Evaluation of novel vanilloid-based hemostatic agents in rats.
BACKGROUND
: Hemostatic dressings containing clotting factors, biodegradable matrices, and recombinant proteins have been developed to control bleeding for battlefield trauma and trauma in clinical settings. Our present study evaluates the use of a vanilloid compound in biodegradable hemostatic dressings in a rat model of trauma.


METHODS
: Male Sprague-Dawley rats (n = 180) were randomly divided into treatment groups and control groups and subjected to a lethal groin injury at 30 degrees C and 37 degrees C. Treatment groups included hemostatic matrices consisting of Protosan and graded doses of 2.5%, 5%, 10%, 15%, and 20% of the vanilloid agonist CAP-305. Powder or bilayer patch formulations were applied to the injury site. The seal integrity was assessed by reperfusion of the animal to a minimum mean-arterial pressure (MAP) of 80 mm Hg and monitoring for 60 minutes postinjury.


RESULTS
: Powder and patch formulations loaded with varying concentrations of CAP-305 were evaluated. Powders containing 2.5% to 20% drug by weight showed 40% to 80% seal rates at 37 degrees C (p < 0.0001), whereas no significant results were obtained at 30 degrees C compared with the control animals. Conversely, bilayer patches loaded with 5% to 20% drug exhibited a consistent 70% seal rate (p < 0.0001) at 37 degrees C and 70% to 90% seal rates (p < 0.0001) in hypothermic animals when compared with controls.


CONCLUSIONS
: Our study demonstrates the efficacy of CAP-305 loaded hemostatic dressings in the rat model of lethal groin injury. This study provides relevant proof of concept for the development of vanilloid agonists as hemostatic agents.
Bhattacharjee
Himanshu
H
From the Department of Pharmaceutical Sciences, University of Tennessee Health Science Center, Memphis, Tennessee.
Gurley
Steven N
SN
Allison
Patrick B
PB
Zhang
Xiofeng
X
Moore
Bob M
BM
D000287:Administration, Topical; D000818:Animals; D001458:Bandages; D048271:Chitosan; D003094:Collagen; D004195:Disease Models, Animal; D005263:Femoral Artery / Q000293:injuries*; D006490:Hemostatics / Q000008:administration & dosage*; D008297:Male; D011208:Powders; D051381:Rats; D017207:Rats, Sprague-Dawley; D012771:Shock, Hemorrhagic / Q000209:etiology / Q000517:prevention & control*; D050916:TRPV Cation Channels / Q000008:administration & dosage* / Q000819:agonists*; D014950:Wounds, Penetrating / Q000150:complications / Q000628:therapy*
D006490:Hemostatics; D011208:Powders; D050916:TRPV Cation Channels; D003094:Collagen; D048271:Chitosan