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Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) with orthostatic intolerance (OI) is characterized by neurocognitive deficits perhaps related to upright hypocapnia and loss of cerebral autoregulation (CA). We performed N-back neurocognition testing and calculated the phase synchronization index (PhSI) between arterial pressure (AP) and cerebral blood velocity (CBV) as a time-dependent measurement of cerebral autoregulation in 11 control (mean age = 24.1 yr) and 15 patients with ME/CFS (mean age = 21.8 yr). All patients with ME/CFS had postural tachycardia syndrome (POTS). A 10-min 60° head-up tilt (HUT) significantly increased heart rate (109.4 ± 3.9 vs. 77.2 ± 1.6 beats/min, P < 0.05) and respiratory rate (20.9 ± 1.7 vs. 14.2 ± 1.2 breaths/min, P < 0.05) and decreased end-tidal CO2 (ETCO2; 33.9 ± 1.1 vs. 42.8 ± 1.2 Torr, P < 0.05) in ME/CFS versus control. In ME/CFS, HUT significantly decreased CBV compared with control (-22.5% vs. -8.7%, P < 0.005). To mitigate the orthostatic CBV reduction, we administered supplemental CO2, phenylephrine, and acetazolamide and performed N-back testing supine and during HUT. Only phenylephrine corrected the orthostatic decrease in neurocognition by reverting % correct n = 4 N-back during HUT in ME/CFS similar to control (ME/CFS = 38.5 ± 5.5 vs. ME/CFS þ PE= 65.6 ± 5.7 vs. Control 56.9 ± 7.5). HUT in ME/CFS resulted in increased PhSI values indicating decreased CA. Although CO2 and acetazolamide had no effect on PhSI in ME/CFS, phenylephrine caused a significant reduction in PhSI (ME/CFS = 0.80 ± 0.03 vs. ME/CFS þ PE= 0.69 ± 0.04, P < 0.05) and improved cerebral autoregulation. Thus, PE improved neurocognitive function in patients with ME/CFS, perhaps related to improved neurovascular coupling, cerebral autoregulation, and maintenance of CBV. NEW & NOTEWORTHY We evaluated cognitive function before and after CO2, acetazolamide, and phenylephrine, which mitigate orthostatic reductions in cerebral blood velocity. Neither CO2 nor acetazolamide affected N-back testing (% correct answers) during an orthostatic challenge. Only phenylephrine improved upright N-back performance in ME/CFS, as it both blocked hyperventilation and increased CO2 significantly compared with those untreated. And only phenylephrine resulted in improved PSI values in both ME/CFS and control while upright, suggesting improved cerebral autoregulation. [ABSTRACT FROM AUTHOR]

Fifty percent of patients with postural tachycardia syndrome (POTS) are hypocapnic during orthostasis related to initial orthostatic hypotension (iOH). We determined whether iOH drives hypocapnia in POTS by low BP or decreased cerebral blood velocity (CBv). We studied three groups; healthy volunteers (n = 32, 18 ± 3 yr) were compared with POTS, grouped by presence [POTSlow end-tidal CO2 (;ETCO2), n = 26, 19 ± 2 yr] or absence [POTS-normal upright end-tidal carbon dioxide (nlCO2), n = 28, 19 ± 3 yr] of standing hypocapnia defined by end-tidal CO2 (ETCO2) 30 mmHg at steady-state, measuring middle cerebral artery CBv, heart rate (HR), and beat-to-beat blood pressure (BP). After 30 min supine, subjects stood for 5 min. Quantities were measured prestanding, at minimum CBv, minimum BP, peak HR, CBv recovery, BP recovery, minimum HR, steady-state, and 5 min. Baroreflex gain was estimated by a index. iOH occurred with similar frequency and minimum BP in POTS-;ETCO2 and POTSnlCO2. Minimum CBv was reduced significantly (P < 0.05) in POTS-;ETCO2 (48 ± 3 cm/s) preceding hypocapnia compared with POTS-nlCO2 (61 ± 3 cm/s) or Control (60 ± 2 cm/s). The anticipatory increased BP was significantly larger (P < 0.05) in POTS (8 ± 1 mmHg vs. 2 ± 1) and began 8 s prestanding. HR increased in all subjects, CBv increased significantly (P < 0.05) in both POTSnlCO2 (76 ± 2 to 85 ± 2 cm/s) and Control (75 ± 2 to 80 ± 2 cm/s) consistent with central command. CBv decreased in POTS-; ETCO2 (76 ± 3 to 64 ± 3 cm/s) correlating with decreased baroreflex gain. Cerebral conductance [meanCBv/mean arterial blood pressure (MAP)] was reduced in POTS-;ETCO2 throughout. Data support the hypothesis that excessively reduced CBv during iOH may intermittently reduce carotid body blood flow, sensitizing that organ and producing postural hyperventilation in POTS-; ETCO2. Excessive fall in CBv occurs in part during prestanding central command and is a facet of defective parasympathetic regulation in POTS. [ABSTRACT FROM AUTHOR]

