16 Key Points 1. In addition to motor and sensory deficits, individuals with spinal cord injury (SCI) face lifelong abnormalities in blood pressure control. 2. The acute period of cervical and upper thoracic SCI commonly presents with hypotension and bradycardia, a condition known as neurogenic shock. 3. As neurogenic shock resolves, unpredictable episodes of life-threatening hypertension, known as autonomic dysreflexia, could occur and will require prompt management. 4. In general, individuals with SCI have low resting arterial blood pressure. They also experience episodes of extremely low blood pressure when they are transferred to a wheelchair or attempt to stand up, a condition known as orthostatic hypotension. 5. Individuals with SCI at or above the sixth thoracic segment are at greater risk for abnormal cardiovascular control and the development of autonomic dysreflexia. Paralysis and loss of sensation are the most recognized consequences that occur following spinal cord injury (SCI). Young and healthy individuals are the most common victims of this devastating condition. Injury to the fragile neuronal structures in the spinal cord results not only in devastating paralysis in these individuals but also in significant functional alterations of the autonomic nervous system (ANS).1 Although the injury itself generally affects only a few segments of the spinal cord, the effect of this local disruption can commonly be seen in all autonomic functions below the level of injury, including bladder, bowel, respiration, temperature regulation, sexual function, and, most crucially for initial survival, cardiovascular control. From the moment of the injury, on a daily basis, individuals with SCI even following completion of rehabilitation face the challenge of their unstable blood pressure, which frequently results in persistent hypotension or episodes of uncontrolled hypertension.2 Immediately following injury there is hypotension with bradycardia, a typical manifestation of neurogenic shock.2 This condition is usually more pronounced with cervical injuries, lasts up to 6 weeks, and requires monitoring and management within the intensive care unit setting. With initial mobilization of subjects with SCI, orthostatic hypotension commonly becomes a significant issue.3 With reconditioning, the symptoms of orthostatic hypotension will subside in many subjects; however, some patients will have lifelong orthostatic intolerance. Opposite to orthostatic hypotension, individuals with injuries above six thoracic segments could experience significant episodes of hypertension known as autonomic dysreflexia.4 These episodes of unpredictable hypertension could initially occur in early stages following SCI and, if not managed promptly, could be life threatening. These cardiovascular abnormalities have been well documented in human studies, as well as in animal models. The recognition and management of these cardiovascular dysfunctions following SCI represent challenging clinical issues.5 Moreover, the latest clinical observations suggest that cardiovascular disorders are among the most common causes of morbidity and mortality in individuals with SCI.6 Until recently, the majority of basic science and clinical investigations were focused on finding a cure for paralysis and reestablishing motor function. Unfortunately, little attention has been paid to the function of the ANS following SCI. This chapter focuses on the range of clinical issues associated with abnormal cardiovascular control following SCI. Cardiovascular functions depend on coordinated neural control from the sympathetic and parasympathetic components of the ANS. Peripheral blood vessels receive predominantly sympathetic innervations, whereas the heart has dual sympathetic and parasympathetic innervations (Table 16.1). Supraspinal neurons within the rotroventralateral medulla (RVLM) and the sympathetic preganglionic neurons (SPNs) within the spinal cord are responsible for the tonic sympathetic control of the vessels and the heart. Cell bodies of SPNs are located within the lateral horns of the spinal gray matter of the thoracic and upper lumbar spinal segments (T1–L2, Fig. 16.1). These neurons receive supraspinal tonic and inhibitory nervous system control via spinal autonomic pathways—pathways that are commonly disrupted following SCI.7 Conversely, vagal (CN X) parasympathetic pathways, which exit supraspinally, are generally intact in individuals with SCI. As a result of the anatomical structure of the ANS, the level of SCI has important consequences for the autonomic dysfunctions observed after injury. Cardiac function, for example, is under dual control of sympathetic (SPNs from T1–5 levels) and parasympathetic (vagus, CN X) nervous systems (Fig. 16.1). Following high cervical SCI, parasympathetic (vagal) control will remain intact, whereas the sympathetic nervous system will lose its tonic autonomic control. On the other hand, in individuals with injury below the sixth thoracic segment, both the sympathetic and parasympathetic control of the heart are intact. As a result of injury level, individuals with tetraplegia versus those with paraplegia will have very different cardiovascular responses to injury.3,8 It is important to appreciate that similar relationships can exist between the level of SCI and function of organs that are under autonomic control (lungs, urinary bladder, bowel, sweat glands, etc.). Table 16.1 Autonomic Innervations of the Cardiovascular System
Autonomic Dysreflexia and Cardiovascular Complications of Spinal Cord Injury
Neural Control of the Cardiovascular System
Target organ | Sympathetic (adrenergic) | Parasympathetic (cholinergic) |
Heart |
|
|
Cardiac muscle | β1 and β2: increase in contractility | M2: decrease in contractility |
Sinoatrial (SA) node | β1 and β2: increase in heart rate | M2: decrease in heart rate |
Atrioventricular (AV) node | β1: increase in conduction | M2: decrease in conduction |
Blood vessels |
|
|
Smooth muscles of blood vessel (arteries/veins) | α1: vessel contraction | M3: vessel dilation *arteries of the cavernous tissue (erectile tissue) also have parasympathetic innervations |
*Indicates aberration or exception to the rule.
