Influence of inhibitors of the eicosanoid metabolism, of antagonists of the eicosanoids and of PAF on mortality assayed in three biochemically characterized shock models.
Experiments were carried out to lower the mortality (LD70-90) of rats in ovalbumin-induced anaphylactic (DA) shock and in endotoxin-induced (ET) shock, and of mice after injection of Platelet-activating Factor (PAF shock) comparing the effects of the cyclooxygenase (COX)-inhibitors aspirin (ASA), indomethacin, of the COX-/lipoxygenase (LOX)-inhibitors nordihydroguajaretic acid (NDGA), phenidone and X 86 (analogue of BW 755c), of the inhibitor of thromboxane (TX) synthesis HOE 944, of the TX-antagonist BM 13177, of the PAF-antagonist BN 52021 and of ketotifen. Ketotifen was strongly effective in DA shock, COX- and LOX-inhibitors only slightly. Combined COX- and LOX-inhibitors and BN 52021 showed good effects in the ET shock. Ketotifen was inefficacious. All the used substances influenced the PAF shock. The shock syndromes were biochemically characterized by determination of isocitratedehydrogenase (ICDH) activity, lactate, glucose, haematocrit, numbers of thrombocytes and leucocytes, TXB2 and 6-keto-Prostaglandin(PG)F1 alpha.
Bahr
T
T
Institute of Pharmacological Research - VEB of Pharmaceutical Combine GERMED, Berlin-Friedrichsfelde, GDR.
Schaper
U
U
Becker
K
K
Lueddeckens
G
G
Förster
W
W
Scheuch
D W
DW
Grupe
R
R
Göres
E
E
D000707:Anaphylaxis / Q000188:drug therapy / Q000401:mortality; D000818:Animals; D016861:Cyclooxygenase Inhibitors; D004195:Disease Models, Animal; D005260:Female; D016859:Lipoxygenase Inhibitors; D010972:Platelet Activating Factor; D051381:Rats; D011919:Rats, Inbred Strains; D012772:Shock, Septic / Q000188:drug therapy* / Q000401:mortality
D016861:Cyclooxygenase Inhibitors; D016859:Lipoxygenase Inhibitors; D010972:Platelet Activating Factor