From the American Journal of Physiology – Heart and Circulatory , 30 May 2014.
Blunted Cerebral Blood Flow Velocity in Response to a Nitric Oxide Donor in Postural Tachycardia Syndrome (POTS)
Andrew Thomas Del Pozzi, Akash Pandey, Marvin S. Medow, Zachary R. Messer, Julian M. Stewart*
New York Medical College
* Corresponding author: New York Medical College firstname.lastname@example.org
Cognitive deficits are characteristic of postural tachycardia syndrome (POTS). Intact nitrergic nitric oxide (NO) is important to cerebral blood flow (CBF) regulation, to neurovascular coupling, and to cognitive efficacy. POTS patients often experience defective (NO) mediated vasodilation caused by oxidative stress.
We previously showed dilation of the middle cerebral artery (MCA) in response to a bolus administration of the NO donor sodium nitroprusside (SNP) in healthy volunteers. We hypothesized a blunted MCA response to SNP in POTS. Using combined transcranial-Doppler-ultrasound to measure CBF velocity (CBFv), and near-infrared spectroscopy (NIRS) to measure cerebral hemoglobin oxygenation while supine.
The responses of 17 POTS patients were compared with 12 healthy controls (ages 14-28). CBFv in POTS and control were not different at baseline (75 ± 3 vs. 71 ±2 cm • s-1 P = 0.31) and decreased to a lesser degree with SNP in POTS (to 71 ± 3 vs 62 ± 2 cm • s-1; P = 0.02). The changes in total and oxygenated hemoglobin (8.83 ± 0.45 and 8.13 ± 0.48 µmol/kg tissue) were markedly reduced in POTS compared to control (14.2 ± 1.4 and 13.6 ± 1.6 µmol/kg tissue), primarily due to increased venous efflux.
The data indicate reduced cerebral oxygenation, blunting of cerebral arterial vasodilation and heightened cerebral venodilation.
We conclude based on the current study outcomes decreased bioavailability of NO is apparent in the vascular beds resulting in a down regulation of NO receptor sites, ultimately leading to blunted responses to exogenous NO.
From Frontiers in Phsyiology, provisional pdf published on 3 June 2014. Full text available.
Original Research ARTICLE
Increases in Oscillatory Cerebral Blood Flow Velocity in Postural Tachycardia Syndrome
Marvin S. Medow(1), 2, Andrew T. Del Pozzi(1), Zachary Messer(1), Courtney Terilli(1) and Julian M. Stewart(1, 2*)
1) Pediatrics, New York Medical College, USA
2) Physiology, New York Medical College, USA
Decreased upright cerebral blood flow (CBF) with hyperpnea and hypocapnia is seen in a minority of patients with postural tachycardia syndrome (POTS). More often, CBF is not decreased despite upright neurocognitive dysfunction. This may result from time-dependent changes in CBF.
We hypothesized that increased oscillations in CBF occurs in POTS (N=12) compared to healthy controls (N=9), and tested by measuring CBF velocity (CBFv) by transcranial Doppler ultrasound of the middle cerebral artery, mean arterial pressure (MAP) and related parameters, supine and during 70o upright tilt.
Autospectra for mean CBFv and MAP, and transfer function analysis were obtained over the frequency range of 0.0078 to 0.4 Hz. Upright HR was increased in POTS (125±8 vs 86±2 bpm), as was diastolic BP (74±3 vs 65±3 mmHg) compared to control, while peripheral resistance, cardiac output, and mean CBFv increased similarly with tilt.
Upright BP variability (BPV), low frequency (LF) power (.04 – 0.13 Hz), and peak frequency of BPV were increased in POTS (24.3±4.1, and 18.4±4.1 mmHg2/Hz at .091 Hz vs 11.8±3.3, and 8.8 ± 2 mmHg2/Hz c at 0.071 Hz), as was upright overall CBFv variability, low frequency power and peak frequency of CBFv variability (29.3±4.7, and 22.1±2.7 [cm/s]2/Hz at .092 Hz vs 14.7±2.6, and 6.7 ± 1.2 [cm/s]2/Hz at 0.077Hz).
Autospectra were sharply peaked in POTS. LF phase was decreased in POTS (-14 ± 4 vs -25 ± 10 degrees) while upright. LF gain was increased (1.51 ± 0.09 vs 0.86 ± 0.12
[cm/s]/ mmHg) while coherence was increased (0.96 ± 0.01 vs 0.80 ± 0.04).
Increased oscillatory BP in upright POTS patients is closely coupled to oscillatory CBFv over a narrow bandwidth corresponding to the Mayer wave frequency. Therefore combined increased oscillatory BP and increased LF gain markedly increases CBFv oscillations in a narrow bandwidth. This close coupling of CBF to MAP indicates impaired cerebral autoregulation that may underlie upright neurocognitive dysfunction in POTS.