Fig. 16.1 Schematic diagram of autonomic control of cardiovascular systems and possible cardiovascular outcomes following spinal cord injury. The cerebral cortex and hypothalamus provide excitatory and inhibitory inputs to the various nuclei within the medulla oblongata involved in cardiovascular control. The parasympathetic control of the heart exits at the level of the brain stem via the vagus nerve (CN X). The preganglionic fibers of the vagus nerve then synapse with postganglionic parasympathetic neurons in ganglia on or near the target organ. Descending sympathetic input from the rostroventralateral medulla (RVLM) provide tonic control to spinal sympathetic preganglionic neurons (SPNs) involved in cardiovascular control. SPNs are found within the lateral horn of the spinal cord in segments T1–L2 and exit the spinal cord via the ventral root. They then synapse with postganglionic neurons located in the sympathetic chain (paravertebral ganglia). Finally, the sympathetic postganglionic neurons synapse with the target organs (heart and blood vessels). Afferent feedback for cardiovascular control from the central and peripheral baroreceptors is not shown.
Acute Postinjury Period and Neurogenic Shock
In the acute period, especially with injury at the cervical level, patients present clinically with severe hypotension and persistent bradycardia. This phenomenon is known as neurogenic shock.1 Clinical observations strongly suggest that the extent to which prolonged and severe hypotension requiring vasopressive therapy correlates well with the severity of the SCI, with cervical or high thoracic injury, and can last up to 5 weeks after injury.9 In one study, Glenn and Bergman reported that severe hypotension was present in all 31 tetraplegic subjects assessed with severe SCI, half of whom required pressor therapy to maintain arterial blood pressure.10 In addition to this pronounced hypotension, many patients with acute SCI experience severe abnormalities in heart rate. In the acute postinjury stage, bradycardia has been reported in between 64 and 77% of patients with cervical SCI, with the most severe and frequent episodes within the first 5 weeks.11 Bradycardia is a less severe problem when the injury is in the upper thoracic spinal cord because cardiac sympathetic neurons remain under brain stem control, leaving vagal and sympathetic influences more in balance. Both the level and the completeness of injury are important determinants of bradycardia severity. Indeed, we have also shown that the initial hypotension and bradycardia observed after injury persisted in the individuals with more severe injury of the descending cardiovascular autonomic pathways.7 More-over, all individuals in this group required vasopressor therapy to maintain systolic arterial blood pressure above 90 mmHg.12 In contrast, individuals with less severe injury to the descending cardiovascular pathways tended to have higher blood pressure and heart rate, although minor and short-term hypotension and low heart rates were occasionally observed.
In addition to neurogenic shock, the acute phase of SCI is also associated with “spinal shock.”13 Although some authors use these terms interchangeably, it is important to recognize that they are two clinically important and distinct conditions. Neurogenic shock is characterized by changes in autonomic blood pressure control following SCI, whereas spinal shock is characterized by a marked reduction or abolition of sensory, motor, and reflex function of the spinal cord below the level of injury.13 Clinically, spinal shock is characterized by flaccid paralysis and areflexia.
