Exercise Intolerance- the Exercise Pressor Reflex in POTS

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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 (17-29years) and 12 healthy subjects (18-27 years) 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 BP increased from 1124 to 1399 mmHg in control from 1196 to 1439 in normal flow POTS, but only from 1174 to 1286 in low flow POTS.  Heart rate increased from 636 to 824 bpm in control, 763 to 926 in normal flow POTS, and 884 to 1006 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 and blunted in normal flow POTS associated with abnormal splanchnic emptying. Cardiac output increased in control, was unchanged in low flow and was attenuated in normal flow POTS. Total peripheral resistance was increased compared to control in all POTS. The exercise pressor reflex is attenuated in low flow POTS. While increased cardiac output and central blood volume characterizes controls, increased peripheral resistance with blunted or eliminated i central blood volume increments characterize POTS and may contribute to exercise intolerance.

 

 




 

Table 2 Heart Rate and Blood Pressure Variability

 

Baseline

1 min

2 min

1&2 min

Recovery

Total HRV Power (TP, ms2/Hz)

Control

Low Flow

Normal Flow

 

3213836

837162

1689380

1683714

1080366

2273565

 

22071156*

1004276

1973463

 

2156895*

980299

2094275

 

3245906

1682616*

2120503

Low Frequency (LF, 0.04-0.15Hz) HRV Power  (ms2/Hz)

 Control

Low Flow

Normal Flow

 

1071310

19844

555124

 

562279*

415169*

468107

 

1061710

29461

573133

 

769326

301108

38365

 

1197367

593194*

768193

High Frequency (HF, 0.2-0.5 Hz) HRV Power (ms2/Hz)

 Control

Low Flow

Normal Flow

 

1476498

21664

589204

 

827417

485197*

1567435*

 

847389

556181*

1205338*

 

843377

407127*

845207

 

1546423

898390*

1093276*

LF/HF Ratio

Control

Low Flow

Normal Flow

 

0.90.19

1.180.21

1.33.18

 

0.80.17

0.87.16

0.38.04*

 

1.76.63*

1.1.29

0.83.26

 

1.02.31

0.81.11

0.62.11

 

1.120.20

1.060.31

1.090.17

Total BPV Power (mmHg2/Hz)

Control

Low Flow

Normal Flow

 

8.42.0

10.22.0

12.52.4

 

6.80.8*

7.12.0*

12.88

 

9.81.5*

6.91.3*

13.44.3

 

9.51.6

8.02.0

10.62.6

 

10.02.3

6.72.1

7.51.8

Transfer Coherence

Control

Low Flow

Normal Flow

 

0.760.10

0.36.05

0.7.04

 

0.41.06*

0.3.07*

0.3.06*

 

0.26.05*

0.30.07*

0.22.06*

 

0.34.05*

0.23.06*

0.24.04*

 

0.42.06*

0.17.04*

0..20.05*

Transfer Magnitude (gain/ms/mmHg)

Control

Low Flow

Normal Flow

 

 

 

182

82

132

 

 

 

112*

12.3

21.6*

 

 

 

82*

133*

174*

 

 

 

102*

1910

81*

 

 

 

112*

18.59*

123

Transfer Phase (Degrees)

Control

Low Flow

Normal Flow

 

 

2412

538

505

 

8046*

129.34*

169.32*

 

9040*

14033*

17137*

 

8842*

13224*

17025*

8017*

9224*

210198

                       (*p<0.05 compared to baseline, =p<0.05 different from control.)

 

 

 

 

 

 

 

 

 

 

 

 

 1. The left panels show representative heart rate (upper panel) and blood pressure (lower panel) from a control subject during static handgrip.  The right panels show corresponding representative heart rate (upper panel) and blood pressure (lower panel) from a low flow POTS subject. Baseline heart rate is increased in the POTS patient compared to control. Heart rate and blood pressure increases with handgrip are attenuated in the POTS patient.

 

 

 

 

 

The left panels show percent changes in heart rate (upper panel) and blood pressure (lower panel) averaged over all subjects. Control subjects are in black, low flow POTS in red, normal flow POTS in green. Percent changes are shown after 1 and 2 minutes of handgrip and during the recovery period. There is an attenuation of the increase in heart rate and blood pressure for low flow POTS. *=P<0.05 compared to control subjects.

 

 

  

 

The figure shows percent changes from baseline in thoracic, splanchnic, pelvic, and calf blood volumes during handgrip averaged over all subjects at 1 minute and 2 minutes after starting handgrip and during recovery. Central thoracic blood volume increases for control but in neither POTS group at 1 minute and remains different from control at 2 minutes of handgrip and during recovery. Increased cardiac volume corresponds to a decrease in splanchnic volume which is absent in POTS. *=P<0.05 compared to control.

 

 

The figure shows percent changes in segmental blood flow. From top down changes in thoracic, splanchnic, pelvic and leg (calf) are shown in order. Blood flow increases for the central thoracic (CO) in healthy controls but not in POTS at 1 minute of handgrip. CO does increase in normal flow POTS patients at the second minute of handgrip. Percent change in splanchnic blood flows are increased in POTS, while pelvic and calf  segments are variably affected in POTS subgroups. *=P<0.05 compared to control.

