Mw. Rooney et al., HEMODILUTION WITH OXYHEMOGLOBIN - MECHANISM OF OXYGEN DELIVERY AND ITS SUPERAUGMENTATION WITH A NITRIC-OXIDE DONOR (SODIUM-NITROPRUSSIDE), Anesthesiology, 79(1), 1993, pp. 60-72
Background: Hemodilution (HD) with oxyhemoglobin colloid (oxyHb) provi
des a greater arterial oxygen content (Ca(O2)) than HD with convention
al colloids; however, oxygen delivery (DO2) is essentially the same, b
ecause, in contrast to conventional HD, cardiac output (CO) is not aug
mented. This study seeks to elucidate the mechanism that limits CO dur
ing oxyHb-HD and to test whether infusion of a nitric oxide (NO) donor
would augment DO2, because oxyHb is known to inactivate in vitro endo
thelial-derived NO. Methods: Anesthetized dogs were isovolemically hem
odiluted with 10% oxyHb, 8% albumin, or 10% methemoglobin (weak NO ina
ctivator) to 20% hematocrit. After HD, sodium nitroprusside (SNP) was
titrated intravenously until decreases (> 10 mmHg) in mean aortic pres
sure (P(ao)) indicated the presence of exogenous NO. Systemic hemodyna
mics and regional blood flows (microsphere method) were measured. Resu
lts: Albumin-HD and metHb-HD produced typical HD-mediated responses: i
ncreased CO (63-65%), slight decreases (13-15%) in DO2, decreases in s
ystemic vascular resistance (SVR) proportional to the decreases (49-52
%) in blood viscosity of all three groups, and increased regional bloo
d flows (RBF). Responses to oxyHb-HD were atypical: CO and its determi
nants were not changed, DO2 decreased (23%) proportional to CaO2, and
SVR and most RBF were not changed except for a net redistribution of C
O to myocardium and skeletal muscle. In albumin-HD or metHb-HD, SNP (2
-5 mug . kg-1 . min-1) induced comparable decreases in mean P(ao) (29-
37%) and SVR (39-41%); however, CO, RBF, and DO2 were not affected. In
oxyHb-HD, exceptionally large doses of SNP (54 +/- 5 mug.kg-1.min-1)
decreased mean P(ao) only 19 +/- 1%; however, CO increased 78 +/- 5% a
nd decreases (61 +/- 3%) in SVR were slightly greater than viscosity r
eductions. Other determinants of CO were not affected. Most RBF increa
sed proportional to CO; there was, however, preferential distribution
to myocardium and skeletal muscle. Consequently, the augmented CO, and
CaO2 of oxyHb-HD, produced large increases in DO2, 77 +/- 5% from HD
alone and 43 +/- 3% from prehemodilution values. Conclusions: This stu
dy indicates that the limited CO and DO2 of oxyHb-HD resulted from opp
osing changes in two determinants of flow, i.e., reduced blood viscosi
ty and increased arterial resistance (vasoconstriction). The vasoconst
riction was not evident with metHb-HD and was reversed by the SNP infu
sion, indicating that oxyHb inactivated in vivo endothelial-derived NO
. The ability of the NO donor (SNP) to facilitate large viscosity-medi
ated increases in DO2 during oxyHb-HD is an important finding that cou
ld potentially render oxyHb colloids more useful than conventional col
loids, particularly for the individual with a compromised circulation
who would benefit from an increased oxygen supply.