Effects of posttraumatic stress disorder on cardiovascular stress responses in Gulf War veterans with fatiguing illness

Abstract:

Abnormal cardiovascular stress responses have been reported in Gulf War veterans with chronic fatigue. However, many of these veterans also suffer from posttraumatic stress disorder (PTSD), which could potentially explain the reported abnormalities. To test this hypothesis, 55 Gulf veterans (GVs) with chronic fatigue syndrome (CFS) or idiopathic chronic fatigue (ICF) were stratified into groups with (N=16) and without (N=39) comorbid PTSD, and were compared to healthy Gulf veterans (N=47) on cardiovascular responses to a series of stressors.

The CFS/ICF with PTSD group had lower blood pressure responses to speech and arithmetic tasks, and more precipitous declines and slower recoveries in blood pressure after standing up than the controls. Similar trends in the CF/ICF group without PTSD were not significant, however. Both CFS/ICF groups had blunted increases in peripheral vascular resistance during mental tasks. However, only the veterans with comorbid PTSD had diminished cardiac output responses to the mental stressors and excessive vasodilatory responses to standing. Symptoms of posttraumatic stress were significant predictors of hypotensive postural responses, but only in veterans reporting a significant exposure to wartime stress.

We conclude that comorbid PTSD contributes to dysregulation of cardiovascular responses to mental and postural stressors in Gulf veterans with medically unexplained fatiguing illness, and may provide a physiological basis for increased somatic complaints in Gulf veterans with symptoms of posttraumatic stress.

 

Source: Peckerman A, Dahl K, Chemitiganti R, LaManca JJ, Ottenweller JE, Natelson BH. Effects of posttraumatic stress disorder on cardiovascular stress responses in Gulf War veterans with fatiguing illness. Auton Neurosci. 2003 Oct 31;108(1-2):63-72. http://www.ncbi.nlm.nih.gov/pubmed/14614966

 

Role of impaired lower-limb venous innervation in the pathogenesis of the chronic fatigue syndrome

Abstract:

BACKGROUND: In patients with acute orthostatic hypotension, there is excessive pooling of blood in the legs, which may result from the strikingly subnormal compliance that is demonstrable in the pedal veins during norepinephrine infusion. The common occurrence of delayed orthostatic hypotension and/or tachycardia in the chronic fatigue syndrome (CFS) led to the present studies of foot vein compliance in CFS patients with a linear variable differential transformer.

METHODS: Seven patients with CFS were compared with 7 age- and gender matched healthy control subjects in their blood pressure, heart-rate, and plasma norepinephrine responses to prolonged standing and in measurements of their foot vein contractile responses to intravenous norepinephrine infusions with the linear variable differential transformer.

RESULTS: Excessive, delayed (usually after 10 min) orthostatic reductions in systolic and diastolic blood pressure (P < 0.01) and inconsistently excessive increases in heart rate were found in the CFS patients, in whom venous compliance in response to infused norepinephrine was significantly reduced (P < 0.05).

CONCLUSIONS: In these patients with CFS, delayed orthostatic hypotension was clearly demonstrable, and, as in previously reported patients with orthostatic hypotension of acute onset, this was associated with reduced pedal vein compliance during norepinephrine infusion, implying impaired sympathetic innervation of foot veins. The rapid symptomatic improvement demonstrated in previous studies of CFS patients during correction of orthostatic venous pooling by inflation of military antishock trousers (MAST) to 35 mm Hg may suggest that excessive lower body venous pooling, perhaps by reducing cerebral perfusion, is involved in the orthostatic component of fatigue in these patients.

 

Source: Streeten DH. Role of impaired lower-limb venous innervation in the pathogenesis of the chronic fatigue syndrome. Am J Med Sci. 2001 Mar;321(3):163-7. http://www.ncbi.nlm.nih.gov/pubmed/11269790

 

Ruscus aculeatus (butcher’s broom) as a potential treatment for orthostatic hypotension, with a case report

Abstract:

CONTEXT: Chronic orthostatic hypotension (OH) is frequently a severely debilitating disease that affects large groups of the population with autonomic insufficiency–the elderly; patients with diabetes, Parkinson’s disease, and chronic fatigue syndrome; and anyone on drugs that affect the autonomic nervous system. Unfortunately, even though more than 60 medications are currently being used to treat OH, none of them is particularly or consistently effective. Ruscus aculeatus, a phytotherapeutic agent that is well known in Europe, may, however, change this. Its vasoconstrictive and venotonic properties make it ideally suited to treat the pooling of blood in the limbs, lack of venous tone, and lack of neurally mediated vasoconstriction that frequently characterize OH. Although it has never been suggested as a treatment for OH, it already has a long, proven record of use in Europe for treating a variety of circulatory disorders.

OBJECTIVE: To provide evidence for what appears to be an effective, safe, inexpensive botanical therapy for OH and encourage further studies on the efficacy of Ruscus for OH patients.

DESIGN: Review of OH and therapies currently available for OH and evaluation of the properties of Ruscus aculeatus, its mechanism of action, and its suitability as a therapeutic agent for treatment of OH.

