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A new model for o 2 dependent ATP signaling between erythrocytes and capillary endothelium. Hasan Al-Taee Medical Biophysics Department Western University Wednesday April 4 th , 2012. Introduction. At the microvascular level, O 2 supply needs to be matched to O 2 demand. - PowerPoint PPT Presentation
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Hasan Al-Taee
Medical Biophysics Department
Western University
Wednesday April 4th, 2012
A NEW MODEL FOR O2 DEPENDENT ATP SIGNALING BETWEEN
ERYTHROCYTES AND CAPILLARY ENDOTHELIUM
INTRODUCTION
• At the microvascular level, O2 supply needs to be matched to O2 demand.
• Evidence that red blood cells (RBCs) release ATP when there is a decrease in O2 saturation (Bergfeld & Forrester, 1992; Jagger et al, 2001)
• Evidence that ATP applied to venules, capillaries or arterioles causes ascending vasodilation and increased vascular blood flow (Ellsworth et al, 2009)
MOTIVATION
• Existing model of microvascular flow regulation based on O2 dependent release of ATP by RBCs (Arciero et al, 2008)
• Implied:
• Capillaries not main site of RBC ATP-based flow regulation, despite being main site of blood-tissue O2 delivery
• Hematocrit- not RBC velocity or supply rate- is key factor in ATP signaling to endothelium by RBCs
OBJECTIVES
• Develop new model of O2 dependent ATP release in capillaries
• Determine if new model
• Increases ATP-based O2 supply regulation in capillaries
• Allows RBC velocity and supply rate to regulate flow at microvascular level
HYPOTHESES
• New model will demonstrate increased importance of RBC ATP release in capillaries when O2 saturation decreases
• New model will allow hematocrit, RBC velocity and RBC supply rate to regulate microvascular flow
METHODS
• Solve for ATP concentration in a single capillary
• One-dimensional steady state convection/reaction equation
• Change ATP release rate to function of rate of change of saturation with time: dS/dt=Vrbc*dS/dx
• Change control volume to plasma layer between RBC and vessel wall
• Plot analytical solutions using Matlab for varying conditions
EQUATIONS
• Arciero equation for ATP concentration C(x):
• New model for C(x):
VARIABLES
•ρ0 set to match asymptotic C in Arciero model for S=1 and dS/dx=0
•ρ1 set to match mean C(x) in Arciero model for baseline capillary conditions
PARAMETERS
• R0 = 1.4x10-9 mol s-1 cm-3
• R1= 0.891
• δ = 1 μm (plasma layer)
• D= 6x10-4 cm (diameter)
• HT=0.20xHf (hematocrit)
• Vrbc=0.025xVf (RBC velocity, cm/s)
• M0=1.5x10-4xMf (O2 consumption rate, ml O2 ml-1 s-1)
• ρ0=1.53x10-10 mol s-1 cm-3
• ρ1=8.0x10-9 mol cm-3
RESULTS
• Baseline case
• Increased oxygen consumption, baseline blood flow
• Increased oxygen consumption, increased velocity
• Increased oxygen consumption, increased velocity and hematocrit
DISCUSSION
• A decrease in oxygen saturation in capillaries will cause an increase in ATP release rate by RBCs
• This causes conducted signal along the capillary that will produce dilation of upstream arterioles and increased blood flow
• Larger decrease in saturation results in greater ATP release in capillaries in the new model, but not in Arciero model
• New model can maintain increase in hematocrit, velocity, and product (supply rate) via increased ATP, but Arciero model can only maintain smaller hematocrit increase
CONCLUSION
• New model, if correct, implies capillaries could be
main site of RBC ATP-based flow regulation and that
hematocrit and RBC velocity can both be regulated
via oxygen-dependent release of ATP by RBCs
ACKNOWLEDGMENTS
• Dr. Daniel Goldman
• Teaching Assistants
QUESTIONS ?
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