title: Crotalus atrox venom preconditioning increases plasma fibrinogen and reduces perioperative hemorrhage in a rat model of surgical brain injury.
abstract: Perioperative bleeding is a potentially devastating complication in neurosurgical patients, and plasma fibrinogen concentration has been identified as a potential modifiable risk factor for perioperative bleeding. The aim of this study was to evaluate preconditioning with Crotalus atrox venom (Cv-PC) as potential preventive therapy for reducing perioperative hemorrhage in the rodent model of surgical brain injury (SBI). C. atrox venom contains snake venom metalloproteinases that cleave fibrinogen into fibrin split products without inducing clotting. Separately, fibrinogen split products induce fibrinogen production, thereby elevating plasma fibrinogen levels. Thus, the hypothesis was that preconditioning with C. atrox venom will produce fibrinogen spilt products, thereby upregulating fibrinogen levels, ultimately improving perioperative hemostasis during SBI. We observed that Cv-PC SBI animals had significantly reduced intraoperative hemorrhage and postoperative hematoma volumes compared to those of vehicle preconditioned SBI animals. Cv-PC animals were also found to have higher levels of plasma fibrinogen at the time of surgery, with unchanged prothrombin time. Cv-PC studies with fractions of C. atrox venom suggest that snake venom metalloproteinases are largely responsible for the improved hemostasis by Cv-PC. Our findings indicate that Cv-PC increases plasma fibrinogen levels and may provide a promising therapy for reducing perioperative hemorrhage in elective surgeries.
authors.affiliation: Department of Physiology &Pharmacology, Loma Linda University School of Medicine, 11175 Campus St, Loma Linda, CA 92350, USA.
authors.forename: Cherine H
authors.initials: CH
authors.lastname: Kim
authors.affiliation: Department of Physiology &Pharmacology, Loma Linda University School of Medicine, 11175 Campus St, Loma Linda, CA 92350, USA.
authors.forename: Devin W
authors.initials: DW
authors.lastname: McBride
authors.affiliation: Department of Anesthesiology, Loma Linda University School of Medicine, 11175 Campus St, Loma Linda, CA 92350, USA.
authors.forename: Ronak
authors.initials: R
authors.lastname: Raval
authors.affiliation: Department of Physiology &Pharmacology, Loma Linda University School of Medicine, 11175 Campus St, Loma Linda, CA 92350, USA.
authors.forename: Prativa
authors.initials: P
authors.lastname: Sherchan
authors.affiliation: Department of Anesthesiology, Loma Linda University School of Medicine, 11175 Campus St, Loma Linda, CA 92350, USA.
authors.forename: Karen L
authors.initials: KL
authors.lastname: Hay
authors.affiliation: Department of Earth and Biological Sciences, Loma Linda University School of Medicine, 11175 Campus St, Loma Linda, CA 92350, USA.
authors.forename: Eric C K
authors.initials: EC
authors.lastname: Gren
authors.affiliation: Department of Earth and Biological Sciences, Loma Linda University School of Medicine, 11175 Campus St, Loma Linda, CA 92350, USA.
authors.forename: Wayne
authors.initials: W
authors.lastname: Kelln
authors.affiliation: Department of Physiology &Pharmacology, Loma Linda University School of Medicine, 11175 Campus St, Loma Linda, CA 92350, USA.|Department of Neurology, Loma Linda University School of Medicine, 11175 Campus St, Loma Linda, CA 92350, USA.
authors.forename: Tim
authors.initials: T
authors.lastname: Lekic
authors.affiliation: Department of Earth and Biological Sciences, Loma Linda University School of Medicine, 11175 Campus St, Loma Linda, CA 92350, USA.
authors.forename: William K
authors.initials: WK
authors.lastname: Hayes
authors.affiliation: Department of Pathology and Human Anatomy, Loma Linda University School of Medicine, Loma Linda, California, USA.
authors.forename: Brian S
authors.initials: BS
authors.lastname: Bull
authors.affiliation: Department of Anesthesiology, Loma Linda University School of Medicine, 11175 Campus St, Loma Linda, CA 92350, USA.
authors.forename: Richard
authors.initials: R
authors.lastname: Applegate
authors.affiliation: Department of Physiology &Pharmacology, Loma Linda University School of Medicine, 11175 Campus St, Loma Linda, CA 92350, USA.
authors.forename: Jiping
authors.initials: J
authors.lastname: Tang
authors.affiliation: Department of Physiology &Pharmacology, Loma Linda University School of Medicine, 11175 Campus St, Loma Linda, CA 92350, USA.|Department of Anesthesiology, Loma Linda University School of Medicine, 11175 Campus St, Loma Linda, CA 92350, USA.|Department of Neurosurgery Loma Linda University School of Medicine, 11175 Campus St, Loma Linda, CA 92350, USA.
authors.forename: John H
authors.initials: JH
authors.lastname: Zhang
mesh_terms: D000818:Animals; D001930:Brain Injuries / Q000378:metabolism / Q000473:pathology*; D017839:Crotalus / Q000378:metabolism; D004195:Disease Models, Animal; D005337:Fibrin / Q000378:metabolism; D005338:Fibrin Fibrinogen Degradation Products / Q000378:metabolism; D005340:Fibrinogen / Q000032:analysis*; D006406:Hematoma / Q000517:prevention & control; D006470:Hemorrhage / Q000517:prevention & control*; D019934:International Normalized Ratio; D007431:Intraoperative Complications; D008297:Male; D011517:Prothrombin Time; D051381:Rats; D017207:Rats, Sprague-Dawley; D012910:Snake Venoms / Q000627:therapeutic use*
chemical_list: D005338:Fibrin Fibrinogen Degradation Products; D012910:Snake Venoms; C036309:fibrin fragment D; D005337:Fibrin; D005340:Fibrinogen