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 ?