RESULTS: A review of the many pharmacologic and nonpharmacologic agents for treating OH reveals that all of the drug therapies are disappointing and marginally useful. Although nonpharmacologic management is preferred, in the many cases in which OH becomes debilitating, pharmacologic intervention becomes a last resort. But drug therapy may not always be necessary, because Ruscus aculeatus, a phytotherapeutic agent containing ruscogenins and flavonoids, may prove useful for the treatment of OH if denervation is not so advanced that it has compromised receptor activity at the venous wall. Ruscus aculeatus is an alpha-adrenergic agonist that causes venous constriction by directly activating postjunctional alpha1- and alpha2-receptors, in turn stimulating the release of noradrenaline at the level of the vascular wall. It also possesses venotonic properties: it reduces venous capacity and pooling of blood in the legs and exerts protective effects on capillaries, the vascular endothelium, and smooth muscle. Its flavonoid content strengthens blood vessels, reduces capillary fragility, and helps maintain healthy circulation. Unlike most of the drug therapies used to treat OH, Ruscus aculeatus does not cause supine hypertension. It also appears to do something no other therapy can offer–alleviate the worsening effects of OH in environmentally hot conditions. Finally, it is an extremely safe, inexpensive, over-the-counter botanical medicine.

CONCLUSION: With proven phlebotherapeutic properties, including vasoconstrictive action and venotonic properties, Ruscus aculeatus shows great promise for ameliorating the symptoms of OH and improving the quality of life for large groups in the population. It clearly deserves to be the object of wider research and study as a treatment for OH.

 

Source: Redman DA. Ruscus aculeatus (butcher’s broom) as a potential treatment for orthostatic hypotension, with a case report. J Altern Complement Med. 2000 Dec;6(6):539-49. http://www.ncbi.nlm.nih.gov/pubmed/11152059

 

Autonomic neuropathies

Abstract:

A limited autonomic neuropathy may underlie some unusual clinical syndromes, including the postural tachycardia syndrome, pseudo-obstruction syndrome, heat intolerance, and perhaps chronic fatigue syndrome. Antibodies to autonomic structures are common in diabetes, but their specificity is unknown. The presence of autonomic failure worsens prognosis in the diabetic state. Some autonomic neuropathies are treatable. Familial amyloid polyneuropathy may respond to liver transplantation. There are anecdotal reports of acute panautonomic neuropathy responding to intravenous gamma globulin. Orthostatic hypotension may respond to erythropoietin or midodrine.

 

Source: Low PA. Autonomic neuropathies. Curr Opin Neurol. 1998 Oct;11(5):531-7. http://www.ncbi.nlm.nih.gov/pubmed/9848003

 

The role of delayed orthostatic hypotension in the pathogenesis of chronic fatigue

Abstract:

Past studies have shown that severe fatigue was the presenting symptom in six of seven patients with delayed orthostatic hypotension and that tilt table-induced hypotension was found in 22 of 23 patients with the chronic fatigue syndrome. We have determined the prevalence of fatigue, volunteered in response to a nonspecific pre-examination questionnaire used in 431 patients, each subsequently diagnosed as having one of eight neurological or endocrine disorders.

The results show that fatigue is a very common symptom in patients with delayed orthostatic hypotension (n = 21), as well as both primary (n = 30) and secondary (n = 106) hypocortisolism: 70-83% in all groups. In contrast, fatigue was an uncommon complaint in patients with multiple system atrophy (MSA) (n = 30), pituitary disorders without hypocortisolism (n = 106) or idiopathic hirsutism (n = 96): 7-33% in all groups, and was intermediate in prevalence in patients with acute hyperadrenergic orthostatic hypotension (n = 32): 41%.

It is concluded that fatigue commonly results from delayed orthostatic hypotension and all forms of hypocortisolism but is less common in patients with acute orthostatic hypotension, both idiopathic and due to MSA, which more commonly present with lightheadedness or syncope.

 

Source: Streeten DH, Anderson GH Jr. The role of delayed orthostatic hypotension in the pathogenesis of chronic fatigue. Clin Auton Res. 1998 Apr;8(2):119-24. http://www.ncbi.nlm.nih.gov/pubmed/9613802

 

Pathogenesis and management of delayed orthostatic hypotension in patients with chronic fatigue syndrome

Abstract:

The relationship between orthostatic hypotension and chronic fatigue syndrome (CFS) has been reported previously. To study the pathogenesis and management of delayed orthostatic hypotension in patients with CFS, a case comparison study with follow-up of 8 weeks has been designed.

A group of 78 patients with CFS (mean age 40 years; 49% men and 51% women), who fulfilled the Centre for Disease Control and Prevention criteria were studied. There were 38 healthy controls (mean age 43 years; 47% men and 53% women).

At entry to the study each subject underwent an upright tilt-table test, and clinical and laboratory evaluation. Patients with orthostatic hypotension were offered therapy with sodium chloride (1200 mg) in a sustained-release formulation for 3 weeks, prior to resubmission to the tilt-table testing, and clinical and laboratory evaluation.

An abnormal response to upright tilt was observed in 22 of 78 patients with CFS. After sodium chloride therapy for 8 weeks, tilt-table testing was repeated on the 22 patients with an abnormal response at baseline. Of these 22 patients, 10 redeveloped orthostatic hypotension, while 11 did not show an abnormal response to the test and reported an improvement of CFS symptoms.

However, those CFS patients who again developed an abnormal response to tilt-test had a significantly reduced plasma renin activity (0.79 pmol/ml per h) compared both with healthy controls (1.29 pmol/ml per h) and with those 11 chronic fatigue patients (1.0 pmol/ml per h) who improved after sodium chloride therapy (p = 0.04).

In conclusion, in our study CFS patients who did not respond to sodium chloride therapy were found to have low plasma renin activity. In these patients an abnormal renin-angiotensin-aldosterone system could explain the pathogenesis of orthostatic hypotension and the abnormal response to treatment.

 

Source: De Lorenzo F, Hargreaves J, Kakkar VV. Pathogenesis and management of delayed orthostatic hypotension in patients with chronic fatigue syndrome. Clin Auton Res. 1997 Aug;7(4):185-90. http://www.ncbi.nlm.nih.gov/pubmed/9292244