Table 2. Optimized model parameters.
The 20 most influential model parameters on oxCOX and TOI included in the optimization are shown with initial values and ranges before optimization. Parameters are ordered from top to bottom according to their sensitivity to oxCOX and TOI, respectively.
| oxCOX parameters | Unit | Initial value |
Range | |
|---|---|---|---|---|
| oxCOX signal | Oxidized cytochrome-c-oxidase assessed by NIRS | |||
| CuA,o,n | Normal concentration of oxidized CuA | mM | 0.066 | 0.046–0.085 |
| Volmit | Fraction of brain tissue volume that is mitochondria | - | 0.067 | 0.054–0.080 |
| klk2 | Constant controlling depending of leak rate Llkon Δp | mV−1 | 0.038 | 0.030–0.456 |
| Δpn | Normal value of Δp (proton-motive force) | mV−1 | 168.611 | 118.028–219.194 |
| NADn/NADHn | Normal NAD+/NADH ratio | - | 9 | 0.1–20 |
| k1,n | Forward reaction rate for CuAreduction at normal Δp/NADH | s−1 | 8.3 | 5.810–10.790 |
| ck1 | Parameter controlling sensitivity of k1to Δp | mV−1 | 0.01 | 0.008–0.012 |
| Tmax,0 | Maximal muscular tension under normal regulatory stimulus | mmHg cm | 2.11 | 1.477–2.743 |
| vCO2,n | Normal filtered carbon dioxide partial pressure | mmHg | 40 | 28–52 |
| ϕ | Oxygen concentration at half-maximal saturation | mM | 0.036 | 0.029–0.043 |
| rm | Vessel radius at which muscular tension is maximal | cm | 0.027 | 0.022–0.032 |
| kunc | Parameter simulating effect of uncouplers to the system | - | 1 | 0.8–1.2 |
| COXtis | Concentration of COX in tissue | mM | 0.006 | 0.004–0.007 |
| Llk0 | Constant controlling the depending of the leak rate Llk on Δp | mM s−1 | 0.004 | 0.003–0.006 |
| ptot | Total protons moved out of mitochondrial matrix | - | 20 | 18–20 |
| Kσ | Parameter controlling sensitivity of σe to vessel radius | - | 10 | 7–13 |
| CVinh | Control parameter representing action of CCO inhibitors | - | 1 | 0.8–1.2 |
| vu,n | Normal filtered demand | - | 1 | 0.7–1.3 |
| h0 | Thickness of blood vessel walls at which radius is r0 | cm | 0.003 | 0.002–0.004 |
| Pic | Intracranial pressure | mmHg | 9.5 | 7–11 |
| TOI parameters | Unit | Initial value |
Range | |
| TOI signal | Tissue oxygenation index assessed by NIRS | |||
| Tmax,0 | Maximal muscular tension under normal regulatory stimulus | mmHg cm | 2.109 | 1.477–2.743 |
| D02 | Diffusion rate for oxygen between capillaries and mitochondria | s−1 | 0.842 | 0.589–1.094 |
| rt | Radius in the muscular tension relationship | cm | 0.018 | 0.014–0.022 |
| ϕ | Oxygen concentration at half-maximal saturation | mM | 0.036 | 0.029–0.043 |
| vCO2,n | Normal filtered carbon dioxide partial pressure | mmHg | 40 | 28–52 |
| rn | Normal effective blood vessel radius | cm | 0.019 | 0.015–0.022 |
| Kσ | Parameter controlling sensitivity of σe to vessel radius | - | 10 | 7–13 |
| Volv | Relative venous blood volume | - | 0.75 | 0.525–0.975 |
| klk2 | Constant controlling depending of leak rate Llkon Δp | mV−1 | 0.038 | 0.030–0.456 |
| vO2,n | Normal filtered capillary oxygen concentration | mM | 0.064 | 0.045–0.084 |
| kaut | Overall functioning of autoregulatory response | - | 1 | 0–1 |
| NADn/NADHn | Normal NAD+/NADH ratio | - | 9 | 0.1–20 |
| vu,n | Normal filtered demand | - | 1 | 0.7–1.3 |
| σe,0 | Parameter in elastic tension relationship | mmHg | 0.143 | 0.114–0.171 |
| RCO2 | Autoregulatory reactivity to carbon dioxide | - | 2.2 | 1.5–2.9 |
| ε0NADH | Standard redox potential for NADH | mV | −320 | −384−-256 |
| Δpn | Normal value of Δp (proton-motive force) | mV−1 | 168.611 | 118.028–219.194 |
| COXtis | Concentration of COX in tissue | mM | 0.006 | 0.004–0.007 |
| Llk0 | Constant controlling depending of leak rate Llk on Δp | mM s−1 | 0.004 | 0.003–0.006 |
| p2 | Proton cost of reaction reducing a3 | − | 4 | 2.8–5.2 |