Protein-free phospholipid emulsion treatment improved cardiopulmonary function and survival in porcine sepsis.
Lipoprotein phospholipid (PL) plays a major role in neutralization of endotoxin. This study tested the hypothesis that prophylactic administration of a PL-enriched emulsion (PRE), which augments PL content of serum lipoproteins and neutralizes endotoxin in vitro, would preserve cardiovascular function and improve survival in porcine septic peritonitis. A control group was compared with low-, mid-, and high-dose treatment groups that received PRE by primed continuous infusion for 48 h. A fibrin clot containing live Escherichia coli 0111.B4 was implanted intraperitoneally 30 min after the priming dose. Survival increased in a dose-dependent manner and was correlated with serum PL. Infused PL was associated with high-density lipoprotein in the low-dose group and all serum lipoproteins at higher doses. Treatment significantly lowered serum endotoxin and tumor necrosis factor (TNF)-alpha, preserved cardiac output and ejection fraction, and attenuated increases in systemic and pulmonary vascular resistances. This study demonstrated that augmentation of lipoprotein PL via administration of PRE improved survival and offered a novel therapeutic approach to sepsis.
Goldfarb
Roy D
RD
Sections of Critical Care Medicine and Infectious Disease, Rush Medical College, Chicago, Illinois 60612, USA. roy.d.goldfarb@umdnj.edu
Parker
Thomas S
TS
Levine
Daniel M
DM
Glock
Dana
D
Akhter
Imran
I
Alkhudari
Azzam
A
McCarthy
Robert J
RJ
David
Eric M
EM
Gordon
Bruce R
BR
Saal
Stuart D
SD
Rubin
Albert L
AL
Trenholme
Gordon M
GM
Parrillo
Joseph E
JE
D000818:Animals; D002302:Cardiac Output / Q000187:drug effects*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004655:Emulsions / Q000494:pharmacology / Q000627:therapeutic use*; D004731:Endotoxins / Q000097:blood; D004927:Escherichia coli Infections / Q000188:drug therapy / Q000401:mortality; D005260:Female; D008075:Lipoproteins, HDL / Q000097:blood; D008297:Male; D010538:Peritonitis / Q000188:drug therapy / Q000401:mortality; D010743:Phospholipids / Q000097:blood / Q000494:pharmacology / Q000627:therapeutic use*; D012137:Respiratory System / Q000187:drug effects* / Q000382:microbiology; D018805:Sepsis / Q000188:drug therapy* / Q000401:mortality; D015996:Survival Rate; D013552:Swine; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D004655:Emulsions; D004731:Endotoxins; D008075:Lipoproteins, HDL; D010743:Phospholipids; D014409:Tumor Necrosis Factor-alpha