Sequential release of eicosanoids during endotoxin-induced shock in anesthetized pigs.
The release of eicosanoids during endotoxin shock was investigated in anesthetized pigs receiving 5 micrograms/kg Escherichia coli lipopolysaccharide (LPS) over 60 min into the superior mesenteric artery. TXB2, 6-keto PGF1 alpha and LTB4 concentrations in blood obtained from the superior mesenteric vein (SMV), right ventricle (RV) and aorta, during LPS infusion and an additional period of 2 h, were assessed along with hemodynamic variables, blood gases and pH and laboratory parameters. Half of the animals died within 30 min after termination of LPS infusion (non-survivors, n = 8), while the other half survived the experimental period of 3 h, though in a shock state (survivors, n = 9). The non-surviving pigs demonstrated progressively reduced cardiac output, hypotension and hypoperfusion in all organs. The surviving pigs demonstrated also a reduced cardiac output, which however was compensated by an elevated systemic vascular resistance resulting in a maintenance of arterial blood pressure. After exhausting this compensation the flow to non-vital organs increased and consequently arterial blood pressure was reduced resulting in hypoperfusion. In survivors a marked, though, transient increase was measured in concentrations of TXB2 and 6-keto PGF1 alpha level. A significant increase was measured in plasma concentration of LTB4 in SMV without any elevation in RV and aorta. LTB4 production started when prostanoid release had decreased. In contrast to survivors, no changes could be observed in eicosanoid release for non-survivors. A correlation was observed between systemic vascular resistance and TXB2 to 6-keto PGF1 alpha ratio.(ABSTRACT TRUNCATED AT 250 WORDS)
Mózes
T
T
Department of Pharmacology, Faculty of Medicine and Health Sciences, Erasmus University, Rotterdam, The Netherlands.
Zijlstra
F J
FJ
Heiligers
J P
JP
Saxena
P R
PR
Bonta
I L
IL
D015121:6-Ketoprostaglandin F1 alpha / Q000097:blood*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002560:Cerebrovascular Circulation / Q000187:drug effects; D004731:Endotoxins / Q000494:pharmacology*; D004926:Escherichia coli; D005260:Female; D006439:Hemodynamics / Q000187:drug effects*; D007975:Leukotriene B4 / Q000097:blood*; D012016:Reference Values; D012039:Regional Blood Flow / Q000187:drug effects; D012772:Shock, Septic / Q000097:blood / Q000503:physiopathology*; D013552:Swine; D013929:Thromboxane B2 / Q000097:blood*; D013997:Time Factors; D014655:Vascular Resistance / Q000187:drug effects
D004731:Endotoxins; D007975:Leukotriene B4; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha