The endotoxin shock response of Beagle dogs, characterized by profound hypotension and progressive fatal disseminated intravascular coagulation (DIC) was compared in anaesthetized normal dogs and in dogs previously decomplemented with purified cobra venom factor. The hypotension and the early thrombocytopenia were abolished in the decomplemented group, while the subsequent DIC was greatly ameliorated. Factor VII was apparently activated in decomplemented dogs but consumed in normal dogs. An observation as yet to be defined in relation to the shock syndrome was that dog platelets lcst their collagen aggregation throughout the period of total decomplementation. It is suggested that complement activation is a major requirement for the full expression of fatally progressive DIC in endotoxin shock and that the activation of the coagulation system occurs, at least in part, via the extrinsic pathway.The mortality rate in patients with Gram-negative septicaemia and associated hypotension is reported to be 5o-8o% in recently reviewed series (Corrigan &Jordan, 1970). A large proportion of these patients have evidence of disseminated intravascular coagulation (DIC) and despite heparin therapy the mortality remains high in this subgroup. The agent thought to be responsible for the hypotension and DIC is the lipopolysaccharide (endotoxin) component of the bacterial cell wall. The many experimental studies and clinical observations have tended to concentrate on the haemodynamics and blood coagulation (Gilbert, 1960;Beller, 1969), yet the precise way in which endotoxin causes its pathogenic effects is not known. Relatively little attention has been paid to the role of the complement system although it is now well recognized that endotoxin is a powerful activator of Complement (McKay, 1973 ;Gewurz et al, 1968Gewurz et al, , 1970Gilbert & Braude, 1962) and that there is a relationship, as yet only partly defined, between the complement and coagulation systems (Zimmerman et al,
Summary. Endotoxin (E. coli 0111; 2.5 mg/kg) was given via an aortic cannula to groups of normal and factor‐VII deficient dogs to determine whether factor‐VII deficiency afforded protection against endotoxin‐induced shock and intravascular coagulation. Normal dogs showed the dramatic fall in blood pressure characteristic of endotoxin shock and became deeply unconscious throughout the 5 hr period of the experiment. The factor‐VII deficient dogs had a niarkedly less dramatic response. The fall in blood pressure was significant but only transitory and the dogs required additional anaesthesia. Endotoxin‐induced intravascular coagulation occurred in both normal and factor‐VII deficient dogs. However, the decrease in factor‐V activity was greater, and the platelets returned to normal levels more slowly, in normal dogs than in factor‐VII deficient dogs. Plasminogen levels fell significantly in normal dogs, but not in the factor‐VII deficient animals. Autopsies revealed marked differences between the groups. Fibrin‐containing thrombi were regularly observed in normal dogs, but in factor‐VII deficient dogs such lesions were absent or minimal. Hereditary factor‐VII deficiency may therefore afford protection against endotoxin‐induced shock and intravascular coagulation. The difference in intravascular coagulation may explain the modified shock response in factor‐VII deficient dogs or vice versa, but convincing evidence for a causal relationship has not yet been collected.
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