The Nobel prize awarded discovery of endothelia derived relaxation factor or EDRF, with the chemical formula NO, made it clear that within tissues micro-circulation is controlled by local factors. The resistance to the blood stream causes shear stress in the endothelium of feeding arteries releasing EDRF to the more distal branches. In this way arteries open when high resistance is met and, presumably, constrict when peripheral resistance is low, for instance, when arterioles open as part of vascular metabolic coupling.
Neuromon's cardiovascular model was expanded with a simulation of the hypothetical combined effect of arterial acceleration and EDRF. It is emphasised that for this purpose the model's parameters were fine tuned in order to meet its desired result: providing graphical imaging to theoretical considerations. The model could not be calibrated to experimental data, since data describing the relation between arterial acceleration and EDRF are yet unavailable.
Keeping this in mind the video below shows how the pressure wave resulting from the addition of a given stroke volume to the aorta spreads along the branches of the arterial tree without arterial acceleration and without regulation by EDRF. The added volume to the aorta pushes the blood forward into the branches of the arterial tree, resulting in a pulsatile wave that dampens along its course. The viscoelastic properties of the arterial tree prevent the pulsatile energy provided by heart contraction to fully reach into the periphery.
As we have seen, arterial acceleration may promote the pressure wave in reaching periphery, since the presumed shortlisting contraction within the smooth muscle layers of the arterial tree augments the pressure wave generated by heart contraction. Since arterial acceleration is thought to spread as a peristaltic wave along the branches of the arterial tree and distal arteries profit from tension already built up by proximal branches, its effect is expected to become greater towards periphery.
In the video below the effect of arterial acceleration is visible as an increase in pulsatility in the most distal branches. In addition, the steeper onset of the pressure wave is expected to promote the release of EDRF, symbolised by the colour yellow in this video. In the model the amount of EDRF release within a single arterial branch is arbitrarily calculated from the maximal change of pressure (dP/dt) in the capacitance one step more proximal. The EDRF is released into the next capacitance leading to an increase in its concentration, but because EDRF has a short half life the colouring of a capacitance to yellow is only short lived.
Local differences in metabolic activity may result in local differences in arteriolar resistance causing inhomogeneities in tissue perfusion. Likewise, the pressure within a tissue is often not evenly spread. This too may cause inhomogeneities in tissue perfusion.
The model was expanded by allowing the inclusion of local tissue pressure. Capacitances can be selected one by one and the model includes the effect of local tissue pressure by adjusting a slider up to 100mmHg max. The effect of this increase in tissue pressure is shown in the video below.
Arterial acceleration may improve the penetration of the pressure wave into tissues with unfavourable conditions, but it does not guarantee adequate blood supply. This is where EDRF comes into play. With the branches of the arterial tree EDRF helps to adjust local arterial diameter to local experienced shear stress.
In the simulation below every resistances adapts to the local EDRF concentration. If EDRF is high there is a pressure build up at stroke onset meaning that blood, despite arterial acceleration blood has difficulty flowing into the periphery. In the model a more distal resistance will be lowered allowing the blood to flow in more easily and reduce the build up of pressure in the more proximal capacitance. When there is little build up of pressure, EDRF will be low, and the model will increase the next resistance.
In the model the resistances are adjusted gradually, changing from one heart beat to another. Small bar graphs centred in each branch represent whether its resistance is higher or lower than its mean setpoint. Resistances are not adapted instantaneously but stepwise from one heart beat to another to avoid oscillations within the model. The bar plots can, therefore, be seen to rise (with their colour turning from green to red) symbolising an increase in resistance and be seen to lower (with their colour turning from red to green) symbolising a decrease in resistance. No bar plot is seen when the resistance is at its means setpoint.
Having seen how EDRF and arterial acceleration are likely to collaborate, another important aspect of EDRF must be emphasised: its intrinsic capacity to homogenise the blood flow within the branches of the arterial tree.
In the simulation below we show how EDRF adjusts resistances (that are not ideally preset) so that minimal pressure build up occurs at proximal branching nodes and blood is allowed to flow downstream with minimal interruption.
