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


METHODS
Prospective study.


METHODS
University research laboratory.


METHODS
Male Golden Syrian hamsters.


METHODS
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.


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); P(O2) 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 P(O2), 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 P(O2), 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.
Hangai-Hoger
Nanae
N
Department of Bioengineering, University of California, San Diego, La Jolla, CA 92093-0412, USA.
Nacharaju
Parimala
P
Manjula
Belur N
BN
Cabrales
Pedro
P
Tsai
Amy G
AG
Acharya
Seetharama A
SA
Intaglietta
Marcos
M
D000818:Animals; D002196:Capillaries / Q000187:drug effects; D002417:Cattle; D006224:Cricetinae; D004195:Disease Models, Animal; D019446:Endotoxemia / Q000401:mortality / Q000628:therapy*; D008070:Lipopolysaccharides; D008297:Male; D008833:Microcirculation / Q000187:drug effects / Q000502:physiology*; D009569:Nitric Oxide / Q000032:analysis / Q000378:metabolism*; D010101:Oxygen Consumption / Q000502:physiology; D011092:Polyethylene Glycols / Q000494:pharmacology*; D011336:Probability; D012151:Resuscitation / Q000379:methods*; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D012710:Serum Albumin, Bovine / Q000494:pharmacology*; D015996:Survival Rate
D008070:Lipopolysaccharides; D012710:Serum Albumin, Bovine; D009569:Nitric Oxide; D011092:Polyethylene Glycols