Ocon A J, Kulesa J, Clarke D, Taneja I, Medow MS, Stewart JM. Increased phase synchronization and decreased cerebral autoregulation during fainting in the young. Am J Physiol Heart Circ Physiol 297: H2084-H2095, 2009. First published October 9, 2009; doi: 10.1152/ajpheart.00705.2009.--Vasovagal syncope may be due to a transient cerebral hypoperfusion that accompanies frequency entrainment between arterial pressure (AP) and cerebral blood flow velocity (CBFV). We hypothesized that cerebral autoregulation fails during fainting; a phase synchronization index (PhSI) between AP and CBFV was used as a nonlinear, nonstationary, time-dependent measurement of cerebral autoregulation. Twelve healthy control subjects and twelve subjects with a history of vasovagal syncope underwent 10-min tilt table testing with the continuous measurement of AP, CBFV, heart rate (HR), end-tidal C[O.sub.2] (ET[co.sub.2]), and respiratory frequency. Time intervals were defined to compare physiologically equivalent periods in fainters and control subjects. A PhSI value of 0 corresponds to an absence of phase synchronization and efficient cerebral autoregulation, whereas a PhSI value of 1 corresponds to complete phase synchronization and inefficient cerebral autoregulation. During supine baseline conditions, both control and syncope groups demonstrated similar oscillatory changes in phase, with mean PhSI values of 0.58 [+ or -] 0.04 and 0.54 [+ or -] 0.02, respectively. Throughout tilt, control subjects demonstrated similar PhSI values compared with supine conditions. Approximately 2 min before fainting, syncopal subjects demonstrated a sharp decrease in PhSI (0.23 [+ or -] 0.06), representing efficient cerebral autoregulation. Immediately after this period, PhSI increased sharply, suggesting inefficient cerebral autoregulation, and remained elevated at the time of faint (0.92 [+ or -] 0.02) and during the early recovery period (0.79 [+ or -] 0.04) immediately after the return to the supine position. Our data demonstrate rapid, biphasic changes in cerebral autoregulation, which are temporally related to vasovagal syncope. Thus, a sudden period of highly efficient cerebral autoregulation precedes the virtual loss of autoregulation, which continued during and after the faint. syncope; cerebral blood flow; nonlinear; cerebral blood flow velocity doi: 10.1152/ajpheart.00705.2009

Postural tachycardia syndrome (POTS), a chronic form of orthostatic intolerance, has signs and symptoms of lightheadedness, loss of vision, headache, fatigue, and neurocognitive deficits consistent with reductions in cerebrovascular perfusion. We hypothesized that young, normocapnic POTS patients exhibit abnormal cerebral autoregulation (CA) that results in decreased static and dynamic cerebral blood flow (CBF) autoregulation. All subjects had continuous recordings of mean arterial pressure (MAP) and CBF velocity (CBFV) using transcranial Doppler sonography in both the supine supine position and during a 70[degrees] head-up tilt. During tilt, POTS patients (n = 9) demonstrated a higher heart rate than controls (n = 7) (109 [+ or -] 6 vs. 80 [+ or -] 2 beats/min, P < 0.05), whereas controls demonstrated a higher MAP than POTS (87 [+ or -] 2 vs. 77 [+ or -] 3 mmHg, P < 0.05). Also during tilt, mean CBFV decreased 19.5 [+ or -] 2.6% in POTS patients versus 10.3 [+ or -] 2.0% in controls (P < 0.05). We then used a transfer function analysis of MAP and CFBV in the frequency domain to quantify these changes. The low-frequency (LF; 0.04-0.15 Hz) component of CBFV variability increased during tilt in POTS patients (supine: 3 [+ or -] 0.9 vs. tilt: 9 [+ or -] 2, P < 0.02). In POTS patients, there was an increase in LF and high-frequency coherence between MAP and CBFV, an increase in LF gain, and a lack of significant change in phase. Static CA may be less effective in POTS patients compared with controls, since immediately after tilt CBFV decreased more in POTS patients and was highly oscillatory and autoregulation did not restore CBFV to baseline values until the subjects became supine. Dynamic CA may be less effective in POTS patients because MAP and CBFV during tilt became almost perfectly synchronous. We conclude that dynamic and static autoregulation of CBF are less effective in POTS patients compared with control subjects during orthostatic challenge. chronic orthostasis; coherence; transcranial Doppler

Our prior studies indicated that postural fainting relates to thoracic hypovolemia. A supranormal increase in initial vascular resistance was sustained by increased peripheral resistance until late during head-up tilt (HUT), whereas splanchnic resistance, cardiac output, and blood pressure (BP) decreased throughout HUT. Our aim in the present study was to investigate the alterations of baroreflex activity that occur in synchrony with the beat-to-beat time-dependent changes in heart rate (HR), BP, and total peripheral resistance (TPR). We proposed that changes of low-frequency Mayer waves reflect sympathetic baroreflex. We used DWT multiresolution analyses to measure their time dependence. We studied 22 patients, 13 to 21 yr old, 14 who fainted within 10 min of upright tilt (fainters) and 8 healthy control subjects. Multiresolution analysis was obtained of continuous BP, HR, and respirations as a function of time during 70[degrees] upright tilt at different scales corresponding to frequency bands. Wavelet power was concentrated in scales corresponding to 0.125 and 0.25 Hz. A major difference from control subjects was observed in fainters at the 0.125 Hz AP scale, which progressively decreased from early HUT. The alpha index at 0.125 Hz was increased in fainters. RR interval 0.25 Hz power decreased in fainters and controls but was markedly increased in fainters with syncope and thereafter corresponding to increased vagal tone compared with control subjects at those times only. The data imply a rapid reduction in time-dependent sympathetic baroreflex activity in fainters but not control subjects during HUT. baroreflex; syncope; variance

Our prior studies indicated that postural fainting relates to splanchnic hypervolemia and thoracic hypovolemia during orthostasis. We hypothesized that thoracic hypovolemia causes excessive sympathetic activation, increased respiratory tidal volume, and fainting involving the pulmonary stretch reflex. We studied 18 patients 13-21 yr old, 11 who fainted within 10 min of upright tilt (fainters) and 7 healthy control subjects. We measured continuous blood pressure and heart rate, respiration by inductance plethysmography, end-tidal carbon dioxide ([MATHEMATICAL EXPRESSION NOT REPRODUCIBLE IN ASCII]) by capnography, and regional blood flows and blood volumes using impedance plethysmography, and we calculated arterial resistance with patients supine and during 70[degrees] upright tilt. Splanchnic resistance decreased until faint in fainters (44 [+ or -] 8 to 21 [+ or -] 2 mmHg*[l.sup.-1]*[min.sup.-1]) but increased in control subjects (47 [+ or -] 5 to 53 [+ or -] 4 mmHg*[l.sup.-1][min.sup.-1]). Percent change in splanchnic blood volume increased (7.5 [+ or -] 1.0 vs. 3.0 [+ or -] 11.5%, P < 0.05) after the onset of tilt. Upright tilt initially significantly increased thoracic, pelvic, and leg resistance in fainters, which subsequently decreased until faint. In fainters but not control subjects, normalized tidal volume (1 [+ or -] 0.1 to 2.6 [+ or -] 0.2, P < 0.05) and normalized minute ventilation increased throughout tilt (1 [+ or -] 0.2 to 2.1 [+ or -] 0.5, P < 0.05), whereas respiratory rate decreased (19 [+ or -] 1 to 15 [+ or -] 1 breaths/min, P < 0.05). Maximum tidal volume occurred just before fainting. The increase in minute ventilation was inversely proportionate to the decrease in [MATHEMATICAL EXPRESSION NOT REPRODUCIBLE IN ASCII]. Our data suggest that excessive splanchnic pooling and thoracic hypovolemia result in increased peripheral resistance and hyperpnea in simple postural faint. Hyperpnea and pulmonary stretch may contribute to the sympathoinhibition that occurs at the time of faint. splanchnic resistance; total peripheral resistance; minute ventilation; regional blood flow

