TY - JOUR
T1 - Microvascular effects following treatment with polyethylene glycol-albumin in lipopolysaccharide-induced endotoxemia
AU - Hangai-Hoger, Nanae
AU - Nacharaju, Parimala
AU - Manjula, Belur N.
AU - Cabrales, Pedro
AU - Tsai, Amy G.
AU - Acharya, Seetharama A.
AU - Intaglietta, Marcos
N1 - Funding Information:
Supported, in part, by NIH USPHS grant Bioengineering Research Partnership R24-HL64395 and NIH grants R01-HL62354 and R01-HL62318 (MI), and HL-71064 and U.S. Army Grant PR023085 to J. Friedman.
PY - 2006/1
Y1 - 2006/1
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.
AB - 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.
KW - Endotoxemia
KW - Functional capillary density
KW - Perivascular nitric oxide
KW - Polyethylene glycol-albumin
KW - Resuscitation
KW - Tissue Po
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U2 - 10.1097/01.CCM.0000190623.97200.82
DO - 10.1097/01.CCM.0000190623.97200.82
M3 - Article
C2 - 16374164
AN - SCOPUS:29744466869
SN - 0090-3493
VL - 34
SP - 108
EP - 117
JO - Critical care medicine
JF - Critical care medicine
IS - 1
ER -