Protection by desferrioxamine against histopathological changes of the liver in the post-oligaemic phase of clinical haemorrhagic shock in dogs: correlation with improved survival rate and recovery.
Haemorrhagic shock was produced in anaesthetized dogs, by rapid arterial bleeding to mean arterial blood pressure 35 mmHg, and maintained oligaemic for 4 h followed by return of withdrawn blood(ROWB). Dogs were observed for 72 h after ROWB for survival and recovery, and, for histopathological (HP) studies on liver, dogs were sacrificed 2 h after ROWB in non-survival experiments. Desferrioxamine mesylate (25 mg/kg) was administered intra-muscularly at 2,3 and 4 h after blood loss in survival experiments and for HP studies the drug was given at 4 h in one group and at 2 h plus 4 h after blood loss in the second group. With the drug given at 3 or 4 h, survival was 70% and 100% while in the 2 h and the untreated groups it was 50%. Recovery was rapid in all the drug treated survivors, few became conscious within 30 min, showed slight activity by 4-6 h, all were almost normally active by 24 and fully so by 72 h after ROWB. All the 5 control survivors remained unconscious/drowsy upto 24 h; 3 were sluggish at 72 h. By group analysis, serum iron elevation during the oligaemic and at the end of the post-oligaemic phase was less in the drug-treated animals. HP changes of shock in the liver studied by light microscopy, were markedly reduced in severity and were less prevalent in the drug-treated dogs. The salutory effects of desferrioxamine may be due to inhibition of iron catalyzed free-radical production and tissue damage, through its strong iron chelating action. It may have a therapeutic advantage in this emergency condition without the disadvantages of toxicity inherent in prolonged use.
Sanan
S
S
Department of Pharmacology, Medical College, Amritsar, Punjab, India.
Sharma
G
G
Malhotra
R
R
Sanan
D P
DP
Jain
P
P
Vadhera
P
P
D000818:Animals; D003676:Deferoxamine / Q000494:pharmacology / Q000627:therapeutic use*; D004285:Dogs; D005260:Female; D008099:Liver / Q000187:drug effects / Q000473:pathology*; D008297:Male; D012016:Reference Values; D012771:Shock, Hemorrhagic / Q000473:pathology* / Q000517:prevention & control
D003676:Deferoxamine