Research in Review

• A new wrinkle: Skin manifestations of aging may relate to autonomic dysfunction
• Poll with DINET members
• Patterns of hypocapnia on tilt in patients with fibromyalgia, chronic fatigue syndrome, nonspecific dizziness, and neurally mediated syncope
• Anaesthetic management of a parturient with the postural orthostatic tachycardia syndrome: a case report
• Postural orthostatic tachycardia syndrome: Dental treatment considerations
• Clonidine for the treatment of supine hypertension and pressure natriuresis in autonomic failure
• Sodium Paradoxically Reduces the Gastropressor Response in Patients With Orthostatic Hypotension
• Increased plasma angiotensin II in postural tachycardia syndrome (POTS) is related to reduced blood flow and blood volume
• Postural Hypocapnic Hyperventilation is Associated with Enhanced Peripheral Vasoconstriction in Postural Tachycardia Syndrome with Normal Supine Blood Flow

A new wrinkle: Skin manifestations of aging may relate to autonomic dysfunction.

Bazar KA, Doux JD, Yun AJ.

Stanford University, 470 University Avenue, Palo Alto, CA 94301, United States.

Various mechanisms have been argued for skin wrinkling, one of the hallmarks of aging. We hypothesize that chronic sympathetic bias is a previously unrecognized mechanism for wrinkling. In the acute setting of water immersion, reversible skin wrinkling is a well-known reflex mediated by the autonomic nervous system. We postulate that skin wrinkling results as a local maladaptive manifestation of a global chronic sympathetic bias that emerges during aging. The persistence of such changes may induce additional compensatory remodeling to cause permanent alteration of the skin. Sympatholytic agents may prove beneficial for arresting or ameliorating the development of wrinkles. Conditions that amplify sympathetic bias such as stress, smoking, amphetamine abuse, HIV, heart failure, and transplantation may accelerate wrinkling. Other common diseases of the skin may also arise as particular manifestations of aberrant autonomic activity through induction of vascular and immune dysfunctions. The temporal and spatial distribution of these dermatologic conditions may reflect variation of autonomic balance, which also regulates T helper immune balance. For all of these dermatologic conditions, local and systemic administration of drugs and medical devices that pharmacologically or electrically modulate autonomic nervous system activity may yield benefits as well.

PMID: 16766136

Could the conclusions drawn in the above abstract reflect the experiences of our members with POTS? Here is what they had to say:

How old do you look?
I  have POTS with Ehlers-Danlos syndrome and People think I am around my age [ 5 ]  [19.23%] People think I am older than my age [ 2 ]  [7.69%] People think I am younger than my age [ 19 ]  [73.08%]
Total Votes: 26

People who do not have EDS, but do have POTS
I have POTS without Ehlers-Danlos syndrome and People say I look older than my age [ 2 ]  [5.56%] People say I look around my age [ 5 ]  [13.89%] People say I look younger than my age [ 29 ]  [80.56%]
Total Votes: 36

Am J Med Sci. 2006 Jun;331(6):295-303.

Patterns of hypocapnia on tilt in patients with fibromyalgia, chronic fatigue syndrome, nonspecific dizziness, and neurally mediated syncope.

Naschitz JE, Mussafia-Priselac R, Kovalev Y, Zaigraykin N, Slobodin G, Elias N, Rosner I.

From the Departments of Internal Medicine A (jen, rm-p, yk, nz, ne) and Rheumatology (ir), the Bnai-Zion Medical Center and Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.

OBJECTIVES: To assess whether head-up tilt-induced hyperventilation is seen more often in patients with chronic fatigue syndrome (CFS), fibromyalgia, dizziness, or neurally mediated syncope (NMS) as compared to healthy subjects or those with familial Mediterranean fever (FMF).

PATIENTS AND METHODS: A total of 585 patients were assessed with a 10-minute supine, 30-minute head-up tilt test combined with capnography. Experimental groups included CFS (n = 90), non-CFS fatigue (n = 50), fibromyalgia (n = 70), nonspecific dizziness (n = 75), and NMS (n =160); control groups were FMF (n = 90) and healthy (n = 50). Hypocapnia, the objective measure of hyperventilation, was diagnosed when end-tidal pressure of CO2 (PETCO2) less than 30 mm Hg was recorded consecutively for 10 minutes or longer. When tilting was discontinued because of syncope, one PETCO2 measurement of 25 or less was accepted as hyperventilation.