Autonomic Dysreflexia
Following the recovery from the neurogenic shock, resting hypotension is common among the majority of individuals with high thoracic and cervical SCI. However, the majority of these individuals could also experience episodes of pronounced hypertension (systolic blood pressure up to 300 mmHg), known as autonomic dysreflexia (AD) (Fig. 16.2). These episodes are triggered by painful or nonpainful sensory stimulation below the level of SCI, such as a full bladder or bowel. This condition is reported to occur in 50 to 90% of people with cervical and high thoracic SCI14 and generally occurs in individuals with SCI at or above T6, below which the main sympathetic outflow exits the spinal cord. We have found that AD can occur in the acute phase of SCI as early as 4 days after severe cervical injury.15 Although this possibility should always be considered in the clinical setting, it remains the case that AD typically develops over time after SCI. Cardiovascular dysfunction, including AD, increases with the level and severity of injury.16 Even among complete tetraplegics, the clinical presentation of AD is variable and ranges from uncomfortable symptoms to life-threatening crises.17,18 In a recent survey of people with SCI, the elimination of AD was identified by both paraplegics and tetraplegics as a high priority in improving their quality of life.19 Despite the clinical significance of abnormal cardiovascular control and AD following SCI, the factors that underlie this condition are still under discussion among clinical and basic scientists. SCI research has focused heavily on paralysis, and cardiovascular control and autonomic dysfunction have been generally neglected by both the clinical and research communities.
Fig. 16.2 Cardiovascular responses to vibrostimulation in a male with spinal cord injury (SCI). (A) Case of autonomic dysreflexia in a male with cervical SCI (C7 AIS B according to the American Spinal Injury Association Impairment Scale, motor complete, sensory incomplete) during the vibrostimulation (VS) procedure for sperm retrieval. Blood pressure (BP), obtained via finger cuff, and three-lead electrocardiography (ECG) were recorded continuously during the procedure. BP (top diagram) during the procedure and a 10 second sample of ECG recorded at the time of ejaculation (bottom diagram) are shown. Prior to VS there was relative hypotension (100/65 mmHg) with a regular heart rate of 78 bpm. With initiation of VS there was a gradual increase in arterial blood pressure suggestive of a typical episode of AD. Finally, at the time of ejaculation arterial BP surged to 280/150 mmHg, accompanied by bradycardia (38 bpm) and a short run of premature ventricular contractions (PVCs, indicated by the asterisk on the blood pressure recording) was observed 3 minutes following ejaculation (ECG recording at the bottom). At 15 minutes following ejaculation, arterial BP was still slightly elevated (130 mmHg, heart rate 66 bpm). During the next 30 to 35 minutes, arterial BP and heart rate gradually returned to resting values. This episode of AD was accompanied by significant spasms in the upper and lower extremities, profuse sweating on the forehead and neck, and piloerection on the forearms. Interestingly, during this episode of AD, the patient reported only a mild headache (personal observations). (B) Case of orthostatic hypotension in an individual with cervical C8 AIS A SCI during the orthostatic testing (sit-up test). Instrumentation for BP and ECG was conducted using the same settings as in (A). Supine resting arterial BP was measured as 95/65 mmHg, with heart rate of 74 bpm. Following passive sit-up (arrow) the arterial BP decreased and at 3 minutes of seating was measured at 70/55 mmHg with heart rate of 90 bpm. The patient also complained of slight dizziness. During the next 10 minutes of monitoring, arterial BP continued to be low, and the test was stopped due to increased dizziness and light-headedness (personal observations).
