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

2006 ◽  
Vol 110 (2) ◽  
pp. 255-263 ◽  
Author(s):  
Julian M. Stewart ◽  
June L. Glover ◽  
Marvin S. Medow
Keyword(s):  
Blood Flow ◽  
Angiotensin Ii ◽  
Blood Volume ◽  
High Flow ◽  
The Other ◽  
Low Flow ◽  
Postural Tachycardia Syndrome ◽  
Peripheral Blood Flow ◽  
Ang Ii ◽  
Postural Tachycardia

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° 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.

scholarly journals Persistent splanchnic hyperemia during upright tilt in postural tachycardia syndrome

2006 ◽  
Vol 290 (2) ◽  
pp. H665-H673 ◽  
Author(s):  
Julian M. Stewart ◽  
Marvin S. Medow ◽  
June L. Glover ◽  
Leslie D. Montgomery
Keyword(s):  
Blood Flow ◽  
Blood Volume ◽  
Supine Position ◽  
High Flow ◽  
Splanchnic Blood Flow ◽  
Low Flow ◽  
Postural Tachycardia Syndrome ◽  
Lower Body ◽  
Normal Flow ◽  
Postural Tachycardia

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°, 35°, and 70°. 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.

Decreased skeletal muscle pump activity in patients with postural tachycardia syndrome and low peripheral blood flow

2004 ◽  
Vol 286 (3) ◽  
pp. H1216-H1222 ◽  
Author(s):  
Julian M. Stewart ◽  
Marvin S. Medow ◽  
Leslie D. Montgomery ◽  
Kenneth McLeod
Keyword(s):  
Skeletal Muscle ◽  
Blood Flow ◽  
Blood Volume ◽  
Orthostatic Intolerance ◽  
Low Flow ◽  
Peripheral Blood Flow ◽  
Muscle Pump ◽  
Postural Tachycardia ◽  
Calf Blood Flow ◽  
Skeletal Muscle Pump

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 ± 1 vs. 39 ± 3 and 43 ± 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 ± 0.07 vs. 0.76 ± 0.07 and 0.80 ± 0.06). We found that blood flow was linearly correlated ( rp = 0.69) with calf circumference (used as a surrogate for muscle mass). Blood volume measurements were 2.2 ± 0.3 in low-flow POTS vs. 2.6 ± 0.5 in controls ( P = 0.17) and 2.4 ± 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.

scholarly journals Splanchnic hyperemia and hypervolemia during Valsalva maneuver in postural tachycardia syndrome

2005 ◽  
Vol 289 (5) ◽  
pp. H1951-H1959 ◽  
Author(s):  
Julian M. Stewart ◽  
Marvin S. Medow ◽  
Leslie D. Montgomery ◽  
June L. Glover ◽  
Mark M. Millonas
Keyword(s):  
Blood Pressure ◽  
Blood Flow ◽  
Blood Volume ◽  
Phase Ii ◽  
Valsalva Maneuver ◽  
Postural Tachycardia Syndrome ◽  
Peripheral Blood Flow ◽  
Control Subjects ◽  
Arterial Resistance ◽  
Postural Tachycardia

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.

scholarly journals Reduced body mass index is associated with increased angiotensin II in young women with postural tachycardia syndrome

2007 ◽  
Vol 113 (11) ◽  
pp. 449-457 ◽  
Author(s):  
Julian M. Stewart ◽  
Indu Taneja ◽  
Marvin S. Medow
Keyword(s):  
Body Mass Index ◽  
Blood Flow ◽  
Cardiac Output ◽  
Angiotensin Ii ◽  
Body Mass ◽  
Peripheral Blood ◽  
Postural Tachycardia Syndrome ◽  
Peripheral Blood Flow ◽  
Reduced Body ◽  
Postural Tachycardia

