Reduced cerebral blood flow with orthostasis precedes hypocapnic hyperpnea, sympathetic activation, and postural tachycardia syndrome

Abstract

Hyperventilation and reduced cerebral blood flow velocity can occur in postural tachycardia syndrome (POTS). We studied orthostatically intolerant patients, with suspected POTS, with a chief complaint of upright dyspnea. On the basis of our observations of an immediate reduction of cerebral blood flow velocity with orthostasis, we hypothesize that the resulting ischemic hypoxia of the carotid body causes chemoreflex activation, hypocapnic hyperpnea, sympathetic activation, and increased heart rate and blood pressure in this subset of POTS. We compared 11 dyspneic POTS subjects with 10 healthy controls during a 70° head-up tilt. In POTS subjects during initial orthostasis before blood pressure recovery; central blood volume and mean arterial pressure were reduced (P<0.025), resulting in a significant (P<0.001) decrease in cerebral blood flow velocity, which temporally preceded (17±6 s; P<0.025) a progressive increase in minute ventilation and decrease in end tidal CO2 (P<0.05) when compared with controls. Sympathoexcitation, measured by muscle sympathetic nerve activity, was increased in POTS (P<0.01) and inversely proportional to end tidal CO2 and resulted in an increase in heart rate (P<0.001), total peripheral resistance (P<0.025), and a decrease in cardiac output (P<0.025). The decrease in cerebral blood flow velocity and mean arterial pressure during initial orthostasis was greater (P<0.025) in POTS. Our data suggest that exaggerated initial central hypovolemia during initial orthostatic hypotension in POTS results in reduced cerebral blood flow velocity and postural hypocapnic hyperpnea that perpetuates cerebral ischemia. We hypothesize that sustained hypocapnia and cerebral ischemia produce sympathoexcitation, tachycardia, and a statistically significant increase in blood pressure.

Keywords: autonomic nervous system; orthostatic intolerance.

Figure 1

Averaged respiratory data for all participants, (Control - black line, POTS - grey line) before and during a 10 min 70° head-up tilt. Expiratory Minute Volume (V_E) is expressed as liters per minute (L · min^-1), End tidal carbon dioxide (ETCO₂) as Torr, Respiratory Rate (Rate) as breaths per minute (bpm) and Tidal Volume (TV) expressed as milliliters (ml). * indicates different from control, P < 0.05.

Figure 2

Arterial blood pressure (AP) expressed as millimeters of mercury (mmHg), cerebral blood flow velocity (CBFv) as centimeters per second (cm · s^-1), Heart Rate (HR) as beats per minute (bpm), Expiratory Minute Volume (V_E) in liters per minute (L · min^-1), End Tidal Carbon Dioxide (ETCO₂) in Torr and Muscle Sympathetic Nerve Activity (MSNA) expressed as arbitrary units (AU) shown for a representative POTS patient before, during and after a 10 min 70° head-up tilt.

Figure 3

Hemodynamic data for all participants (Control - black line, POTS - grey line) before and during a 10 min 70° head-up tilt. Heart Rate (HR) is expressed as beats per min (bpm), Mean Arterial Pressure (MAP) as millimeters of mercury (mmHg), Cardiac Output (CO) as liters per minute (L · min^-1), and Total Peripheral Resistance (TPR) as millimeters of mercury per liter per minute (mm Hg · L · min^-1). * indicates difference from control, P < 0.05. # indicates overall effect different from control, P < 0.05.

Figure 4

Mean hemodynamic and respiratory data expressed as a percent (%) change from baseline before and during a 10 min 70° head-up tilt for all subjects (Control group - black line, POTS - grey line) showing Thoracic BV (Thorax), Mean Arterial Pressure (MAP), End Tidal Carbon dioxide (ETCO₂), changes in splanchnic BV (Splanchnic), changes in cerebral blood flow velocity (CBFv), and changes in total Muscle Sympathetic Nerve Activity (MSNA). * indicates difference from control, P < 0.05. # indicates overall effect different from control, P < 0.05.