Trans-sodium crocetinate and hemorrhagic shock.
Trans-sodium crocetinate (TSC) has been found to alleviate the symptoms of hemorrhagic shock in that, after the drug is given to hemorrhaged rats, blood pressure rises, elevated lactate levels are reduced, cellular damage in the liver and kidney is less, and survival is increased. The mechanism of action proposed for TSC is that it increases the diffusion of oxygen through blood plasma and into the tissue. The study reported here explores another proposed mechanism, the scavenging of free radicals. It is shown that TSC does scavenge radicals and may be more efficient than other free-radical scavengers. However, this may not be the mechanism of action for TSC during hemorrhagic shock. Not only are the TSC concentrations needed for radical scavenging greater than those which provide beneficial effects in hemorrhagic shock, but it is also shown that another radical scavenger, trolox, has no effect on oxygen consumption during shock. Trans-sodium crocetinate clearly holds promise as a useful treatment of hemorrhagic shock. Pharmacokinetics data are presented for different modes of administration. Initial studies suggest that instillation of TSC into the trachea or intramuscular injection may provide useful alternative treatment routes.
Stennett
Amanda K
AK
Fresenius Medical Care, Lexington, Massachusetts, USA.
Murray
Robert J
RJ
Roy
James W
JW
Gainer
John L
JL
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002338:Carotenoids; D016166:Free Radical Scavengers / Q000627:therapeutic use*; D007269:Injections, Intra-Arterial; D007273:Injections, Intramuscular; D008168:Lung / Q000187:drug effects; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012771:Shock, Hemorrhagic / Q000188:drug therapy*; D014801:Vitamin A / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use
D016166:Free Radical Scavengers; C487773:trans-sodium crocetinate; D014801:Vitamin A; D002338:Carotenoids