Under baseline conditions for CD and autoregulation functionality (i.e., CD = 500 mm
−2 and Reg = 100%), an autoregulation plateau is predicted for incoming arterial pressure (
Pa) values of
Pa = 28 to 44 mm Hg in
Figure 2A (blue line). Without the ability to regulate flow (Reg = 0%), the autoregulation plateau disappears completely (
Fig. 2A, black line), and the predicted flow increases significantly with pressure, including for
Pa = 28 to 44 mm Hg.
Figure 2B shows the corresponding average downstream (post-capillary) oxygen saturation predicted by the model for the same conditions. When flow regulation mechanisms are fully functional (Reg = 100%), the plateau in flow between
Pa of 28 and 44 mm Hg corresponds to a similar plateau in oxygen saturation over that range (blue line), with values dropping only 13.6% from
Pa = 44 mm Hg to
Pa = 28 mm Hg. In the absence of regulation (Reg = 0%), there is a much larger (90.3%) drop in oxygen saturation for that same pressure range (
Fig. 2B). Outside the autoregulation range (i.e., for
Pa > 44 mm Hg or
Pa < 28 mm Hg), flow increases with pressure, as expected.
The impact of decreasing CD by 10% (450 mm
−2, black), 30% (350 mm
−2, red), and 50% (250 mm
−2, blue) is compared with the baseline case (500 mm
−2, green) in
Figure 3. As CD is decreased, the autoregulation plateau is translated to higher pressure values, and flow levels are increased (
Fig. 3A). Thus, significant decreases in CD lead to a loss in the autoregulation plateau in the normal physiological range of
Pa = 28 to 44 mm Hg. The effects of decreased CD on downstream oxygen saturation are shown in
Figure 3B; a loss in the ability to autoregulate leads to large decreases in oxygenation over that physiological pressure range. In particular, as
Pa is lowered from 44 mm Hg to 28 mm Hg, the change in downstream saturation is 13.6% for CD = 500 mm
−2 (as noted in
Fig. 2B); however, this change in saturation increases as CD is decreased: 16.5% at CD = 450 mm
−2, 36.4% at CD = 350 mm
−2, and 75.3% at CD = 250 mm
−2. This occurs despite all blood flow regulation mechanisms being active, which is the case for all simulations in
Figure 3.
Figure 4 demonstrates the impact of CD on mean tissue PO
2 levels downstream of the capillaries for autoregulation capacities (Reg) of 0%, 25%, 50%, and 100%. A 10% decrease in CD (from 500 mm
−2 to 450 mm
−2) yields a 5% decrease in tissue PO
2, whereas total impairment of regulation when CD = 450 mm
−2 yields an 8% decrease in tissue PO
2. If the CD is reduced by 10%
and regulation is impaired, PO
2 in the tissue is decreased by 12.4%. For larger decreases in CD, the gap in oxygenation widens between cases with full and impaired regulatory capacity. From the base case of CD = 500 to 250 mm
−2, the decrease in predicted downstream tissue oxygenation is 46.5% when Reg = 100%, 50.7% when Reg = 50%, 60.9% when Reg = 25%, and 96.3% when Reg = 0%.
Because elevated IOP is a significant risk factor for glaucoma, the impact of increasing IOP on model predictions was also investigated.
Figure 5 shows the predicted impact of increasing IOP from a baseline level of 15 mm Hg (blue) to an increased level of 25 mm Hg (red). In
Figure 5A, the predicted impact of increased IOP on flow as a function of pressure is shown. Higher IOP is predicted to shift the autoregulatory curve to the right (i.e., to higher levels of
Pa). The plateau is predicted to shift from
Pa = 28 to 44 mm Hg for IOP = 15 mm Hg to
Pa = 36 to 52 mm Hg for IOP = 25 mm Hg. The effects of this shift on downstream oxygen saturation are shown in
Figure 5B. As expected, the shift of the flow plateau effectively shifts the oxygenation curve to the right, as well. Importantly, over the physiological range of
Pa = 28 to 44 mm Hg, there is once again a loss in the autoregulatory plateau (in particular, for
Pa < 36 mm Hg). As a result, the downstream oxygen saturation is predicted to be about 75.7% lower at
Pa = 32 mm Hg with an IOP of 25 mm Hg than with an IOP of 15 mm Hg, and the saturation is predicted to be near 0 for
Pa = 28 mm Hg in the high IOP case.
To investigate the combined effects of elevated IOP and impaired blood flow regulation on tissue oxygenation, the model was simulated for a range of CD, with normal and high IOP, and with and without blood flow regulation.
Figure 6 shows the predicted mean tissue PO
2 level downstream of the capillaries with combinations of IOP = 15 and 25 mm Hg and Reg = 0% and 100% over a range of CD. With fully functioning regulation mechanisms, an increase in IOP from 15 to 25 mm Hg leads to a predicted decrease in downstream tissue PO
2 from 21.3 mm Hg to 20.6 mm Hg with a baseline CD of 500 mm
−2. If CD is decreased to 250 mm
−2, the downstream tissue PO
2 is predicted to decrease to 11.4 mm Hg when IOP = 15 mm Hg and to 6.7 mm Hg when IOP = 25 mm Hg. This gap in predicted oxygenation levels between the baseline and elevated IOP cases is much higher (41.3%) at CD = 250 mm
−2 compared to CD = 500 mm
−2 (3%). The combination of high IOP and fully impaired flow regulation (red dotted line in
Fig. 6) exacerbates the decreases in tissue PO
2 as CD is decreased, so that even a 10% reduction in CD (to 450 mm
−2) leads the predicted downstream tissue PO
2 to be just 4.6 mm Hg. Further reductions of CD to 350 and 250 mm
−2 yield predicted downstream tissue PO
2 values of 0.2 mm Hg and 0 mm Hg, respectively, in the absence of flow regulation and with elevated IOP.