Altered peripheral haemodynamics, decreased cardiac output, decreased blood volume and increased AngII (angiotensin II) have been reported in POTS (postural tachycardia syndrome). Recent findings indicate that BMI (body mass index) may be reduced. In the present study, we investigated the hypothesis that reduced BMI is associated with haemodynamic abnormalities in POTS and that this is related to AngII. We studied 52 patients with POTS, aged 14–29 years, compared with 36 control subjects, aged 14–27 years. BMI was not significantly reduced on average in the POTS patients, but was reduced in patients with decreased peripheral blood flow. POTS patients were then subdivided on the basis of BMI, and supine haemodynamics were measured. There was no difference in blood volume or cardiac output once BMI or body mass were accounted for. When POTS patients with BMI <50th percentile were compared with controls, calf blood flow [1.63±0.31 compared with 3.58±0.67 ml−1·min−1·(100 ml of tissue)−1] and maximum venous capacity (3.87±0.32 compared with 4.98±0.36 ml/100 ml of tissue) were decreased, whereas arterial resistance [56±0.5 compared with 30±4 mmHg·ml−1·min−1·(100 ml of tissue)−1] and venous resistance [1.23±0.17 compared with 0.79±0.11 mmHg·ml−1·min−1·(100 ml of tissue)−1] were increased. Similar findings were also observed when POTS patients with BMI <50th percentile were compared with POTS patients with BMI >50th percentile. There was no relationship between blood flow, resistance or maximum venous capacity with BMI in control subjects. BMI was inversely related to plasma AngII concentrations in those POTS patients with decreased peripheral blood flow, consistent with cachectic properties of the octapeptide. Patients with low-flow POTS had decreased body mass, but decreased body mass alone cannot account for findings of peripheral vasoconstriction. In conclusion, the findings suggest that reduced body mass relates to increased plasma AngII.

scholarly journals Regional blood volume and peripheral blood flow in postural tachycardia syndrome

2004 ◽  
Vol 287 (3) ◽  
pp. H1319-H1327 ◽  
Author(s):  
Julian M. Stewart ◽  
Leslie D. Montgomery
Keyword(s):  
Blood Flow ◽  
Blood Volume ◽  
Supine Position ◽  
Peripheral Blood ◽  
Postural Tachycardia Syndrome ◽  
Peripheral Blood Flow ◽  
Control Subjects ◽  
Postural Tachycardia ◽  
Regional Blood Volume ◽  
Upright Tilt

Variants of postural tachycardia syndrome (POTS) are associated with increased [“high-flow” POTS (HFP)], decreased [“low-flow” POTS (LFP)], and normal [“normal-flow” POTS (NFP)] blood flow measured in the lower extremities while subjects were in the supine position. We propose that postural tachycardia is related to thoracic hypovolemia during orthostasis but that the patterns of peripheral blood flow relate to different mechanisms for thoracic hypovolemia. We studied 37 POTS patients aged 14–21 yr: 14 LFP, 15 NFP, and 8 HFP patients and 12 healthy control subjects. Peripheral blood flow was measured in the supine position by venous occlusion strain-gauge plethysmography of the forearm and calf to subgroup patients. Using indocyanine green techniques, we showed decreased cardiac index (CI) and increased total peripheral resistance (TPR) in LFP, increased CI and decreased TPR in HFP, and unchanged CI and TPR in NFP while subjects were supine compared with control subjects. Blood volume tended to be decreased in LFP compared with control subjects. We used impedance plethysmography to assess regional blood volume redistribution during upright tilt. Thoracic blood volume decreased, whereas splanchnic, pelvic, and leg blood volumes increased, for all subjects during orthostasis but were markedly lower than control for all POTS groups. Splanchnic volume was increased in NFP and LFP. Pelvic blood volume was increased in HFP only. Calf volume was increased above control in HFP and LFP. The results support the hypothesis of (at least) three pathophysiologic variants of POTS distinguished by peripheral blood flow related to characteristic changes in regional circulations. The data demonstrate enhanced thoracic hypovolemia during upright tilt and confirm that POTS is related to inadequate cardiac venous return during orthostasis.

scholarly journals Postural hypocapnic hyperventilation is associated with enhanced peripheral vasoconstriction in postural tachycardia syndrome with normal supine blood flow

2006 ◽  
Vol 291 (2) ◽  
pp. H904-H913 ◽  
Author(s):  
Julian M. Stewart ◽  
Marvin S. Medow ◽  
Neil S. Cherniack ◽  
Benjamin H. Natelson
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Blood Flow ◽  
Blood Volume ◽  
Peripheral Resistance ◽  
Impedance Plethysmography ◽  
Postural Tachycardia Syndrome ◽  
Peripheral Vasoconstriction ◽  
Postural Tachycardia ◽  
End Tidal

