Hemodynamic responses to a hemoglobin bis-tetramer and its polyethylene glycol conjugate.
Transfusion
; 52(5): 974-82, 2012 May.
Article
em En
| MEDLINE
| ID: mdl-22070638
ABSTRACT
BACKGROUND:
The design of hemoglobin-based oxygen carriers (HBOCs) poses a significant challenge as clinical trials of many materials have reported adverse side effects that may come from the scavenging of the vasodilator nitric oxide (NO). A compensating reaction, reduction of endogenous nitrite by hemoglobin (Hb) and its derivatives, generates NO. Polyethylene glycol (PEG) conjugation of Hb enhances the rate of the reaction. STUDY DESIGN ANDMETHODS:
Hemoglobin bis-tetramers (BT) and their PEGylated derivative (BT-PEG) bind oxygen with a degree of cooperativity and also have significantly enhanced nitrite reductase activity compared to the native protein. Circulatory evaluation will test if the properties of BT and BT-PEG are reflected in their effects in vivo. BT and BT-PEG were evaluated as infusions into healthy wild-type (WT) and diabetic (db/db) mouse models. The effects were compared to infusions of murine Hb.RESULTS:
The materials were found not to cause significant increases in systemic blood pressure in either WT mice or db/db mice. The latter are highly sensitive to NO scavenging. Further hemodynamic measurements in WT mice indicate that while a slight increase in systemic vascular resistance (SVR) was observed after infusion of BT, the extent is not significant. No change in SVR from baseline was observed after infusion of BT-PEG.CONCLUSION:
The enlarged Hb derivatives do not evoke unfavorable circulatory responses that have been noted to result from infusion of Hb derivatives. These results suggest that a compromise between the P(50) , n(50) , and nitrite reductase activity of a Hb derivative can serve as the basis for producing HBOCs that can be tested for vasoactivity.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Polietilenoglicóis
/
Hemoglobinas
/
Hemodinâmica
Limite:
Animals
Idioma:
En
Ano de publicação:
2012
Tipo de documento:
Article