Objective Power spectral analysis of heart rate variability is used clinically to assess cardiac autonomic function. High frequency power is related to respiratory sinus arrhythmia and therefore to parasympathetic cardiovagal tone. The relationship of low frequency (LF) power to cardiac sympathetic tone is less clear. We reported previously that LF power may reflect baroreflex function; however, in the previous study LF power was not adjusted for possible influences of respiration. In this study we assessed relationships of LF power, including respiration-adjusted LF power (LFa) using the ANSAR ANX 3.0 device, with cardiac sympathetic innervation and baroreflex function in chronic autonomic failure patients who either had or did not have neuroimaging evidence of cardiac sympathetic denervation. Methods Values for LF power with patients seated at baseline and during the Valsalva maneuver were compared between groups with low or normal myocardial concentrations of 6-[18F]fluorodopamine-derived radioactivity. Baroreflex-cardiovagal gain (BRS) was calculated from the slope of cardiac interbeat interval vs. systolic pressure during the Valsalva maneuver with subjects supine. Results Individual values for LF and LFa were unrelated to myocardial 6-[18F]fluorodopamine-derived radioactivity. During both sitting rest and the Valsalva maneuver the logs of LF and LFa correlated positively with the log of BRS (r=0.61, p=0.0005; r=0.47, p=0.009; r=0.69, p<0.0001; r=0.60, p=0.0006). Patients with low BRS (≤3 msec/mm Hg) had low LF and LFa regardless of the status of cardiac innervation. Conclusion LF and LFa reflect baroreflex function independently of cardiac sympathetic innervation.

LF power reflects baroreflex function, not cardiac sympathetic innervation.

Abstract-Supine hypertension occurs commonly in primary chronic autonomic failure. This study explored whether supine hypertension in this setting is associated with orthostatic hypotension (OH), and if so, what mechanisms might underlie this association. Supine and upright blood pressures, hemodynamic responses to the Valsalva maneuver, baroreflex-cardiovagal gain, and plasma norepinephrine (NE) levels were measured in pure autonomic failure (PAF), multiple-system atrophy (MSA) with or without OH, and Parkinson's disease (PD) with or without OH. Controls included age-matched, healthy volunteers and patients with essential hypertension or those referred for dysautonomia. Baroreflex-cardiovagal gain was calculated from the relation between the interbeat interval and systolic pressure during the Valsalva maneuver. PAF, MSA with OH, and PD with OH all featured supine hypertension, which was equivalent in severity to that in essential hypertension, regardless of fludrocortisone treatment. Among patients with PD or MSA, those with OH had higher mean arterial pressure during supine rest (109Ϯ3 mm Hg) than did those lacking OH (96Ϯ3 mm Hg, Pϭ0.002). Baroreflex-cardiovagal gain and orthostatic increments in plasma NE levels were markedly decreased in all 3 groups with OH. Among patients with PD or MSA, those with OH had much lower mean baroreflex-cardiovagal gain (0.74Ϯ0.10 ms/mm Hg) than did those lacking OH (3.13Ϯ0.72 ms/mm Hg, Pϭ0.0002). In PAF, supine hypertension is linked to both OH and low baroreflex-cardiovagal gain. The finding of lower plasma NE levels in patients with than without supine hypertension suggests involvement of pressor mechanisms independent of the sympathetic nervous system. Key Words: hypertension, essential Ⅲ hypotension Ⅲ Parkinson's disease Ⅲ autonomic nervous system Ⅲ sympathetic nervous system Ⅲ norepinephrine P rimary chronic autonomic failure has been classified clinically into 3 forms: pure autonomic failure (PAF), multiple-system atrophy (MSA), and autonomic failure in the setting of Parkinson's disease (PD). 1 All 3 forms typically include orthostatic hypotension (OH), wherein reflexive increases in sympathetic neurocirculatory tone fail to compensate adequately for decreased venous return to the heart.Patients with primary chronic autonomic failure also often have supine hypertension. 2 Because of widespread use of the salt-retaining steroid fludrocortisone to treat OH and literature documenting increases in blood pressure secondary to mineralocorticoid administration, 3,4 supine hypertension in primary chronic autonomic failure might be a side effect of treating the OH and not part of the disease; however, supine hypertension has been reported in a substantial proportion of untreated patients. 5 Analogously, levodopa is a mainstay in the treatment of PD, and based on literature that levodopa produces OH, 6 OH in PD might be a side effect of treating the movement disorder and not part of the disease; however, OH occurs in at least some patients with PD who are off or have never been ...

Abstract-Patients with Parkinson disease often have orthostatic hypotension. Neurocirculatory abnormalities underlying orthostatic hypotension might reflect levodopa treatment. Sixty-six Parkinson disease patients (36 with orthostatic hypotension, 15 off and 21 on levodopa; 30 without orthostatic hypotension) had tests of reflexive cardiovagal gain (decrease in interbeat interval per unit decrease in systolic pressure during the Valsalva maneuver; orthostatic increase in heart rate per unit decrease in pressure); reflexive sympathoneural function (decrease in pressure during the Valsalva maneuver; orthostatic increment in plasma norepinephrine); and cardiac and extracardiac noradrenergic innervation (septal myocardial 6-͓ 18 F͔fluorodopamine-derived radioactivity; supine plasma norepinephrine). Severity of orthostatic hypotension did not differ between the levodopa-untreated and levodopa-treated groups with Parkinson disease and orthostatic hypotension (Ϫ52Ϯ6 ͓SEM͔ versus Ϫ49Ϯ5 mm Hg systolic). The 2 groups had similarly low reflexive cardiovagal gain (0.84Ϯ0.23 versus 1.33Ϯ0.35 ms/mm Hg during Valsalva; 0.43Ϯ0.09 versus 0.27Ϯ0.06 bpm/mm Hg during orthostasis); and had similarly attenuated reflexive sympathoneural responses (97Ϯ29 versus 71Ϯ23 pg/mL during orthostasis; Ϫ82Ϯ10 versus Ϫ73Ϯ8 mm Hg during Valsalva). In patients off levodopa, plasma norepinephrine was lower in those with (193Ϯ19 pg/mL) than without (348Ϯ46 pg/mL) orthostatic hypotension. Low values for reflexive cardiovagal gain, sympathoneural responses, and noradrenergic innervation were strongly related to orthostatic hypotension. Parkinson disease with orthostatic hypotension features reflexive cardiovagal and sympathoneural failure and cardiac and partial extracardiac sympathetic denervation, independent of levodopa treatment. Key Words: hypotension Ⅲ sympathetic nervous system Ⅲ norepinephrine Ⅲ baroreflex P rimary chronic autonomic failure syndromes have been classified clinically in 3 forms: pure autonomic failure (PAF), multiple system atrophy (MSA), and Parkinson disease (PD) with autonomic failure. 1 All 3 forms feature neurogenic orthostatic hypotension (OH), supine hypertension, 2,3 and attenuation of the orthostatic increase in the plasma level of norepinephrine (NE), the sympathetic neurotransmitter. 4,5 Levodopa is a precursor of dopamine and therefore of NE. In the treatment of PD, levodopa is usually combined with an inhibitor of L-aromatic-acid-decarboxylase, such as carbidopa, which does not penetrate the blood-brain barrier. Combined levodopa/carbidopa treatment therefore augments delivery of levodopa to the brain and mitigates nausea and vomiting thought to result from occupation of dopamine receptors outside the blood-brain barrier. Combined levodopa/carbidopa treatment attenuates but does not prevent catecholamine synthesis from levodopa outside the brain. 6,7 Reflexive cardiovagal gain has been reported to be variably decreased in PD 8,9 and markedly decreased in PDϩOH. 10 Levodopa treatment of PD can affect reflexive cardiov...

Background Patients with Parkinson disease (PD) often have manifestations of autonomic failure. About 40% have neurogenic orthostatic hypotension (NOH), and among PD+NOH patients virtually all have evidence of cardiac sympathetic denervation; however, whether PD+NOH entails extra-cardiac noradrenergic denervation has been less clear. Methods Microdialysate concentrations of the main neuronal metabolite of norepinephrine (NE), dihydroxyphenylglycol (DHPG), were measured in skeletal muscle, and plasma concentrations of norepinephrine and DHPG were measured in response to i.v. tyramine, yohimbine, and isoproterenol, in patients with PD+NOH, patients with pure autonomic failure (PAF), which is characterized by generalized catecholaminergic denervation, and control subjects. Results Microdialysate DHPG concentrations were similarly low in PD+NOH and PAF, compared to control subjects (163±25, 153±27, and 304±27 pg/ml, p<0.01 each vs. control). The two groups also had similarly small plasma DHPG responses to tyramine (71±58 and 82±105 vs. 313±94 pg/ml; p<0.01 each vs. control) and NE responses to yohimbine (223±37 and 61±15 vs. 672±130 pg/ml, p<0.01 each vs. control) and virtually absent NE responses to isoproterenol (20±34 and 14±15 vs. 336±78 pg/ml, p<0.01 each vs. control). PD+NOH patients had normal bradycardia responses to edrophonium and normal epinephrine responses to glucagon Conclusions The results support the concept of generalized noradrenergic denervation in PD+NOH, with similar severity to that seen in PAF. In contrast, the parasympathetic cholinergic and adrenomedullary hormonal components of the autonomic nervous system seem intact in PD+NOH.

Background-Chronic orthostatic intolerance (COI) occurs in postural tachycardia syndrome (POTS)

Background-Power spectral analysis of heart rate variability (HRV) has been used to indicate cardiac autonomic function. High-frequency power relates to respiratory sinus arrhythmia and therefore to parasympathetic cardiovagal tone; however, the relationship of low-frequency (LF) power to cardiac sympathetic innervation and function has been controversial. Alternatively, LF power might reflect baroreflexive modulation of autonomic outflows.

The PD + OH resembles PAF and differs from MSA in hemodynamic responses to drugs that alter NE release from sympathetic nerves. The results fit with sympathetic noradrenergic denervation in PD + OH and PAF but not in MSA.