The vasodilation response to local cutaneous heating is nitric oxide (NO) dependent and blunted in postural tachycardia hut reversed by angiotensin II (ANG II) type 1 receptor (ATIR) blockade. We tested the hypothesis that a localized infusion of ANG II attenuates vasodilation to local heating in healthy volunteers. We heated the skin of a calf to 42[degrees]C and measured local blood flow to assess the percentage of maximum cutaneous vascular conductance (%[CVC.sub.max]) in eight healthy volunteers aged 19.5-25.5 years. Initially, two experiments were performed; in one, Ringer solution was perfused in three catheters, the response to heating was measured, 2 [micro]g/1 losartan, 10 mM nitro-L-arginine (NLA), or NLA + losartan was added to perfusate, and the heat response was remeasured; in another, 10 p~M ANG II was given, the heat response was measured, losartan, NLA, or NLA + losartan was added to ANG II, and the heat response was reassessed. The heat response decreased with ANG II, particularly the plateau phase (47 [+ or -] 5 vs. 84 [+ or -] 3 %[CVC.sub.max]). Losartan increased baseline conductance in both experiments (from 8 [+ or -] 1 to 20 [+ or -] 2 and 12 [+ or -] 1 to 24 [+ or -] 3). Losartan increased the ANG II response (83 [+ or -] 4 vs. 91 [+ or -] 6 in Ringer). NLA decreased both angiotensin and Ringer responses (31 [+ or -] 4 vs. 43 [+ or -] 3). NLA + losartan blunted the Ringer response (48 [+ or -] 2), but the ANG II response (74 [+ or -] 5) increased. In a second set of experiments, we used dose responses to ANG II (0.1 nM to 10 [micro]M) with and without NLA + losartan to confirm graded responses. Sodium ascorbate (10 mM) restored the ANG II-blunted heating plateau. NO synthase and ATIR inhibition cause an NO-independent angiotensin-mediated vasodilation with local heating. ANG II mediates the AT~R blunting of local heating, which is not exclusively NO dependent, and is improved by antioxidant supplementation. lasers; conductance; skin

Low-flow postural tachycardia syndrome (POTS) is associated with increased plasma angiotensin II (ANG II) and reduced neuronal nitric oxide (NO), which decreases NO-dependent vasodilation. We tested whether the ANG II type 1 receptor ([AT.sub.1]R) antagonist losartan would improve NO-dependent vasodilation in POTS patients. Furthermore, if the action of ANG II is dependent on NO, then the NO synthase inhibitor nitro-L-arginine (NLA) would reverse this improvement. We used local heating of the skin of the left calf to 42[degrees]C and laser-Doppler flowmetry to assess NO-dependent conductance [percent maximum cutaneous vascular conductance (%[CVC.sub.max])] in 12 low-flow POTS patients aged 22.5 [+ or -] 0.8 yr and in 15 control subjects aged 22.0 [+ or -] 1.3 yr. After measuring the baseline local heating response at three separate sites, we perfused individual intradermal microdialysis catheters at those sites with 2 [micro]g/l losartan, 10 mM NLA, or losartan + NLA. The predrug heat response was reduced in POTS, particularly the plateau phase reflecting NO-dependent vasodilation (50 [+ or 1] 5 vs. 91 [+ or -] 7 %[CVC.sub.max]; P < 0.001 vs. control). Losartan increased baseline flow in both POTS and control subjects (from 6 [+ or -] 1 to 21 [+ or -] 3 vs. from 10 [+ or -] 1 to 21 [+ or -] 2 %[CVC.sub.max]; P < 0.05 compared with predrug). The baseline increase was blunted by NLA. Losartan increased the POTS heat response to equal the control subject response (79 [+ or -] 7 vs. 88 [+ or -] 6 %[CVC.sub.max]; P = 0.48). NLA decreased both POTS and control subject heat responses to similar conductances (38 [+ or -] 4 vs. 38 [+ or -] 3 %[CVC.sub.max]; P < 0.05 compared with predrug). The addition of NLA to losartan reduced POTS and control subject conductances compared with losartan alone (48 [+ or -] 3 vs. 53 [+ or -] 2 %[CVC.sub.max]). The data suggest that the reduction in cutaneous NO-dependent vasodilation in low-flow POTS is corrected by [AT.sub.1]R blockade. lasers; autonomic nervous system