RESULTS: Hypocapnia was diagnosed on tilt test in 9% to 27% of patients with fibromyalgia, CFS, dizziness, and NMS versus 0% to 2% of control subjects. Three patterns of hypocapnia were recognized: supine hypocapnia (n = 14), sustained hypocapnia on tilt (n = 76), and mixed hypotensive-hypocapnic events (n = 80). Hypocapnia associated with postural tachycardia syndrome (POTS) occurred in 8 of 41 patients.

CONCLUSIONS: Hyperventilation appears to be the major abnormal response to postural challenge in sustained hypocapnia but possibly merely an epiphenomenon in hypotensive-hypocapnic events. Our study does not support an essential role for hypocapnia in NMS or in postural symptoms associated with POTS. Because unrecognized hypocapnia is common in CFS, fibromyalgia, and nonspecific dizziness, capnography should be a part of the evaluation of patients with such conditions.

PMID: 16775435

Br J Anaesth. 2006 May 12;

Anaesthetic management of a parturient with the postural orthostatic tachycardia syndrome: a case report.

Corbett WL, Reiter CM, Schultz JR, Kanter RJ, Habib AS.

Department of Anaesthesiology, Box 3094, USA.

Postural orthostatic tachycardia syndrome encompasses a group of disorders characterized by orthostatic intolerance. We describe the anaesthetic management of analgesia for labour and of Caesarean section in a parturient suffering from this disorder. Worsening of her symptoms during pregnancy was managed with an increase in the dose of beta-blockers taken by the patient. Epidural analgesia was instigated early to attenuate the stress of labour and avoid consequent triggering of a tachycardic response. Slow titration of epidural analgesia and anaesthesia after an adequate fluid preload was undertaken to minimize hypotension and subsequent tachycardia. Neuraxial opioid, combined with non-steroidal anti-inflammatory drugs and bilateral iliohypogastric and ilioinguinal nerve blocks were used to optimize postoperative analgesia.

PMID: 16698864

J Am Dent Assoc. 2006 Apr;137(4):488-93.

Postural orthostatic tachycardia syndrome: Dental treatment considerations.

Brooks JK, Francis LA.

Department of Diagnostic Sciences and Pathology, Baltimore College of Dental Surgery, Dental School, University of Maryland, Baltimore, MD 21201, USA. Oralpath5@aol.com

BACKGROUND: Postural orthostatic tachycardia syndrome (POTS) is a chronic, relatively common autonomic disorder typically affecting younger females. It is distinguished by a dramatic increase in heart rate on the assumption of an upright posture from the supine position.

METHODS: The authors provide an overview of the demographics, clinical assessment, diagnostic features, differential diagnoses, pathogeneses and medical treatment of patients with POTS, with an emphasis on the clinical treatment of the dental patient affected by the syndrome.

CONCLUSION: Patients frequently exhibit symptoms of lightheadedness, fatigue, palpitations and syncope. Patients with POTS may have Ehlers-Danlos syndrome, mitral valve prolapse, chronic fatigue syndrome or, rarely, the Brugada syndrome. Despite widespread dissemination of information regarding POTS in the medical literature, scant information on it has appeared in dental publications.

PRACTICE IMPLICATIONS: Dentists need to be familiar with the clinical features of POTS and be prepared to treat patients at risk of developing syncope.

PMID: 16637478

Hypertension. 2006 Mar;47(3):522-6. Epub 2006 Jan 3.

Clonidine for the treatment of supine hypertension and pressure natriuresis in autonomic failure.

Shibao C, Gamboa A, Abraham R, Raj SR, Diedrich A, Black B, Robertson D, Biaggioni I.

Division of Clinical Pharmacology, Department of Medicine and Pharmacology, The Autonomic Dysfunction Center, Vanderbilt University School of Medicine, Nashville, TN, USA.

