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doi:10.1111/j.1525-1594.2011.01296.x
210
aor_1296
210..223
(2)
METHODS
To implement the model, we used the O2 equilibrium curves (OECs) of HbRBC and propositus HbHBOC
with a PO2 resolution of 0.25 mm Hg in the range
0100 mm Hg. The OEC for HbRBC was obtained
assuming normal values for CO2, pH, and DPG
(P50 = 28 mm Hg) (4).The OECs for a high and a low
O2 affinity HbHBOC (MP4 and aaHb, P50 = 5 and
30 mm Hg, respectively) were provided from
Sangart, Inc. (San Diego, CA, USA). The OECs for
HBOCs with P50 = 20 and 40 mm Hg were obtained
from intrapolation/extrapolation of the mentioned
ones.
D[O2]a-v was calculated from Eq. (3) via an Excel
spreadsheet freely available from the authors. The
inputs are the OECs for HbRBC and HbHBOC and
their blood Hb concentrations [HbRBC] and
[HbHBOC]. The total O2 content (chemically bound to
Hb plus physically dissolved) in the arterial blood
([O2]a) at the selected PaO2 is calculated from the
OEC as:
(6)
211
RESULTS
212
O2 equilibrium curve
HBOC
0.6
0.4
Blood
50
PO2, mm Hg
75
6
4
100
10
50
5.0
75
100
40
28
20
10
5
P50RBC=28 mm Hg
[Hb]HBOC=2 g/dl
[Hb]RBC=8 g/dl
PaO2=95 mm Hg
6
4
75
P50HBOC, mm Hg
100
2.5
25
100
50
75
100
PvO2, mm Hg
C
O2 delivery
10
0
25
50
75
100
XT=0-100%
P50HBOC=5 mm Hg
P50RBC=28 mm Hg
[Hb]HBOC=0-8 g/dl
[Hb]RBC=16-0 g/dl
PaO2=95 mm Hg
8
6
4
PaO2, mm Hg
10
XT=50%
P50HBOC=5 mm Hg
P50RBC=28 mm Hg
[Hb]HBOC=2 g/dl
[Hb]RBC=8 g/dl
PaO2=55-95 mm Hg
8
6
4
95
85
75
65
55
2
0
O2 delivery
XT, %
[O2]a-v, mM
[O2]a-v, mM
50
75
PvO2, mm Hg
XT=50%
P50HBOC=5-40 mm Hg
8
[O2]a-v, mM
25
7.5
50
PO2, mm Hg
25
O2 delivery
10.0
25
XT, %
Total [O2], mM
0
25
O2 equilibrium curve
0.0
0
8
6
4
2
0
XT=50%
P50HBOC=5 mm Hg
P50RBC=28 mm Hg
[Hb]HBOC=0-6 g/dl
[Hb]RBC=8 g/dl
PaO2=95 mm Hg
0.2
0.0
0
[HbHBOC], g/dl
10
[O2]a-v, mM
Hb-O2 saturation
0.8
O2 delivery
P50, mm Hg
5
28
1.0
25
50
PvO2, mm Hg
75
100
25
50
75
100
PvO2, mm Hg
FIG. 2. O2 delivery at varying batch [Hb] and P50 in the HBOC
and oxygenation state. (A) Effect of varying [HbHBOC] in the range
08 g/dL in the circulation, which is equivalent to 012 g/dL in
the batch, at constant P50RBC, P50HBOC, [HbRBC], and PaO2 (see
inset). (B) Effect of varying P50HBOC in the range 540 mm Hg at
constant P50RBC, [HbHBOC], [HbRBC], and PaO2 (see inset). (C)
Effect of varying PaO2 in the range 5595 mm Hg at constant
P50RBC, P50HBOC, [HbHBOC], and [HbRBC] (see inset).
DISCUSSION
positive effect of increasing [Hb]HBOC is evident only
when P50HBOC is high. By contrast, PaO2 does not
appear as crucial because its value lies above the
PO2 range where O2 unloading by Hb might have
any influence.
Artif Organs, Vol. 36, No. 2, 2012
213
A
P50HBOC=5 mm Hg
P50HBOC=40 mm Hg
80
Kidneys
PvO2, mm Hg
70
60
Total
Brain
Legs
Heart
50
40
30
20
10
8 0
[HbHBOC], g/dL
[HbHBOC], g/dL
B
P50HBOC=5 mm Hg
P50HBOC=40 mm Hg
80
Kidneys
70
PvO2, mm Hg
60
50
Total
Brain
Legs
40
30
Heart
20
10
50
60
70
80
90
50
60
70
80
PaO2, mm Hg
PaO2, mm Hg
[Hb]HBOC=1 g/dL
[Hb]HBOC=4 g/dL
90
80
Kidneys
70
PvO2, mm Hg
60
40
Total
Brain
Legs
30
Heart
50
20
10
10
20
30
P50HBOC, mm Hg
40
10
20
30
40
P50HBOC, mm Hg
dard conditions, P50 is relatively constant but subjected to fluctuations arising in response to changes
in the mentioned allosteric effectors as well as
other factors that determine the actual P50 in vivo,
Artif Organs, Vol. 36, No. 2, 2012
214
including temperature, hydrostatic pressure, intracapillary Bohr effect, and varying RBC distribution (e.g., old and young RBCs coexisting in
the same blood stream) (6). Some of these changes
might, in principle, affect P50HBOC as well.
No loss of HBOC or RBC from the circulation,
or constant [HbHBOC] and [HbRBC], whereas Hb
extravasation is known to be a critical phenomenon in HBOC experimentation.
Negligible effects of nitric oxide (NO), an
endothelium-derived relaxing factor with a
number of effects in somatic cells. NO stimulates
soluble guanylate cyclase to form cyclic guanosine
monophosphate (cGMP), a messenger that mediates a large number of effects in the microcirculation in vivo. Current investigations also address the
hypothesis that Hb is a NO transporter (7) that
responds to changes in the Hb oxygenation state
(8) and helps NO export out of the RBC promoting local vasorelaxation and improving VO2 upon
Hb deoxygenation (9).
Constant RBC capillary transit time with negligible
blood flow autoregulation. However, recent work
addressed cerebral blood flow autoregulation as a
sensitive mechanism to tune the blood O2 transport
in response to the body/organ needs (10,11).
The described model cannot assess where exactly
O2 unloading in the capillary bed occurs, e.g., in the
precapillary area or elsewhere, while it is well
appreciated that O2 unloaded in the precapillary
contributes to vasoconstriction rather than tissue
oxygenation (12).
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