Low flow postural tachycardia syndrome (POTS), is associated with reduced nitric oxide (NO) activity assumed to be of endothelial origin. We tested the hypothesis that cutaneous microvascular neuronal NO (nNO) is impaired, rather than endothelial NO (eNO), in POTS. We performed three sets of experiments on subjects aged 22.5 [+ or -] 2 yr. We used laser-Doppler flowmetry response to sequentially increase acetylcholine (ACh) doses and the local cutaneous heating response of the calf as bioassays for NO. During local heating we showed that when the selective neuronal nNO synthase (nNOS) inhibitor [N.sup.[omega]]-nitro-L-arginine-2,4-L-diaminobutyric amide ([N.sup.[omega]], 10 mM) was delivered by intradermal microdialysis, cutaneous vascular conductance (CVC) decreased by an amount equivalent to the largest reduction produced by the nonselective NO synthase (NOS) inhibitor nitro-L-arginine (NLA, 10 mM). We demonstrated that the response to ACh was minimally attenuated by nNOS blockade using [N.sup.[omega]] but markedly attenuated by NLA, indicating that eNO largely comprises the receptor-mediated NO release by ACh. We further demonstrated that the ACh dose response was minimally reduced, whereas local heatmediated NO-dependent responses were markedly reduced in POTS compared with control subjects. This is consistent with intact endothelial function and reduced NO of neuronal origin in POTS. The local heating response was highly attenuated in POTS [60 [+ or -] 6 percent maximum CVC([%CVC.sub.max])] compared with control (90 [+ or -] 4 [%CVC.sub.max)], but the plateau response decreased to the same level with nNOS inhibition (50 [+ or -] 3 [%CVC.sub.max] in POTS compared with 47 [+ or -] 2 [%CVC.sub.max)], indicating reduced nNO bioavailability in POTS patients. The data suggest that nNO activity but not NO of endothelial NOS origin is reduced in low-flow POTS. lasers; autonomic nervous system

Postural tachycardia syndrome (POTS) is characterized by exercise intolerance and sympathoactivation. To examine whether abnormal cardiac output and central blood volume changes occur during exercise in POTS, we studied 29 patients with POTS (17-29 yr) and 12 healthy subjects (18-27 yr) using impedance and venous occlusion plethysmography to assess regional blood volumes and flows during supine static handgrip to evoke the exercise pressor reflex. POTS was subgrouped into normal and low-flow groups based on calf blood flow. We examined autonomic effects with variability techniques. During hand-grip, systolic blood pressure increased from 112 [+ or -] 4 to 139 [+ or -] 9 mmHg in control, from 119 [+ or -] 6 to 143 [+ or -] 9 in normal-flow POTS, but only from 117 [+ or -] 4 to 128 [+ or -] 6 in low-flow POTS. Heart rate increased from 63 [+ or -] 6 to 82 [+ or -] 4 beats/min in control, 76 [+ or -] 3 to 92 [+ or -] 6 beats/rain in normal-flow POTS, and 88 [+ or -] 4 to 100 [+ or -] 6 beats/min in low-flow POTS. Heart rate variability and coherence markedly decreased in low-flow POTS, indicating uncoupling of baroreflex heart rate regulation. The increase in central blood volume with handgrip was absent in low-flow POTS and blunted in normal-flow POTS associated with abnormal splanchnic emptying. Cardiac output increased in control, was unchanged in low-flow POTS, and was attenuated in normal-flow POTS. Total peripheral resistance was increased compared with control in all POTS. The exercise pressor reflex was attenuated in low-flow POTS. While increased cardiac output and central blood volume characterizes controls, increased peripheral resistance with blunted or eliminated in central blood volume increments characterizes POTS and may contribute to exercise intolerance. orthostatic intolerance; mechanoreflex; metaboreflex; regional blood volume; exercise intolerance

We tested the hypothesis that cyclooxygenases (COXs) or COX products inhibit nitric oxide (NO) synthesis and thereby mask potential effects of NO on reactive hyperemia in the cutaneous circulation. We performed laser-Doppler flowmetry (LDF) with intradermal microdialysis in 12 healthy volunteers aged 19-25 yr. LDF was expressed as the percent cutaneous vascular conduction (%CVC)or as the maximum %CVC (%CVCmax) where CVC is LDF/mean arterial pressure. We tested the effects of the nonisoform-specific NO synthase inhibitor nitro-L-arginine (NLA, 10 mM), the nonspecific COX inhibitor ketorolac (Keto, 10 mM), combined NLA + Keto, and NLA + sodium nitroprusside (SNP, 28 mM) on baseline and reactive hyperemia flow parameters. We also examined the effects of isoproterenol, a [beta]-adrenergic agonist that causes prostaglandin-independent vasodilation to correct for the increase in baseline flow caused by Keto. When delivered directly into the intradermal space, Keto greatly augments all aspects of the laser-Doppler flow response to reactive hyperemia: peak reactive hyperemic flow increased from 41 [+ or -] 5 to 77 [+ or -] 7%[CVC.sub.max], time to peak flow increased from 17 [+ or -] 3 to 56 [+ or -] 24 s, the area under the reactive hyperemic curve increased from 1,417 [+o or -] 326 to 3,376 [+ or -] 876%[CVC.sub.max] x S, and the time constant for the decay of peak flow increased from 100 [+ or -] 23 to 821 [+ or -] 311 s. NLA greatly attenuates the Keto response despite exerting no effects on baseline LDF or on reactive hyperemia when given alone. Low-dose NLA + SNP duplicates the Keto response. Isoproterenol increased baseline and peak reactive flow. These results suggest that COX inhibition unmasks NO dependence of reactive hyperemia in human cutaneous circulation. microdialysis; prostaglandin; skin doi:10.1152/ajpheart.01217.2006