Patients with autonom ic failure are disabled by orthostatic hypotension, which can be worsened by the nighttime pressure natriuresis induced by associated supine hypertension. Several pharmacological agents are available that effectively reduce nighttime hypertension, but none of them prevent pressure natriuresis. Because hypertension of autonomic failure can be driven by residual sympathetic tone, we hypothesized that clonidine would be effective in reducing blood pressure (BP) and nocturnal natriuresis. Therefore, we determined the effect of placebo, 0.1 mg clonidine, and 0.1-mg/h nitroglycerin transdermal patch on supine BP, orthostatic hypotension, and pressure natriuresis in 23 patients with primary autonomic failure and supine hypertension. Medications were given at 8:00 PM, and BP was recorded every 2 hours for 12 hours. The maximal decrease in BP was seen 6 to 8 hours after drug administration and was similar to clonidine and nitroglycerin (-29+/-9 and -30+/-10 mm Hg, respectively), as was the average fall in BP throughout the night. However, only clonidine effectively reduced nocturnal natriuresis (-0.09 mmol/mg Cr; 95% CI, -0.13 to -0.04; P=0.004), but this was not associated with improvement in morning orthostatic hypotension because of a residual hypotensive effect. The decrease in BP induced by clonidine was modestly but significantly correlated with the magnitude of residual sympathetic tone determined in 10 subjects by the fall in BP induced by ganglionic blockade (r=0.66; P=0.043). These results are consistent with residual sympathetic tone contributing to supine hypertension in autonomic failure, which can be targeted with clonidine to decrease BP and nocturnal natriuresis.

PMID: 16391172

Hypertension. 2006 Jun 19

Sodium Paradoxically Reduces the Gastropressor Response in Patients With Orthostatic Hypotension.

Raj SR, Biaggioni I, Black BK, Rali A, Jordan J, Taneja I, Harris PA, Robertson D.

Autonomic Dysfunction Center, Division of Clinical Pharmacology, Departments of Medicine, Pharmacology, Neurology, and Biomedical Informatics, Vanderbilt University, Nashville, Tenn; and Franz-Volhard Clinical Research Center, Medical Faculty of the Charite and Helios Klinikum, Berlin, Germany.

Orthostatic hypotension (OH) can cause syncope that is difficult to treat. We have found that 473 mL (16 oz) of water can increase systolic blood pressure (SBP) by >30 mm Hg in many OH patients (the gastropressor response). OH patients are routinely advised to increase their sodium intake to augment their blood volume. We tested the hypothesis that the ingestion of salt with water would increase the magnitude of the acute pressor response compared with water alone in patients with OH. Patients with OH (n=9; female=5; 65+/-3 years) underwent a randomized crossover trial of drinking water (H2O) and salt water (NaCl-H2O). Noninvasive heart rate and BP were measured with the patient seated for >/=60 minutes after ingestion. The area under the curve for SBP was greater with H2O than NaCl-H2O for the 30 minutes (714+/-388 mm Hgxmin versus 364+/-369 mm Hgxmin; P=0.002) and 60 minutes (1454+/-827 mm Hgxmin versus 812+/-734 mm Hgxmin; P=0.048) after ingestion. The increase in SBP with H2O was greater than with NaCl-H2O at 30 minutes (37+/-6 versus 18+/-5 mm Hg; P=0.006) but not at 60 minutes (17+/-6 versus 10+/-6 mm Hg; P=0.4). Norepinephrine increased after H2O (P=0.018) but not after NaCl-H2O (P=0.195). Both oral water and salt water increase BP in patients with OH. Instead of augmenting the gastropressor response, the additional salt paradoxically attenuates the pressor response to water. These data suggest a potentially important role for gastrointestinal osmolality in the activation of the sympathetic nervous system leading to cardiovascular reflexes responsible for the gastropressor response.

PMID: 16785332

Clin Sci (Lond). 2006 Feb;110(2):255-63.

Increased plasma angiotensin II in postural tachycardia syndrome (POTS) is related to reduced blood flow and blood volume.

Stewart JM, Glover JL, Medow MS.