 

The figure shows percent changes in segmental arterial resistance. From top down changes in thoracic, splanchnic, pelvic and calf are shown in order. Total peripheral resistance (thoracic resistance) was mildly increased in control subjects but markedly increased in POTS patients. This was generally  associated with an increase in pelvic and calf resistance in POTS compared to control. *=P<0.05 compared to control.

 

 

 

Blunted Heart Rate and Blood Pressure Response to Static Handgrip in Low Flow POTS  Our results show a significantly attenuated change in blood pressure and heart rate in low flow POTS patients only. These patients have evidence for sympathetic over-activation at rest with blunted changes observed in response to sympathetic stimuli particularly affecting the distribution and redistribution of blood volume (see below). Typically, while low flow patients are normotensive they share many phenotypic features of circulatory insufficiency including pallor, baseline tachycardia, peripheral vasoconstriction and reduced central blood volume with blunted responses to subsequent sympathetic stimuli.  

The Increase in Central Blood Volume is Blunted in POTS The normal increase in central blood volume during the exercise pressor reflex is abolished in low flow POTS patients and attenuated in normal flow POTS. In general there appears to be an overall reduction in regional blood volume redistribution in low flow POTS.

Normal flow POTS patients have blunting of blood volume redistribution that relates to selective pooling in the splanchnic circulation. This limits the increases in central blood volume during handgrip. Similar limitation of central blood volume occurs during orthostatic stress.

Total Peripheral Resistance rather than Cardiac Output Drives Regional Blood Volume The most important new finding in this study is that the exercise pressor reflex  produces a smaller pressor response in low flow POTS patients and that the mechanism of the pressor response is shifted from the increased cardiac output and central blood volume observed in control subjects to increased vasoconstriction and peripheral resistance. Specifically, in low flow POTS, the cardiac output component is essentially abolished and the pressor response is completely driven by increased peripheral resistance. In normal flow POTS vasoconstriction is more selective and is deficient within the splanchnic regional circulation. We have presented evidence for sympathoexcitation in POTS  and others have presented measurements of increased sympathetic nerve activity with blunting of responses to diverse stimuli. We propose that the data shown here support the theories that low flow POTS patients have inappropriate sympathetic and adrenergic activation possibly driven by central nervous system mechanisms controlling sympathetic outflow, while normal flow POTS patients have reflex peripheral sympathetic activation produced by selective splanchnic blood flow deficits.  

Baroreflex regulation of Heart Rate during Handgrip  (Cardiovagal Regulation): As noted previously, HRV technique alone or combined with measurement of blood pressure variability primarily estimates parasympathetic control of heart rate.  The difficulty in interpreting sympathetic change is somewhat improved by using the low frequency to high frequency ratios. In that regard, it is interesting that overall HRV power and low frequency power, although decreased compared to control in low flow POTS patients,  is sustained or even increased during exercise. This is different from results from control patients in whom heart rate variability and by extension baroreflex gain are reduced by the metaboreflex  with similar findings in animal models. Sustained sympathetic effects on the heart and are consistent with sustained sympathetic cardiac contractility. In support, low flow POTS patients have markedly increased cardiac afterload, no increase in cardiac preload and sustained cardiac output suggesting increased contractility. Therefore, it may be reasonable to infer that cardiac sympathetic innervation remains relatively intact in POTS even though baroreflex gain may be reduced.

On the other hand, cardiovagal coherence is inadequate in low flow POTS at all times. This indicates uncoupling between blood pressure and heart rate regulation

The Exercise Pressor Reflex in POTS - Central Sympathetic Activation The shift from a cardiac output driven exercise pressor response to an arterial resistance-driven pressor response is similar to observations made in congestive heart failure. In heart failure, baroreflexes are markedly impaired  with reductions in both sympathetic and cardiovagal baroreflex sensitivities.  As a result the ability of the arterial baroreflex to buffer the muscle metaboreflex is severely attenuated  . In low flow POTS, the baroreflexes are also impaired  with reductions in both sympathetic and cardiovagal baroreflex sensitivities. The arterial baroreflex buffers the vasoconstriction from the muscle metaboreflex and mechanoreflex comprising the exercise pressor reflex by reducing this peripheral vasoconstriction.  Arguing by analogy, recent data concerning heart failure indicate an important role for increased angiotensin II and decreased neuronal nitric oxide activity in attenuating the baroreflex. Increased angiotensin II and reduced nitric oxide are features of low flow POTS.

 

 
 
 

 


Up
Exercise Intolerance- the Exercise Pressor Reflex in POTS
Skeletal Muscle Pump
Normal Leg Venous Capacitance
Postural Neurocognitive
Splanchnic Pooling in Normal Flow POTS
Nitric Oxide Dysfunction in Low Flow POTS
Angiotensin-II in POTS
Decreased Upright Cerebral Blood Flow and Cerebral Autoregulation in POTS
Postural Hyperpnea
Nitric Oxide is Decreased in Angiotensin-II dependent Low flow POTS but increased along with Splanchnic pooling Neuropathic POTS
Local Vascular Responses in POTS
Microvascular Filtration in High Flow POTS
POTS as Thoracic Hypovolemia