Upright posture and lower body negative pressure (LBNP) both induce reductions in central blood volume. However, regional circulatory responses to postural changes and LBNP may differ. Therefore, we studied regional blood flow and blood volume changes in 10 healthy subjects undergoing graded lower-body negative pressure (-10 to -50 mmHg) and 8 subjects undergoing incremental head-up tilt (HUT; 20[degrees], 40[degrees], and 70[degrees]) on separate days. We continuously measured blood pressure (BP), heart rate, and regional blood volumes and blood flows in the thoracic, splanchnic, pelvic, and leg segments by impedance plethysmography and calculated regional arterial resistances. Neither LBNP nor HUT altered systolic BP, whereas pulse pressure decreased significantly. Blood flow decreased in all segments, whereas peripheral resistances uniformly and significantly increased with both HUT and LBNP. Thoracic volume decreased while pelvic and leg volumes increased with HUT and LBNP. However, splanchnic volume changes were directionally opposite with stepwise decreases in splanchnic volume with LBNP and stepwise increases in splanchnic volume during HUT. Splanchnic emptying in LBNP models regional vascular changes during hemorrhage. Splanchnic filling may limit the ability of the splanchnic bed to respond to thoracic hypovolemia during upright posture. vasoconstriction; splanchnic; blood volume; orthostatic stress; hemorrhage

Increased blood pressure (BP) and heart rate during exercise characterizes the exercise pressor reflex. When evoked by static handgrip, mechanoreceptors and metaboreceptors produce regional changes in blood volume and blood flow, which are incompletely characterized in humans. We studied 16 healthy subjects aged 20-27 yr using segmental impedance plethysmography validated against dye dilution and venous occlusion plethysmography to noninvasively measure changes in regional blood volumes and blood flows. Static handgrip while in supine position was performed for 2 min without postexercise ischemia. Measurements of heart rate and BP variability and coherence analyses were used to examine baroreflex-mediated autonomic effects. During handgrip exercise, systolic BP increased from 120 [+ or -] 10 to 148 [+ or -] 14 mmHg, whereas heart rate increased from 60 [+ or -] 8 to 82 [+ or -] 12 beats/rain. Heart rate variability decreased, whereas BP variability increased, and transfer function amplitude was reduced from 18 [+ or -] 2 to 8 [+ or -] 2 ms/mmHg at low frequencies of ~0.1 Hz. This was associated with marked reduction of coherence between BP and heart rate (from 0.76 [+ or -] 0.10 to 0.26 [+ or -] 0.05) indicative of uncoupling of heart rate regulation by the baroreflex. Cardiac output increased by ~18% with a 4.5% increase in central blood volume and an 8.5% increase in total peripheral resistance, suggesting increased cardiac preload and contractility. Splanchnic blood volume decreased reciprocally with smaller decreases in pelvic and leg volumes, increased splanchnic, pelvic and calf peripheral resistance, and evidence for splanchnic venoconstriction. We conclude that the exercise pressor reflex is associated with reduced baroreflex cardiovagal regulation and driven by increased cardiac output related to enhanced preload, cardiac contractility, and splanchnic blood mobilization. exercise pressor reflex; mechanoreflex; metaboreflex

Previous investigations have demonstrated a subset of postural tachycardia syndrome (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 (14-23 yr of age) and compared them with 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, respiratory impedance plethysmography calibrated against pneumotachography, end-tidal partial pressure of carbon dioxide ([MATHEMATICAL EXPRESSION NOT REPRODUCIBLE IN ASCII.]), and impedance plethysmographic indexes 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 (POT[S.sub.HC]) while 10 were normocapnic with minimal increase in postural ventilation, comparable to control. While relative splanchnic hypervolemia and hyperemia occurred in both POTS groups compared with controls, marked enhancement in peripheral vasoconstriction occurred only in POT[S.sub.HC] and was related to thoracic blood flow. Variability indexes suggested enhanced sympathetic activation in POT[S.sub.HC] compared with other subjects. The data suggest enhanced cardiac and peripheral sympathetic excitation in POT[S.sub.HC]. vasoconstriction; hypocapnia; orthostatic intolerance doi:10.1152/ajpheart.01359.2005

