During the past 20 years, significant advances in patient care have resulted in individuals with spinal cord injury (SCI) living longer than before. As lifespan increases, cardiovascular complications are emerging as the leading cause of mortality in this population, and individuals with SCI develop cardiovascular disease at younger ages than their able-bodied counterparts. To address this increasing clinical challenge, several recent studies investigated the central cardiovascular adaptations that occur following SCI. However, a somewhat less recognized component of cardiovascular dysfunction in this population is the peripheral vascular adaptations that also occur as a result of SCI. Literature review. To present a comprehensive overview of changes in arterial structure and function, which occur after SCI. Canada. A systematic literature review was conducted to extract studies that incorporated measures of arterial structure or function after SCI in animals or humans. Individuals with SCI exhibit vascular dysfunction below the lesion that is characterized by a reduction in conduit artery diameter and blood flow, increased shear rate and leg vascular resistance, and adrenoceptor hyper-responsiveness. There is also recent alarming evidence for central arterial stiffening in individuals with SCI. Although physical deconditioning is the primary candidate responsible for the maladaptive remodeling of the peripheral vasculature after SCI, there is emerging evidence that blood pressure oscillations, such as those occurring in the large majority of individuals with SCI, also exacerbates vascular dysfunction in this population.

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Peripheral vascular function in spinal cord injury: a systematic review

A spinal cord injury (SCI) interferes with the autonomic nervous system (ANS). The effect on the cardiovascular system will depend on the extent of damage to the spinal/central component of ANS. The cardiac changes are caused by loss of supraspinal sympathetic control and relatively increased parasympathetic cardiac control. Decreases in sympathetic activity result in heart rate and the arterial blood pressure changes, and may cause arrhythmias, in particular bradycardia, with the risk of cardiac arrest in those with cervical or high thoracic injuries. The objective of this review is to give an update of the current knowledge related to the alterations in cardiac autonomic control following SCI. With this purpose the review includes the following subheadings: 2. Neuro-anatomical plasticity and cardiac control 2.1 Autonomic nervous system and the heart 2.2 Alteration in autonomic control of the heart following spinal cord injury 3. Spinal shock and neurogenic shock 3.1 Pathophysiology of spinal shock 3.2 Pathophysiology of neurogenic shock 4. Autonomic dysreflexia 4.1 Pathophysiology of autonomic dysreflexia 4.2 Diagnosis of autonomic dysreflexia 5. Heart rate/electrocardiography following spinal cord injury 5.1 Acute phase 5.2 Chronic phase 6. Heart rate variability 6.1 Time domain analysis 6.2 Frequency domain analysis 6.3 QT-variability index 6.4 Nonlinear (fractal) indexes 7. Echocardiography 7.1 Changes in cardiac structure following spinal cord injury 7.2 Changes in cardiac function following spinal cord injury 8. International spinal cord injury cardiovascular basic data set and international standards to document the remaining autonomic function in spinal cord injury.

Alterations in cardiac autonomic control in spinal cord injury

Cardiovascular dysfunction following spinal cord injury

Trauma, hemorrhagic shock (T/HS), and subsequent multiple organ dysfunction syndrome (MODS) remain a current challenge in modern medicine. During trauma-hemorrhagic shock, intestinal injury and increased permeability leads to the generation of tissue injurious factors that are carried to the systemic circulation via the mesenteric lymphatics (1, 2). The gut has been shown to be a source of inflammatory factors with the capability of priming neutrophils and driving multiple organ failure after injury (3, 4), while gut protective strategies, involving both intraluminal and extraluminal modulators have demonstrated significant protection against the development of toxic post-shock mesenteric lymph and distant organ dysfunction (5–7). However, neural regulation via the vagus nerve, has been shown to be a critical component regulating normal intestinal function and intestinal defenses, the potentially protective effect of neuromodulation via stimulation of the vagus nerve on T/HS-induced gut injury and the production of biologically active mesenteric lymph has not been tested.

While neural regulation of gut injury has not been extensively studied, the vagus nerve represents the longest parasympathetic nerve connecting the central nervous system with the principal visceral organs. The classical function of the vagus nerve is to control heart rate, hormone secretion, as well as digestion and peristalsis in the gastrointestinal tract. Furthermore, the vagus nerve allows bidirectional communication between the brain and the immune system as well as the organs it innervates. By activating the sensory fibers of the vagus nerve, the immune and organ systems can send signals to the brain that in turn stimulate the efferent fibers of the vagus nerve to control the peripheral immune system as well as organ function. For example, the effector neurons in the vagus nerve can inhibit the production of pro-inflammatory cytokines from tissue macrophages (8). Likewise, the vagus nerve is thought to be involved in maintenance of the intestinal mucosal barrier function as reflected in intrinsic neural and central neural modulation of host defense activity in infectious colitis and other inflammatory diseases (9, 10).