Center for Pediatric Hypotension, New York Medical College, Valhalla, NY 10595, USA. stewart@nymc.edu

POTS (postural tachycardia syndrome) is associated with low blood volume and reduced renin and aldosterone; however, the role of Ang (angiotensin) II has not been investigated. Previous studies have suggested that a subset of POTS patients with increased vasoconstriction related to decreased bioavailable NO (nitric oxide) have decreased blood volume. Ang II reduces bioavailable NO and is integral to the renin-Ang system. Thus, in the present study, we investigated the relationship between blood volume, Ang II, renin, aldosterone and peripheral blood flow in POTS patients. POTS was diagnosed by 70 degrees upright tilt, and supine calf blood flow, measured by venous occlusion plethysmography, was used to subgroup POTS patients. A total of 23 POTS patients were partitioned; ten with low blood flow, eight with normal flow and five with high flow. There were ten healthy volunteers. Blood volume was measured by dye dilution. All biochemical measurements were performed whilst supine. Blood volume was decreased in low-flow POTS (2.14 +/- 0.12 litres/m2) compared with controls (2.76 +/- 0.20 litres/m2), but not in the other subgroups. PRA (plasma renin activity) was decreased in low-flow POTS compared with controls (0.49 +/- 0.12 compared with 0.90 +/- 0.18 ng of Ang I.ml(-1).h(-1) respectively), whereas plasma Ang II was increased (89 +/- 20 compared with 32 +/- 4 ng/l), but not in the other subgroups. PRA correlated with aldosterone (r = +0.71) in all subjects. PRA correlated negatively with blood volume (r = -0.72) in normal- and high-flow POTS, but positively (r = +0.65) in low-flow POTS. PRA correlated positively with Ang II (r = +0.76) in normal- and high-flow POTS, but negatively (r = -0.83) in low-flow POTS. Blood volume was negatively correlated with Ang II (r = -0.66) in normal- and high-flow POTS and in five low-flow POTS patients. The remaining five low-flow POTS patients had reduced blood volume and increased Ang II which was not correlated with blood volume. The data suggest that plasma Ang II is increased in low-flow POTS patients with hypovolaemia, which may contribute to local blood flow dysregulation and reduced NO bioavailability.

PMID: 16262605

Am J Physiol Heart Circ Physiol. 2006 Mar 24;

Postural Hypocapnic Hyperventilation is Associated with Enhanced Peripheral Vasoconstriction in Postural Tachycardia Syndrome with Normal Supine Blood Flow.

Stewart JM, Medow MS, Cherniack NS, Natelson BH.

Pediatrics, New York Medical College, Valhalla, New York, United States; Physiology, New York Medical College, Valhalla, New York, United States.

Previous investigations have demonstrated a subset of POTS patients characterized by normal peripheral resistance and blood volume while supine, but thoracic hypovolemia and splanchnic blood pooling while upright secondary to splanchnic hyperemia. Such "normal flow" POTS patients often demonstrate hypocapnia during orthostatic stress. We studied 20 POTS patients aged 14-23 years and compared them to 10 comparably aged healthy volunteers. We measured changes in heart rate, blood pressure, heart rate and blood pressure variability, arm and leg strain gauge occlusion plethysmography (SPG), respiratory impedance plethysmography calibrated against pneumotachography, end tidal carbon dioxide (PETCO2), and impedance plethysmographic (IPG) indices of blood volume and blood flow within the thoracic, splanchnic, pelvic (upper leg), and lower leg regional circulations while supine and during upright tilt to 70 degrees . Ten POTS patients demonstrated significant hyperventilation and hypocapnia (POTSHC) while 10 were normocapneic (POTSNCwith minimal increase in postural ventilation comparable to control. While relative splanchnic hypervolemia and hyperemia occurred in both POTS groups compared to controls, marked enhancement in peripheral vasoconstriction occurred only in POTSHC and was related to thoracic blood flow. Variability indices suggested enhanced sympathetic activation in POTSHC compared to other subjects. The data suggest enhanced cardiac and peripheral sympathetic excitation in POTSHC.

PMID: 16565300

Research abstracts obtained from PubMed.

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