Computational Models of Cardiovascular Function for Analysis of Post-Flight Orthostatic Intolerance

Transcription

1 Computational Models of Cardiovascular Function for Analysis of Post-Flight Orthostatic Intolerance Thomas Heldt, Eun B. Shim, Roger D. Kamm, and Roger G. Mark Massachusetts Institute of Technology

2 Background: Cardiovascular problems following spaceflight have been encountered since the Mercury missions Drastically increased heart rates have been noted in upright tilt-table testing during the Gemini missions Post-spaceflight orthostatic intolerance was noted in Apollo astronauts for up to 3 days after landing Skylab mission explored human physiology during long-term space missions Spacelab provided a framework for studying human physiology with emphasis on various organs systems

3 Problems: High variability in individual responses Small number of subjects studied Environmental effects unclear Conflicting experimental observations Computational Models might help

4 Rationale for Modeling: Provides rational framework to interpret experimental results and test hypotheses Aids in predicting benefits of specific countermeasures

5 Goals: Simulate the short term (10-15 mins) response to orthostatic stress in normals and microgravity adapted individuals Test hypotheses concerning mechanisms of orthostatic intolerance Simulate effects of countermeasures

6 The Hemodynamic Model: Thirteen compartment lumped-parameter hemodynamic model R i R o P i V( P) P bias Pressure Variations From:Gauer et al. in: Handbook of Physiology.

7 The Hemodynamic Model: Pulm. Veins Pulm. Art. Left Ventr. Right Ventr. Upper Body Sup. VC Syst. Art. Kidneys Splanchnic Abd. Veins Inf. VC Lower Body

8 Control System: Arterial Baroreflex Cardiopulmonary reflex; s s,p s s Individual gains adjustable Effector mechanisms: heart rate, venous tone, cardiac contractility, and arteriolar resistance P AT P CS

9 Control System:

10 Control System: P = P trans P set p: 0 1 sec P eff s: sec Heart Rate Contractility Venous Tone Art. Resistance P eff (t-k) {α p(k) + β s(k)} dk

11 Model Performance: Parameter Model Normal Value* Pressures (mm Hg) LVP 131/6 130/7 ABP 130/80 130/70 CVP 5/3 7/5 RVP 28/1 24/4 Stroke Vol. Ind (ml/beat per m 2 ) Cardiac Index (l/min per m 2 ) * Based on: Hurst s The Heart, RW Alexander (ed.), vol.1, 9 th ed.

12 Tilt/Stand Test - Physiology: Rapid translocation of blood into dependent veins Reduction of hydrostatic pressure at carotid sinus Neural reflexes mediate initial circulatory response Extravasation of plasma volume into interstitial compartment Renal-endocrine mechanisms contribute during prolonged orthostatic stress

13 Tilt Table/Stand Test Simulation: Account for fluid shifts into dependent venous compartments by varying bias pressures at C LL1, C LL2, C SP, and C AB P bias = P 0 sin(α(t)) Account for blood plasma leakage from capillaries by reducing overall blood volume over time Account for gravitational effect on sensed carotid sinus pressure P CS = ρgh sin(α(t))

14 Stand-Test Simulation: Pre-Spaceflight ABP 60 HR Simulation ABP HR

15 Stand-Test Simulation: Mean Arterial Pressure (mmhg) Heart Rate (beats/min) Angle of Tilt (degrees) Angle of Tilt (degrees)

16 Stand-Test Simulation: 0-10 Stroke Volume (ml) Angle of Tilt (degrees)

17 LBNP Physiology: Negative external pressure causes venous pooling in lower extremities Neural reflexes mediate initial circulatory response Extravasation of plasma volume into interstitial compartment Renal-endocrine mechanisms contribute during prolonged LBNP-stress

18 LBNP - Simulation: Apply appropriate bias pressure on C LL1 and C LL2 : P bias1,2 = 0 for t < t 0 P 0 for t t 0 Apply reduced bias pressure to abdominal great veins: P bias4 = ε P 0 for 0 < ε < 0.5 Account for blood plasma leakage from capillaries by reducing overall blood volume

19 LBNP Simulation: 8 12 Mean Arterial Pressure (mmhg) Heart Rate (beats/min) Level of LBNP (mmhg) Level of LBNP (mmhg)

20 LBNP Simulation cont d: 0-10 Stroke Volume (ml) Level of LBNP (mmhg)

21 Testing of Hypotheses: Simulate response to orthostatic stress test for different sets of hemodynamic and/or control parameters Compare simulation to experimental observation based on some measure Repeat simulation with different sets of parameters until best fit is achieved

22 Astronaut Stand Tests: 140 Pre-Spaceflight 150 ABP 60 HR Post-Spaceflight ABP 60 HR 20 Source of data: J. Fritsch-Yelle, Johnson Space Center 50

23 Stand-Test Simulation: Pre-Spaceflight ABP 60 HR Simulation ABP HR

24 Total Blood Volume Testing Hypotheses Heart Rate Gain HR Post-Spaceflight HR HR Resistance Gain Venous Tone Gain HR HR 50 Source of data: J. Fritsch-Yelle, Johnson Space Center 50

25 Combining Hypotheses Hypovolemia Venous Feedback Arteriolar Feedback 150 HR 50 Source of data: J. Fritsch-Yelle, Johnson Space Center

26 Countermeasures: In-flight exercise In-flight LBNP Fluid Loading Mineralocorticoids Midodrine Short arm centrifuge (artificial gravity)

27 Simulation of Midodrine 150 HR 50 Source of data: J. Fritsch-Yelle, Johnson Space Center