In studies of endotoxemia, vagus nerve stimulation (VNS) was shown to decrease the systemic inflammatory response syndrome (SIRS) by attenuating the systemic inflammatory response to endotoxin (11). The pathway by which vagus nerve stimulation attenuates systemic inflammation after endotoxemia involved the spleen, because vagus nerve stimulation did not inhibits systemic inflammation in splenectomized mice (12). This pathway is termed the ‘cholinergic anti-inflammatory pathway’ because acetylcholine, the principle vagal neurotransmitter, inhibits the production of proinflammatory cytokines via the α7 nicotinic acetylcholine receptor subunit (α7nAChR) (8) as does nicotinic cholinergic agonists (13). Thus, from a clinical perspective, nicotine and other cholinergic agonists can potentially provide an alternative pharmacological strategy to mimic vagus nerve stimulation and to control systemic inflammation.

Based on studies showing VNS is protective in burn injury (14) as well as endotoxemia and bacterial infective models (8, 11, 12), we hypothesize that neuromodulation via vagal stimulation would be protective in our trauma-hemorrhagic shock model. Specifically, we hypothesize that vagus nerve stimulation will prevent gut barrier injury after trauma and hemorrhagic shock and therefore decrease the production of toxic mesenteric lymph thereby protecting the lung from injury. We examine whether the spleen is a necessary organ conferring protection in the vagus nerve stimulation model and, finally, whether a nicotinic agonist can mimic the protective effects of the vagus nerve.

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Parasympathetic stimulation via the vagus nerve prevents systemic organ dysfunction by abrogating gut injury and lymph toxicity in trauma and hemorrhagic shock.

Hagen EM, Faerestrand S, Hoff JM, Rekand T, Gronning M. Cardiovascular and urological dysfunction in spinal cord injury.
Acta Neurol Scand: 2011: 124 (Suppl. 191): 71–78.
© 2011 John Wiley & Sons A/S.

Objective –  A spinal cord injury (SCI) above the sixth thoracic vertebra interrupts the supraspinal control of the sympathetic nervous system causing an imbalance between the sympathetic and the parasympathetic nervous system. This article focuses on the symptoms, treatment and examination of autonomic disturbances of the cardiovascular and the urinary system after a SCI.

Methods –  A non-systematic literature search in the PubMed database.

Results –  Frequent complications in the acute phase of cervical and high thoracic SCI are bradyarrhythmias, hypotension, hypothermia/hyperthermia, increased neurogenic shock, vagovagal reflex, supraventricular/ventricular ectopic beats, vasodilatation and congestion. Serious complications in the chronic phase of SCI are orthostatic hypotension, impaired cardiovascular reflexes, autonomic dysreflexia (AD), reduced sensation of cardiac pain, loss of reflex cardiac acceleration, quadriplegic cardiac atrophy due to loss of left ventricular mass and pseudo-myocardial infarction. AD is associated with a sudden, uncontrolled sympathetic response, triggered by stimuli below the injury. It may cause mild symptoms like skin rash or slight headache, but also severe hypertension, cerebral haemorrhage and death. Early recognition and prompt treatment are important. Urinary autonomic dysfunctions include hyperreflexia or areflexia of detrusor and/or sphincter of the bladder.

Conclusions –  Patients with SCI have a high risk of cardiovascular complications, AD and urinary autonomic dysfunction both in the acute phase and later, affecting their prognosis and quality of life. Knowledge of cardiovascular and urological complications after SCI is important for proper diagnosis and treatment.

Cardiovascular and urological dysfunction in spinal cord injury.

The aim of this article is to analyze cardiac dysfunctions occurring after spinal cord injury (SCI). Cardiac dysfunctions are common complications following SCI. Cardiovascular disturbances are the leading causes of morbidity and mortality in both acute and chronic stages of SCI. We reviewed epidemiology of cardiac disturbances after SCI, and neuroanatomy and pathophysiology of autonomic nervous system, sympathetic and parasympathetic. SCI causes disruption of descendent pathways from central control centers to spinal sympathetic neurons, originating into intermediolateral nuclei of T1-L2 spinal cord segments. Loss of supraspinal control over sympathetic nervous system results in reduced overall sympathetic activity below the level of injury and unopposed parasympathetic outflow through intact vagal nerve. SCI associates significant cardiac dysfunction. Impairment of autonomic nervous control system, mostly in patients with cervical or high thoracic SCI, causes cardiac dysrrhythmias, especially bradycardia and, rarely, cardiac arrest, or tachyarrhytmias and hypotension. Specific complication dependent on the period of time after trauma like spinal shock and autonomic dysreflexia are also reviewed. Spinal shock occurs during the acute phase following SCI and is a transitory suspension of function and reflexes below the level of the injury. Neurogenic shock, part of spinal shock, consists of severe bradycardia and hypotension. Autonomic dysreflexia appears during the chronic phase, after spinal shock resolution, and it is a life-threatening syndrome of massive imbalanced reflex sympathetic discharge occurring in patients with SCI above the splanchnic sympathetic outflow (T5-T6). Besides all this, additional cardiac complications, such as cardiac deconditioning and coronary heart disease may also occur. Proper prophylaxis, including nonpharmacologic and pharmacological strategies and cardiac rehabilitation diminish occurrence of the cardiac dysfunction following SCI. Each type of cardiac disturbance requires specific treatment.

Rares Stoian

Papers

Cardiac dysfunctions following spinal cord injury