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 (PetCO2), 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°. Ten POTS patients demonstrated significant hyperventilation and hypocapnia (POTSHC) 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 POTSHC and was related to thoracic blood flow. Variability indexes suggested enhanced sympathetic activation in POTSHC compared with other subjects. The data suggest enhanced cardiac and peripheral sympathetic excitation in POTSHC.

scholarly journals Reduced central blood volume and cardiac output and increased vascular resistance during static handgrip exercise in postural tachycardia syndrome

2007 ◽  
Vol 293 (3) ◽  
pp. H1908-H1917 ◽  
Author(s):  
Julian M. Stewart ◽  
Indu Taneja ◽  
Marvin S. Medow
Keyword(s):  
Heart Rate ◽  
Cardiac Output ◽  
Blood Volume ◽  
Peripheral Resistance ◽  
Exercise Intolerance ◽  
Low Flow ◽  
Postural Tachycardia Syndrome ◽  
Central Blood Volume ◽  
Normal Flow ◽  
Postural Tachycardia

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 handgrip, systolic blood pressure increased from 112 ± 4 to 139 ± 9 mmHg in control, from 119 ± 6 to 143 ± 9 in normal-flow POTS, but only from 117 ± 4 to 128 ± 6 in low-flow POTS. Heart rate increased from 63 ± 6 to 82 ± 4 beats/min in control, 76 ± 3 to 92 ± 6 beats/min in normal-flow POTS, and 88 ± 4 to 100 ± 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.

Local vascular responses affecting blood flow in postural tachycardia syndrome

2003 ◽  
Vol 285 (6) ◽  
pp. H2749-H2756 ◽  
Author(s):  
Julian M. Stewart ◽  
Marvin S. Medow ◽  
Leslie D. Montgomery
Keyword(s):  
Blood Flow ◽  
Time Constant ◽  
Venous Hypertension ◽  
Low Flow ◽  
Postural Tachycardia Syndrome ◽  
Doppler Flowmetry ◽  
Control Subjects ◽  
Arterial Resistance ◽  
Postural Tachycardia ◽  
Peripheral Arterial

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 ± 0.2 vs. 4.4 ± 0.5 and 2.7 ± 0.4 ml · min–1 · 100 ml–1) but increased during leg lowering (1.2 ± 0.5 ml · min–1 · 100 ml–1) while decreasing in the others. Baseline peripheral arterial resistance was increased in LFP and decreased in HFP compared with control subjects (39 ± 13 vs. 15 ± 3 and 22 ± 5 mmHg · ml–1 · 100 ml · min) but decreased to 29 ± 13 mmHg · ml–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 ± 2 vs. 29 ± 4 and 28 ± 4 s; cutaneous time constant = 60 ± 25 vs. 149 ± 53 s in controls). Local blood flow regulation in low-flow POTS is impaired.

scholarly journals Angiotensin II type 1 receptor blockade corrects cutaneous nitric oxide deficit in postural tachycardia syndrome

2008 ◽  
Vol 294 (1) ◽  
pp. H466-H473 ◽  
Author(s):  
Julian M. Stewart ◽  
Indu Taneja ◽  
June Glover ◽  
Marvin S. Medow
Keyword(s):  
Nitric Oxide ◽  
Control Subject ◽  
Local Heating ◽  
Low Flow ◽  
Postural Tachycardia Syndrome ◽  
Ang Ii ◽  
Postural Tachycardia ◽  
Heat Response ◽  
And Control

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 (AT1R) 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°C and laser-Doppler flowmetry to assess NO-dependent conductance [percent maximum cutaneous vascular conductance (%CVCmax)] in 12 low-flow POTS patients aged 22.5 ± 0.8 yr and in 15 control subjects aged 22.0 ± 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 μg/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 ± 5 vs. 91 ± 7 %CVCmax; P < 0.001 vs. control). Losartan increased baseline flow in both POTS and control subjects (from 6 ± 1 to 21 ± 3 vs. from 10 ± 1 to 21 ± 2 %CVCmax; 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 ± 7 vs. 88 ± 6 %CVCmax; P = 0.48). NLA decreased both POTS and control subject heat responses to similar conductances (38 ± 4 vs. 38 ± 3 %CVCmax; P < 0.05 compared with predrug). The addition of NLA to losartan reduced POTS and control subject conductances compared with losartan alone (48 ± 3 vs. 53 ± 2 %CVCmax). The data suggest that the reduction in cutaneous NO-dependent vasodilation in low-flow POTS is corrected by AT1R blockade.

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