A lethal syndrome in mice following administration of carbon tetrachloride and cycloheximide, and its prevention by heparin treatment.

When a hepatotoxic dose of CCl4 is followed in 6 h (but not in 18 h) by 30 micrograms per g body weight of cycloheximide, a lethal, shock-like state develops. This is prevented by heparin treatment. This lethal syndrome is compared with other, similar, induced lethal states in which cycloheximide plays an essential role, and in which heparin is lifesaving. It is postulated that, after CCl4, a phase of procoagulant activity occurs in the dying centrilobular zone hepatocytes, but that unimpaired protein synthesis permits responsive release of endogenous heparin and thereby prevents thrombosis in centrilobular sinusoids. Cycloheximide is thought to inhibit this heparin release and to allow a transient episode of occlusive centrilobular microthrombosis with consequent irreversible ischaemic damage to the mid-gut.