Evaluation of desferrioxamine mesylate on survival, and prevention of histopathological changes in the liver, in haemorrhagic shock: an experimental study in dogs.
Desferrioxamine mesylate (desferal) an iron chelating agent was investigated in anaesthetized standard haemorrhagic shock (HS) dogs with elective hypotension at 35 +/- 5 mmHg for 4 h and return of withdrawn blood (ROWB) thereafter. Observations were made in respect of serum iron elevation over 4 h and survival and recovery pattern over 72 h after ROWB. Influence of the drug on histopathological changes of shock in liver were studied in non-survival experiments (dogs sacrificed after 4 h of elective hypotension). Desferal administration (25 mg/kg i.m.) at 30 min after initial bleeding, increased the 72 h survival from 10% (controls) to 50%, and reduced the serum iron elevation from 63.3% (controls) to 9.44%. The single control survivor remained unconscious till 24 h and sluggish in activity up to 72 h. Three of the drug treated survivors regained consciousness by 2 h, activity by 24 h and all were normally active by 72 h. Severe congestive and degenerative changes in liver, present in the controls, were markedly reduced in severity and incidence in those given desferal. It is suggested that iron decompartmentalization in the hypoxic tissues in HS with its consequent rise in serum and intracellular pool, plays a pivotal role in progression towards irreversibility. Desferal, an effective intracellular iron chelator, possibly arrests the widespread cellular damage caused through enhanced iron-catalysed .OH radical generation in shock state.
Sanan
S
S
Department of Pharmacology, Medical College, Amritsar, Punjab, India.
Sharma
G
G
Singh
B
B
Sanan
D P
DP
Wadhera
P
P
D000818:Animals; D002614:Chelating Agents / Q000627:therapeutic use*; D003676:Deferoxamine / Q000627:therapeutic use*; D004285:Dogs; D005260:Female; D008099:Liver / Q000187:drug effects*; D008297:Male; D012771:Shock, Hemorrhagic / Q000188:drug therapy* / Q000401:mortality; D013997:Time Factors
D002614:Chelating Agents; D003676:Deferoxamine