Microvascular effects following treatment with polyethylene glycol-albumin in lipopolysaccharide-induced endotoxemia

Nanae Hangai-Hoger, Parimala Nacharaju, Belur N. Manjula, Pedro Cabrales, Amy G. Tsai, Seetharama A. Acharya, Marcos Intaglietta

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Objective: To determine whether resuscitation with polyethylene glycol conjugated bovine serum albumin (2.5% weight/volume) infused at 16 mL/kg/hr (PEG-BSA-16) or at 24 mL/kg/hr (PEG-BSA-24) for 1 hr improves microcirculatory conditions in endotoxemia compared with dextran 70 (6% weight/volume) infused at 24 mL/kg/hr (Dex). Design: Prospective study. Setting: University research laboratory. Subjects: Male Golden Syrian hamsters. Interventions: Hamsters implemented with a skinfold window chamber were given an intravenous injection of lipopolysaccharide and resuscitated within 10 mins with Dex, PEG-BSA-16, or PEG-BSA-24. Measurements and Main Results: Hamsters were observed during 24 hrs after lipopolysaccharide injection. Systemic variables measured included mean arterial pressure, heart rate, and systemic arterial blood gas. Microvascular function was characterized by measuring vessel diameter; red blood cell velocity; functional capillary density (FCD); PO2 in arterioles, venules, and tissue; and perivascular nitric oxide concentration 6 hrs after lipopolysaccharide injection. At 6 hrs, animals with no treatment had the lowest FCD (6.7 ± 5.7% of baseline). PEG-BSA provided significantly improved microvascular conditions as shown by restoration of FCD. Recovery of FCD was related to improved microvascular flow and perivascular and tissue PO 2, normalization of shear rate, and decreased perivascular nitric oxide concentration. These effects were related to improved fluid retention using PEG-BSA-24 as evidenced by the significantly lower hematocrit at 24 hrs after resuscitation. Nitric oxide at 6 hrs after induction of sepsis achieved perivascular millimolar concentrations, which were reduced to normal values by PEG-BSA-24 treatment. At 6 hrs there were significant differences in FCD, tissue PO2, and perivascular nitric oxide concentration following PEG-BSA treatment by comparison with Dex treatment, although there were no differences in systemic variables between Dex and PEG-BSA groups. Conclusions: PEG-BSA produces improved microcirculatory conditions in the treatment of endotoxemia when compared with dextran 70.

Original languageEnglish (US)
Pages (from-to)108-117
Number of pages10
JournalCritical Care Medicine
Volume34
Issue number1
DOIs
StatePublished - Jan 2006

Fingerprint

Endotoxemia
Lipopolysaccharides
Albumins
Nitric Oxide
Dextrans
Resuscitation
Cricetinae
Therapeutics
Weights and Measures
Injections
Venules
Mesocricetus
Arterioles
Bovine Serum Albumin
Hematocrit
Intravenous Injections
Sepsis
Arterial Pressure
Reference Values
Erythrocytes

Keywords

  • Endotoxemia
  • Functional capillary density
  • Perivascular nitric oxide
  • Polyethylene glycol-albumin
  • Resuscitation
  • Tissue Po

ASJC Scopus subject areas

  • Critical Care and Intensive Care Medicine

Cite this

Microvascular effects following treatment with polyethylene glycol-albumin in lipopolysaccharide-induced endotoxemia. / Hangai-Hoger, Nanae; Nacharaju, Parimala; Manjula, Belur N.; Cabrales, Pedro; Tsai, Amy G.; Acharya, Seetharama A.; Intaglietta, Marcos.

In: Critical Care Medicine, Vol. 34, No. 1, 01.2006, p. 108-117.

Research output: Contribution to journalArticle

Hangai-Hoger, Nanae ; Nacharaju, Parimala ; Manjula, Belur N. ; Cabrales, Pedro ; Tsai, Amy G. ; Acharya, Seetharama A. ; Intaglietta, Marcos. / Microvascular effects following treatment with polyethylene glycol-albumin in lipopolysaccharide-induced endotoxemia. In: Critical Care Medicine. 2006 ; Vol. 34, No. 1. pp. 108-117.
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AU - Cabrales, Pedro

AU - Tsai, Amy G.

AU - Acharya, Seetharama A.

AU - Intaglietta, Marcos

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N2 - Objective: To determine whether resuscitation with polyethylene glycol conjugated bovine serum albumin (2.5% weight/volume) infused at 16 mL/kg/hr (PEG-BSA-16) or at 24 mL/kg/hr (PEG-BSA-24) for 1 hr improves microcirculatory conditions in endotoxemia compared with dextran 70 (6% weight/volume) infused at 24 mL/kg/hr (Dex). Design: Prospective study. Setting: University research laboratory. Subjects: Male Golden Syrian hamsters. Interventions: Hamsters implemented with a skinfold window chamber were given an intravenous injection of lipopolysaccharide and resuscitated within 10 mins with Dex, PEG-BSA-16, or PEG-BSA-24. Measurements and Main Results: Hamsters were observed during 24 hrs after lipopolysaccharide injection. Systemic variables measured included mean arterial pressure, heart rate, and systemic arterial blood gas. Microvascular function was characterized by measuring vessel diameter; red blood cell velocity; functional capillary density (FCD); PO2 in arterioles, venules, and tissue; and perivascular nitric oxide concentration 6 hrs after lipopolysaccharide injection. At 6 hrs, animals with no treatment had the lowest FCD (6.7 ± 5.7% of baseline). PEG-BSA provided significantly improved microvascular conditions as shown by restoration of FCD. Recovery of FCD was related to improved microvascular flow and perivascular and tissue PO 2, normalization of shear rate, and decreased perivascular nitric oxide concentration. These effects were related to improved fluid retention using PEG-BSA-24 as evidenced by the significantly lower hematocrit at 24 hrs after resuscitation. Nitric oxide at 6 hrs after induction of sepsis achieved perivascular millimolar concentrations, which were reduced to normal values by PEG-BSA-24 treatment. At 6 hrs there were significant differences in FCD, tissue PO2, and perivascular nitric oxide concentration following PEG-BSA treatment by comparison with Dex treatment, although there were no differences in systemic variables between Dex and PEG-BSA groups. Conclusions: PEG-BSA produces improved microcirculatory conditions in the treatment of endotoxemia when compared with dextran 70.

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