Previous investigations have allowed for stratification of patients with postural tachycardia syndrome (POTS) on the basis of peripheral blood flow. One such subset, comprising 'normal-flow POTS' patients, is characterized by normal peripheral resistance and blood volume in the supine position but thoracic hypovolemia and splanchnic blood pooling in the upright position. We studied 32 consecutive 14- to 22-yr-old POTS patients comprising 13 with low-flow POTS, 14 with normal-flow POTS, and 5 with high-flow POTS and 12 comparably aged healthy volunteers. We measured changes in impedance plethysmographic (IPG) indexes of blood volume and blood flow within thoracic, splanchnic, pelvic (upper leg), and lower leg regional circulations in the supine posture and during incremental tilt to 20[degrees], 35[degrees], and 70[degrees]. We validated IPG measures of thoracic and splanchnic blood flow against indocyanine green dye-dilution measurements. We validated IPG leg blood flow against venous occlusion plethysmography. Control subjects developed progressive vasoconstriction with incremental tilt. Splanchnic blood flow was increased in the supine position in normal-flow POTS, despite marked peripheral vasoconstriction, and did not change during incremental tilt, producing progressive splanchnic hypervolemia. Absolute hypovolemia was present in low-flow POTS, all supine flows and volumes were reduced, there was no vasoconstriction with tilt in all segments, and segmental volumes tended to increase uniformly throughout tilt. Lower body (pelvic and leg) flows were increased in high-flow POTS at all angles, with consequent lower body hypervolemia during tilt. Our main finding is selective and maintained orthostatic splanchnic vasodilation in normal-flow POTS, despite marked peripheral vasoconstriction in these same patients. Local splanchnic vasoregulatory factors may counteract vasoconstriction and venoconstriction in these patients. Lower body vasoconstriction in high-flow POTS was abnormal, and vasoconstriction in low-flow POTS was sustained at initially elevated supine levels. vasoconstriction; blood volume; autonomic; orthostatic intolerance

Prior work demonstrated dependence of the change in blood pressure during the Valsalva maneuver (VM) on the extent of thoracic hypovolemia and splanchnic hypervolemia. Thoracic hypovolemia and splanchnic hypervolemia characterize certain patients with postural tachycardia syndrome (POTS) during orthostatic stress. These patients also experience abnormal phase II hypotension and phase IV hypertension during VM. We hypothesize that reduced splanchnic arterial resistance explains aberrant VM results in these patients. We studied 17 POTS patients aged 15-23 yr with normal resting peripheral blood flow by strain gauge plethysmography and 10 comparably aged healthy volunteers. All had normal blood volumes by dye dilution. We assessed changes in estimated thoracic, splanchnic, pelvic-thigh, and lower leg blood volume and blood flow by impedance plethysmography throughout VM performed in the supine position. Baseline splanchnic blood flow was increased and calculated arterial resistance was decreased in POTS compared with control subjects. Splanchnic resistance decreased and flow increased in POTS subjects, whereas splanchnic resistance increased and flow decreased in control subjects during stage II of VM. This was associated with increased splanchnic blood volume, decreased thoracic blood volume, increased heart rate, and decreased blood pressure in POTS. Pelvic and leg resistances were increased above control and remained so during stage IV of VM, accounting for the increased blood pressure overshoot in POTS. Thus splanchnic hyperemia and hypervolemia are related to excessive phase II blood pressure reduction in POTS despite intense peripheral vasoconstriction. Factors other than autonomic dysfunction may play a role in POTS. vasoconstriction; splanchnic arterial resistance; mesenteric artery; autonomic dysfunction; orthostatic intolerance

