Vascular response to infusions of a nonextravasating hemoglobin polymer

被引:91
作者
Matheson, B
Kwansa, HE
Bucci, E
Rebel, A
Koehler, RC
机构
[1] Univ Maryland, Sch Med, Dept Biochem & Mol Biol, Baltimore, MD 21201 USA
[2] Univ Maryland, Sch Dent, Dept Physiol, Baltimore, MD 21201 USA
[3] Johns Hopkins Med Inst, Dept Anesthesiol & Crit Care Med, Baltimore, MD 21205 USA
关键词
extravasation; zero linkage; blood substitute;
D O I
10.1152/japplphysiol.00191.2002
中图分类号
Q4 [生理学];
学科分类号
071003 ;
摘要
The clinical utility of cross-linked tetrameric hemoglobin solutions is limited by peripheral vasoconstriction thought to be due to scavenging of nitric oxide. In addition, transfusion of crude preparations of hemoglobin polymers can cause arterial hypertension. We tested the hypothesis that eliminating low-molecular-weight components from the polymer solution would prevent extravasation and its associated pressor response. A zero-link polymer of bovine hemoglobin was developed without chemical linkers left between the tetramers. Transfusion of unprocessed preparations of these polymers in rats resulted in appearance of the polymer in the renal hilar lymph. However, eliminating the low-molecular-weight components with a 300-kDa diafiltration resulted in an average hydrodynamic radius of 250 Angstrom and in undetectable levels of polymer in hilar lymph. Exchange transfusion in anesthetized rats and cats and in awake cats produced no increase in arterial pressure. In anesthetized cats, exchange transfusion with an albumin solution reduced hematocrit from 30 to 18%, increased cerebral blood flow, and dilated pial arterioles. In contrast, reducing hematocrit by transfusing the diafiltered polymer did not increase cerebral blood flow as pial arterioles constricted. These results are consistent with the hypothesis that the increase in arterial pressure associated with cell-free hemoglobin transfusion depends on hemoglobin extravasation. Constriction observed in the cerebrovascular bed with a nonextravasating hemoglobin polymer at low hematocrit is presumably a regulatory response to prevent overoxygenation at low blood viscosity.
引用
收藏
页码:1479 / 1486
页数:8
相关论文
共 30 条
[1]  
ABASSI Z, 1997, J LAB CLIN MED, V129, P580
[2]   Effect of cross-linked hemoglobin transfusion on endothelial-dependent dilation in cat pial arterioles [J].
Asano, Y ;
Koehler, RC ;
Ulatowski, JA ;
Traystman, RJ ;
Bucci, E .
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY, 1998, 275 (04) :H1313-H1321
[3]   ALBUMIN PERMEABILITY OF PERITUBULAR CAPILLARIES IN RAT RENAL CORTEX [J].
BELL, DR ;
PINTER, GG ;
WILSON, PD .
JOURNAL OF PHYSIOLOGY-LONDON, 1978, 279 (JUN) :621-640
[4]   Production and characteristics of an infusible oxygen-carrying fluid based on hemoglobin intramolecularly cross-linked with sebacic acid [J].
Bucci, E ;
Razynska, A ;
Kwansa, H ;
MathesonUrbaitis, B ;
OHearne, M ;
Ulatowski, JA ;
Koehler, RC .
JOURNAL OF LABORATORY AND CLINICAL MEDICINE, 1996, 128 (02) :146-153
[5]   A phase I study of oxidized raffinose cross-linked human hemoglobin [J].
Carmichael, FJL ;
Ali, ACY ;
Campbell, JA ;
Langlois, SF ;
Biro, GP ;
Willan, AR ;
Pierce, CH ;
Greenburg, AG .
CRITICAL CARE MEDICINE, 2000, 28 (07) :2283-2292
[6]  
CHATTERJEE R, 1986, J BIOL CHEM, V261, P9929
[7]   Elevation of plasma viscosity induces sustained NO-mediated dilation in the hamster cremaster microcirculation in vivo [J].
deWit, C ;
Schafer, C ;
vonBismarck, P ;
Bolz, SS ;
Pohl, U .
PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY, 1997, 434 (04) :354-361
[8]  
DIETZ NM, 1997, ANESTH ANALG, V85, P267
[9]   ZERO-LENGTH CROSSLINKING PROCEDURE WITH THE USE OF ACTIVE ESTERS [J].
GRABAREK, Z ;
GERGELY, J .
ANALYTICAL BIOCHEMISTRY, 1990, 185 (01) :131-135
[10]  
HARGENS R, 1977, AM J PHYSIOL, V233, pF269