Liposome encapsulation attenuates hemoglobin-induced vasoconstriction in rabbit arterial segments

Journal of Applied Physiology
A S RudolphG Feuerstein

Abstract

Free hemoglobin (Hb) induces a potent vasoconstrictor response that may limit its therapeutic application as a red blood cell replacement. We have investigated whether encapsulation of stroma-free Hb (SFHb) or cross-linked Hb (alpha alpha-Hb) in liposomes modulates Hb vasoactivity in isolated blood vessels. Relaxation of rabbit thoracic vessels was measured before and after exposure to acellular SFHb, alpha alpha-Hb, and liposome-encapsulated SFHb or alpha alpha-Hb. SFHb and alpha alpha-Hb caused significant inhibition of carbachol-induced relaxation at 0.5 mg/dl, whereas encapsulation inhibited vessel relaxation at 30- to 60-fold higher Hb concentrations. The contractile response of rabbit ear arterial segments to electrical stimulation in the presence of acellular alpha alpha-Hb resulted in a 150% increase (EC150) in contractile amplitude at 0.23 mg/dl, whereas the EC150 for encapsulated alpha alpha-Hb was 13.7 mg/dl. Mechanistic studies of the vasoconstrictor activity of Hb demonstrated that acellular alpha alpha-Hb had no effect on norepinephrine release in the rabbit ear artery. In addition, neither acellular nor encapsulated alpha alpha-Hb preparations inhibited endothelial nitric oxide (NO) synthase activity isolated fro...Continue Reading

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Citations

Mar 4, 1999·Artificial Cells, Blood Substitutes, and Immobilization Biotechnology·J Szebeni, C R Alving
Mar 31, 2001·Artificial Cells, Blood Substitutes, and Immobilization Biotechnology·O O AbugoV W Macdonald
Jan 16, 2004·Critical Care Medicine·Jacques Creteur, Jean-Louis Vincent
Sep 24, 2004·Transfusion·Paul W Buehler, Abdu I Alayash
Mar 10, 2001·Transfusion·C P StowellR M Winslow
Aug 31, 2000·Critical Care Medicine·J CreteurJ L Vincent
Mar 4, 2010·Artificial Cells, Blood Substitutes, and Immobilization Biotechnology·Vibhudutta AwasthiR Towner
Apr 10, 2003·Journal of Veterinary Internal Medicine·William W Muir, Maxey L Wellman
Jun 25, 2005·Artificial Cells, Blood Substitutes, and Immobilization Biotechnology·A Chávez-NegreteM G Campos
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Aug 3, 2011·The Journal of Biological Chemistry·Ivan AzarovDaniel B Kim-Shapiro
Nov 21, 2002·Bioconjugate Chemistry·Shinji TakeokaEishun Tsuchida
Nov 20, 2003·Bioconjugate Chemistry·Yuji TeramuraEishun Tsuchida
Apr 4, 2009·Critical Care Clinics·Jacques Creteur, Jean-Louis Vincent

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