Effects of Water and Glucose Drinks on Cardiovascular Function in Subjects With and Without Postprandial Hypotension
Condition: Autonomic Nervous System Diseases; Baroreflex Failure; Blood Pressure; Hypotension
MeSH terms: Nervous System Diseases; Autonomic Nervous System Diseases; Primary Dysautonomias; Hypotension
Study type: Interventional

Summary: 
      To determine whether the changes in blood pressure (BP) which occur following meals in normal
      people and patients who have substantial falls in BP after a meal postprandial hypotension
      (PPH)) are associated with changes in cardiac function. Eligible subjects who have been
      previously diagnosed with PPH will report to the Queen Elizabeth Hospital, on two occasions,
      following an overnight fast. Subjects will be cannulated and have a BP cuff placed around
      their upper arm. Following this, subjects will ingest either a drink containing 75 grams of
      glucose and 150mg of a C13 Acetate (which is metabolised and excreted in the breath, enabling
      noninvasive measurements of gastric emptying), made up to 300mL water, or on the other study
      day, 300mL water alone. The order of the study days will be randomised. Following the drink,
      for 3 hours, measurements will be taken at regular intervals of BP, heart rate, breath
      samples (on the study day with the Acetate only), blood samples (for measurement of blood
      glucose and gut hormones) and transthoracic echocardiography (TTE) (for assessment of end
      systolic and diastolic cardiac volume, cardiac output, cardiac contractility and diastolic
      function). After the 3 hours of measurements, the cannula will be removed and subjects will
      be offered lunch prior to leaving the department. Following lunch, on one study day, subjects
      will have their autonomic nerve function tested noninvasively, using an ECG.
    

Detailed description: 
      Subjects who meet the inclusion criteria will be required to attend the Queen Elizabeth
      Hospital, on two separate occasions, at 08:30h following an overnight fast (solids for 14
      hours and liquids for 12 hours) and abstaining from smoking for 12 hours prior to the study
      day. The order of the study days will be randomized using the online Random Integer Set
      Generator program (RANDOM.ORG).

      On each of the study days, subjects will be seated and have an intravenous cannula inserted
      into an antecubital vein in the arm for blood sampling and an automated blood pressure (BP)
      cuff (DINAMAP ProCare 100, GE Medical Systems, Milwaukee, WI, USA) placed around the opposite
      arm for measurements of BP (systolic and diastolic) and heart rate (HR).

      After a 15-minute rest period, subjects will consume a drink consisting of either 75g glucose
      and 150 mg of 13C-acetate made up to 300 ml with water, or 300 ml water, within 3 minutes (t
      = -3 - 0 minutes).

      BP and HR will be measured at 3 minute intervals during the 30-minute rest period prior to
      the drink (i.e. t = -30 - 0 minutes) and at 3 minute intervals from t = 0 - 180 minutes.

      Blood samples (~ 18ml) will be taken prior (t = -3 minutes) to the drink and then at t = 30,
      60, 90, 120 and 180 minutes for the subsequent measurement of blood glucose, serum insulin
      and incretin hormones. Samples will be stored at -70°C until analysed. Blood glucose will be
      determined immediately using a portable glucometer (Medisense Companion 2 meter, Medisense
      Inc, Waltham, USA).

      Following the 75g drink consisting of 75g glucose and 150 mg of 13C-acetate made up to 300 ml
      with water, at t = -3 minutes, and every 5 minutes between t = 0 - 60, followed by every 15
      minutes between t = 60 - 180, breath samples will be collected in sealed tubes for subsequent
      analysis of 13CO2 for measurement of gastric emptying.

      At t = -30 minutes and then at t = 30, 60, 90, 120 and 180 minutes, subjects will also
      undergo Transthoracic Echocardiogram (TTE) for assessment of (i) end-systolic and diastolic
      volumes (ii) cardiac output (iii) cardiac contractility, as assessed by measuring

        1. left ventricular dP/dt and

        2. overall wall motion by Doppler tissue imaging (DTI) of basal mitochondrial segments (iv)
           diastolic function, as assessed by measuring

      a) mitral inflow velocities b) DTI of mitral annulus c) left atrial size and d) pulmonary
      vein flow patterns Prior to each measurement, subjects will be allowed to rest for 15
      minutes, remaining still in a supine position.

      At t = 180 the cannulae will be removed and subjects will be offered a light lunch before
      leaving the department. The total amount of blood collected during the two visits is ~180 ml.

      On one of the study days after completion of these measurements autonomic nerve function will
      be assessed using standardised cardiovascular reflex tests. Parasympathetic function will be
      calculated by the variation (R - R interval) of the HR during deep breathing and the
      immediate HR response to standing ("30:15" ratio). Sympathetic function will be assessed by
      the fall in systolic BP in response to standing.
    

Intervention name(s): Glucose; Water
Intervention type(s): Other; Other
Intervention description(s): 75g glucose and 150 mg of 13C-acetate made up to 300 ml with water; 300ml water
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Single (Participant)
Primary purpose: Basic Science