The majority of episodes of AD are self-limited or even asymptomatic (or “silent”) for individuals with chronic SCI.20,21 Most episodes of AD are easily managed by the individual with SCI or by a caregiver, by eliminating the inciting stimulus (i.e., via bladder emptying, bowel evacuation, change in position, or other measures4). However, it is also common that episodes of AD require pharmacological interventions or urgent hospitalization due to malignant presentation.22 A major concern with the repetitive and significant blood pressure elevation in AD (which distinguishes these hypertensive episodes in individuals with SCI from hypertension in able-bodied individuals) is a possible shear injury to the blood vessel endothelium that could pre-dispose these individuals to cardiovascular complications in the future.23
The mechanisms underlying the development of AD are still poorly understood. However, there are some experimental animal and clinical data suggesting that autonomic instability is a main contributing factor in the development of this condition. As described earlier in this chapter, changes occurring within the spinal autonomic circuits in both the acute and chronic stages following SCI have been identified among the possible causes of the AD.14
It is important to note, however, that, although AD occurs more often in the chronic stage of SCI at or above the sixth thoracic segment, there is clinical evidence of early episodes of AD in the first days and weeks after the injury.15,24 In fact, it seems likely that AD is underrecognized in the acute phase of SCI.15 It is also worth mentioning that despite the fact that AD is unpleasant22 and a life-threatening emergency,17 some wheelchair athletes with SCI voluntarily induce it before the competition to enhance their performance.25 Self-induced AD is commonly referred to as “boosting,” and it is considered un-ethical and illegal by the International Paralympics Committee Medical Commissions. Therefore, Paralympians are subject to medical examination before the competitions.
Orthostatic Hypotension
In addition to dramatic elevations in blood pressure due to episodes of AD, many individuals with SCI also experience episodes of extremely low blood pressure when they are transferred to a wheelchair or attempt to stand up. This is referred to as orthostatic hypotension (OH), and it is particularly common in the acute phase of injury.26 The Consensus Committee of the American Autonomic Society and the American Academy of Neurology define OH as a decrease in systolic blood pressure of 20 mmHg or more, or in diastolic blood pressure of 10 mmHg or more, upon the assumption of an upright posture from a supine position, regardless of whether symptoms occur.27 The symptoms of OH in individuals with SCI are similar to those in able-bodied individuals28 and include fatigue or weakness, light-headedness, dizziness, blurred vision, dyspnea, and restlessness.29,30 However, OH can also be asymptomatic; Illman and colleagues reported that 41.1% of cord-injured individuals who developed OH were asymptomatic, despite significant blood pressure falls.31 In a recent study from our laboratory, we also found that OH could persist asymptomatically in the chronic stage of SCI, despite a marked decrease in arterial blood pressure.32 In this study, blood pressure decreases indicative of OH were observed in 7/14 (50%) of cervical SCI subjects, and 2/11 (18%) of thoracic SCI subjects. Symptomatic OH was present in five (36%) cervical SCI subjects and two (18%) thoracic SCI subjects and required early termination of the test in two cervical SCI subjects.32 Asymptomatic OH is also reported in other able-bodied populations with autonomic disturbances and is likely a result of protective alterations in cerebral autoregulation despite cerebral hypoperfusion.33–35
Concerning the incidence and prevalence of OH in this population, orthostatic maneuvers performed during physiotherapy and mobilization are reported to induce blood pressure changes, diagnostic of OH, in 74% of cord-injured individuals, suggesting that OH is a common phenomenon among the cord-injured population.31
Several mechanisms have been proposed for the development of OH in the SCI population. Interruption of sympathoexcitatory efferent pathways from the brain stem to the spinal SPNs involved in vasoconstriction causes failure of short-term-reflex blood pressure regulation.36 This leads to pooling of blood in the viscera and dependent vasculature below the level of injury. Resting catecholamine levels are also lower in individuals with cervical SCI compared with those with paraplegia and able-bodied individuals, and there is no significant increase in epinephrine or norepinephrine levels when quadriplegic individuals undergo a head-up tilt.3 Individuals with SCI are also reported to have impaired baroreflex function,37 smaller plasma volumes due to hyponatremia,30 and possible cardiovascular deconditioning, at least in the early period following SCI, due to prolonged periods of bed rest.38 Any combination of these factors can further increase the likelihood and severity of OH. On the other hand, there are several changes that occur after SCI that can mitigate the severity of OH, including the recovery of spinal sympathetic reflexes, development of spasticity and increased muscle tone, and changes in the reninangiotensin system. While these changes have the potential to reduce the severity of OH, the reality is that OH remains a significant problem for the majority of the SCI population.
