title: Genetic influences on survival time after severe hemorrhage in inbred rat strains.
abstract: To find a genetic basis for differential ability to survive severe hemorrhage, we previously showed eightfold differences in survival times among inbred rat strains. We assumed that rat strains had similar normalized blood volumes (NBV; ml/100 g body wt). As NBV might vary among strains and constitute one genetic variable affecting survival time to hemorrhage, in experiment 1 of the current studies we first measured total blood volumes and calculated NBV in specific inbred rat strains (Brown Norway/Medical College of Wisconsin, BN; Dark Agouti, DA; Fawn Hooded Hypertensive, FHH; Lewis, LEW; and Dahl Salt-Sensitive, SS) previously found to be divergent in survival time. NBV differed by 20% (P < 0.01; BN > SS > FHH = LEW = DA) and had a heritability (h(2)) of 0.56. Hence, differential survival times in our previously published study might reflect strain-dependent differences in NBV. Then studies were conducted wherein rats were catheterized and, ∼24 h later, 47% of their blood volume was removed; these rats were observed for a maximum of 4 h. In experiment 2, blood volumes were measured the day prior to hemorrhage. Percent survival and survival time did not differ among strains. To obviate possible confounding effects of blood volume determination, in experiment 3 the average NBV for each strain was used to determine hemorrhage volumes. Percent survival (P < 0.01) and survival times (P < 0.001) were different with DA demonstrating the best (62.5%, 190 ± 29 min) and BN the worst (0%, 52 ± 5 min) survival responses. These data indicate that both blood volume and survival time after hemorrhage in rats are heritable quantitative traits, and continue to suggest that genetic assessment of these phenotypes might lead to novel therapeutics to improve survival to hemorrhage.
authors.affiliation: U.S. Army Institute of Surgical Research, Fort Sam Houston, Texas. harold.klemcke@amedd.army.mil
authors.forename: Harold G
authors.initials: HG
authors.lastname: Klemcke
authors.forename: Bina
authors.initials: B
authors.lastname: Joe
authors.forename: Mariam L
authors.initials: ML
authors.lastname: Calderon
authors.forename: Rajiv
authors.initials: R
authors.lastname: Rose
authors.forename: Thomas
authors.initials: T
authors.lastname: Oh
authors.forename: James
authors.initials: J
authors.lastname: Aden
authors.forename: Kathy L
authors.initials: KL
authors.lastname: Ryan
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001810:Blood Volume / Q000235:genetics / Q000502:physiology*; D006470:Hemorrhage / Q000235:genetics / Q000401:mortality* / Q000503:physiopathology*; D019655:Quantitative Trait, Heritable; D051381:Rats; D011919:Rats, Inbred Strains / Q000235:genetics*; D013045:Species Specificity; D015996:Survival Rate