk.
Another indication of the complexity of concussive injury is the reportedly wide range of time in which the symptoms of CVAD persist. The abnormalities observed in this investigation were evident up to 48 h postinjury, but they resolved by 72 h postconcussion, which is similar to clinical screening of mental status and balance (43). This finding is roughly comparable to that of several other studies (30, 31, 50) of CVAD and the common observation that most individuals with a sport-related concussion recover within 7–10 days of injury (43). However, at least seven other investigations demonstrated that the symptoms of CVAD can last many weeks to months beyond that time frame (1, 23, 25, 29, 34, 35, 54). Most of those studies (1, 23, 29, 34, 35) did specifically investigate postconcussion syndrome (PCS), which means they recruited individuals who, by definition, exhibited symptoms of concussion for unusually long periods of time. While all participants herein recovered within typical time frames, reports indicate that as many as 15% (44) to one-third (4) of all concussed individuals develop PCS (4), and so future studies of CVAD may benefit by monitoring their participants well beyond the 2-wk time frame used in this investigation. It would also likely be useful to determine whether there is a link between the symptoms of CVAD and the more common symptoms of either concussion or PCS, such as headaches, visual dysfunction, depression, cervical injury, dizziness, insomnia, fatigue, cognitive impairments, etc.
The most significant limitation to this investigation was the small sample size. Given that limitation, it is important to explain that the a priori goal of this study was to recruit between 10 and 12 concussed participants, which was more than were used in many comparable studies (26, 30–32, 35), and that recruitment goal was informed by our expectations concerning our access to concussed individuals. In retrospect, those expectations were correct in the narrow sense that it took the investigators more than 2 yr to recruit the 12 concussed participants who participated in the study. That said, the evidence indicates that several of the analyses were considerably constrained by high coefficient of variation scores, most of which exceeded 50%, and by power values that were below the desired minimum of 0.8 (55). For example, the resting DBP interaction just missed statistical significance, despite having observed power values of 0.6. Nevertheless, the results of this investigation, along with those of similar studies (24, 25), indicate that there is a relationship between concussion and both HR and BP responses to the Valsalva maneuver and upright posture that warrant further investigation. It would be ideal if such studies could use tilt-table testing, rather than standing, to assess postural responses, because it is the more common (i.e., more effective) method used during clinical assessments of autonomic function (3, 11, 41, 56). Future similar studies should also consider monitoring HR and BP responses throughout other common clinical tests of autonomic function, such as the sustained handgrip and cold pressor tests.
Perspectives and Significance
Millions of Americans suffer sports-related concussions each year (33). Our study provides additional support to a growing body of evidence that concussive injury can temporarily disrupt autonomic control of cardiovascular function (e.g., Refs. 1, 23, 29, 32, 34, 54), and that this dysfunction may be an effective biomarker for concussion recovery (32). The novel element of the present study is that we used multiple standard clinical tests of autonomic function, and we demonstrated that concussion resulted in acute abnormalities in resting SBP, HR responses to both forced breathing and standing, and BP responses to both standing and the Valsalva maneuver. The time frame of dysfunction was consistent with the most substantial changes in the neurometabolic cascade, including elevated glutamate, potassium, and calcium during a time of reduced cerebral blood flow (14). While all current concussion guidelines recommend no return to participation on the day of injury, these results further support the progressive return to participation protocols, thus preventing individuals from returning to activities while experiencing autonomic dysfunction (44). The results also mirror the recovery time line of balance and cognitive testing following a concussion, which suggests autonomic impairment results from the concussion (43). These results expand the existing literature on autonomic dysfunction postconcussion and provide a foundation for future investigations that can utilize a within-subjects design incorporating baseline/premorbid data. The advantage of using autonomic tests, such as forced breathing, standing, and the Valsalva maneuver, is that they are highly reliable, valid, and noninvasive, and they require less physical exertion than most forms of exercise.
No conflicts of interest, financial or otherwise, are declared by the author(s).
J.L.D. and T.B. conceived and designed research; J.L.D., M.B.Y., J.P., and K.E. performed experiments; J.L.D., M.B.Y., J.P., K.E., and T.B. analyzed data; J.L.D. and T.B. interpreted results of experiments; J.L.D. prepared figures; J.L.D. and T.B. drafted manuscript; J.L.D., M.B.Y., J.P., and T.B. edited and revised manuscript; J.L.D., M.B.Y., J.P., K.E., and T.B. approved final version of manuscript.
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