Standing translocates thoracic blood volume into the dependent body. The skeletal muscle pump participates in preventing orthostatic intolerance by enhancing venous return. We investigated the hypothesis that skeletal muscle pump function is impaired in postural tachycardia (POTS) associated with low calf blood flow (low-flow POTS) and depends in general on muscle blood flow. We compared 12 subjects that have low-flow POTS with 10 controls and 7 patients that have POTS and normal calf blood flow using strain-gauge plethysmography to measure peripheral blood flow, venous capacitance, and calf muscle pump function. Blood volume was estimated by dye dilution. We found that calf circumference was reduced in low-flow POTS (32 [+ or -] 1 vs. 39 [+ or -] 3 and 43 [+ or -] 3 cm) and, compared with controls and POTS patients with normal blood flow, is related to the reduced fraction of calf venous capacity emptied during voluntary muscle contraction (ejection fraction, 0.52 [+ or -] 0.07 vs. 0.76 [+ or -] 0.07 and 0.80 [+ or -] 0.06). We found that blood flow was linearly correlated ([r.sub.p] = 0.69) with calf circumference (used as a surrogate for muscle mass). Blood volume measurements were 2.2 [+ or -] 0.3 in low-flow POTS vs. 2.6 [+ or -] 0.5 in controls (P = 0.17) and 2.4 [+ or -] 0.7 in normal-flow POTS patients. Decreased calf blood flow may reduce calf size in POTS and thereby impair the upright ejective ability of the skeletal muscle pump and further contribute to overall reduced blood flow and orthostatic intolerance in these patients. orthostatic; capacitance; venous return

Postural tachycardia syndrome (POTS) is defined by orthostatic intolerance associated with abnormal upright tachycardia. Some patients have defective peripheral vasoconstriction and increased calf blood flow. Others have increased peripheral arterial resistance and decreased blood flow. In 14 POTS patients (13-19 yr) evenly subdivided among low-flow POTS (LFP) and high-flow POTS (HFP) we tested the hypothesis that myogenic, venoarteriolar, and reactive hyperemic responses are abnormal. We used venous occlusion plethysmography to measure calf venous pressure and blood flow in the supine position and when the calf was lowered by 40 cm to evoke myogenic and venoarteriolar responses and during venous hypertension by 40-mmHg occlusion to evoke the venoarteriolar response. We measured calf reactive hyperemia with plethysmography and cutaneous laser-Doppler flowmetry. Baseline blood flow in LFP was reduced compared with HFP and control subjects (0.8 [+ or -] 0.2 vs. 4.4 [+ or -] 0.5 and 2.7 [+ or -] 0.4 ml * [min.sup.-1] * 100 [ml.sup.-1]) but increased during leg lowering (1.2 [+ or -] 0.5 ml * [min.sup.-1] * 100 [ml.sup.-1]) while decreasing in the others. Baseline peripheral arterial resistance was increased in LFP and decreased in HFP compared with control subjects (39 [+ or -] 13 vs. 15 [+ or -] 3 and 22 [+ or -] 5 mmHg * [ml.sup.-1] * 100 ml*min) but decreased to 29 [+ or -] 13 mmHg * [ml.sup.-1] * 100 ml * min in LFP during venous hypertension. Resistance increased in the other groups. Maximum calf hyperemic flow and cutaneous flow were similar in all subjects. The duration of hyperemic blood flow was curtailed in LFP compared with either control or HFP subjects (plethysmographic time constant = 20 [+ or -] 2 vs. 29 [+ or -] 4 and 28 [+ or -] 4 s; cutaneous time constant = 60 [+ or -] 25 vs. 149 [+ or -] 53 s in controls). Local blood flow regulation in low-flow POTS is impaired. myogenic vasoconstriction; venoarteriolar vasoconstriction; autonomic vasoconstriction

Children with lactose intolerance have decreased or no activity of lactase (also called beta-galactosidase), an enzyme that is required for the breakdown and absorption of lactose from the intestinal tract. Lactose intolerance is associated with flatulence, abdominal pain, and diarrhea occurring shortly after milk products are consumed (lactose is the main carbohydrate in milk). The effectiveness of lactase-containing tablets in decreasing symptoms associated with lactose intolerance was assessed in 18 children with lactose intolerance but no underlying gastrointestinal disease. The average age was 11 years, and 74 percent of the subjects were boys. Lactase-containing tablets or a placebo, a substance with no therapeutic effect, were taken before drinking a solution of lactose. The breath of the children was analyzed for the levels of hydrogen every 30 minutes for two hours. Hydrogen levels in the breath, which serve as a measure of the inability to break down lactose, were 60 parts per million (ppm) in patients given a placebo and seven ppm in patients give the lactase-containing tablets. Increased hydrogen production was associated with clinical symptoms of lactose intolerance in placebo-treated patients, including abdominal pain in 89 percent, bloating in 83 percent, diarrhea in 61 percent, and flatulence in 44 percent. These findings show that lactase-containing tablets, taken before ingesting lactose, reduce the excretion of hydrogen in the breath and the abdominal symptoms caused by lactose intolerance. (Consumer Summary produced by Reliance Medical Information, Inc.)