Deconditioning and Cardiovascular Control Following Spinal Cord Injury
A possible contributor to the high cardiovascular morbidity and mortality among individuals with SCI is a decreased ability to exercise and the resulting deconditioning.39,40 There is strong evidence from the able-bodied population that physical inactivity is associated with cardiovascular morbidity and mortality.41 The age-adjusted 2-year incidence of heart disease in the Canadian population is less than 1% for moderately active people and 2.3% for their sedentary counterparts. There is also evidence from the able-bodied population of an inverse relationship between the weekly amount of physical activity and both incidence of and mortality due to all cardiovascular disease.42 Although exercise, including passive movement of the paralyzed limbs, is routinely used in clinical practice, there are few data to describe how exercise affects the cardiovascular outcome of SCI. Our own clinical data indicate that locomotor training (i.e., weight-supported movement on a tread-mill) ameliorates cardiovascular control in SCI.43
Both short-term inactivity due to bed rest44 and long-term inactivity due to paralysis following SCI45,46 result in vascular adaptations in the inactive and paralyzed muscles, including reduced vessel diameter, decreased blood flow, increased shear stress, increased peripheral resistance, and decreased arterial compliance. In able-bodied populations, decreased central arterial compliance is associated with the incidence and progression of cardiovascular diseases.47 However, it is important to recognize that even structural alterations due to inactivity can be ameliorated with regular physical activity both in able-bodied individuals and in individuals with SCI.48,49 For example, regular endurance exercise improves endothelial function and arterial compliance in able-bodied individuals.50 Both animal data51 and recent clinical evidence52 suggest that vascular adaptations occur within days or weeks of the onset of training. There are only a few studies examining whether the vascular changes following SCI are reversible by training, and what the time course of these training-induced vascular adaptations might be.53,54 Our recent study evaluated compliance in large and small arteries before and after a 2-week training program using functional electrical stimulation leg cycle ergometry (FES-LCE).54 It appears that FES-LCE is effective in improving small-artery compliance in females with SCI.
Evaluation of Autonomic Functions Following Spinal Cord Injury
Until recently, the impact of an SCI on a person’s neurological function was evaluated through the use of only motor and sensory assessment that is a part of the International Standards for the Neurological Classification of Spinal Cord Injury. This assessment does not examine the status of autonomic dysfunctions in persons with SCI. Recently, the American Spinal Injury Association (ASIA) and the International Spinal Cord Society (ISCoS) proposed the strategy to document remaining autonomic neurological function following SCI.55 It has to be recognized that the complexity of organization of the ANS and its involvement in the control of almost every bodily system make it difficult to select appropriate clinical tests for individuals with SCI. The proposed autonomic classification system includes four components: general autonomic, bladder, bowel, and sexual functions (Fig. 16.3). The general autonomic component of the classification chart includes evaluation of cardiovascular dysfunction in individuals with SCI.
Conclusion
In addition to motor and sensory deficits, individuals with SCI face lifelong abnormalities in blood pressure control.14,56 The severity of these cardiovascular dysfunctions is affected by both the level and the completeness of injury to spinal autonomic pathways. Clinical evidence suggests that individuals with SCI on a daily basis can experience severe episodes of hypertension (known as AD)4 and, conversely, marked falls in blood pressure during positional change (OH).36 The long-term impact of dramatic blood pressure oscillations on vascular structure in the SCI population is unknown. However, one recent study indicates that carotid intima-media thickness is increased in individuals with SCI.57 Hypertensive crises can be life threatening and can result in seizures,58 myocardial ischemia,59 cerebral vascular accident,18 and death.17 Furthermore, individuals with SCI have an increased risk of developing heart disease and stroke, and cardiovascular dysfunction is one of the leading causes of death for people with SCI.6 Both AD and OH are known to prevent and delay rehabilitation and significantly impair the overall quality of life of individuals with SCI.22,31 Therefore, early recognition and timely management of cardiovascular dysfunctions in this population are crucial.
Related posts:
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Posttraumatic Syringomyelia: Pathophysiology and Management
Glial Scar and Monocyte-Derived Macrophages Are Needed for Spinal Cord Repair: Timing, Location, and Level as Critical Factors
The Human Central Pattern Generator and Its Role in Spinal Cord Injury Recovery
Somatosensory Function and Recovery after Spinal Cord Injury: Advanced Assessment of Segmental Sensory Function
Considerations for the Initiation and Conduct of Spinal Cord Injury Clinical Trials
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