Rat Strains Bred for Low and High Aerobic Running Capacity Do Not Differ in Their Survival Time to Hemorrhage

Abstract

Hemorrhagic shock reflects low tissue perfusion that is inadequate to maintain normal metabolic functions. Often associated with this condition are impairments in cellular oxygen delivery and utilization. Rat strains divergent in their running endurance have been artificially selected over 12 generations. As these rats bred for high (HCR) vs low (LCR) aerobic running capacity have greater tissue O2 utilization capacity and improved cardiovascular function, we hypothesized that HCR would be more tolerant (i.e., have greater survivability) to the global ischemia of hemorrhagic shock than LCR. To address this hypothesis, survival time to a severe --as substantiated by dramatic changes in plasma lactate, HCO3, and base deficit--controlled hemorrhage was measured. Male rats were catheterized and, ∼ 24 hours later, an estimated > 35% of the calculated blood volume was removed during a 26 min period while the rats were conscious and unrestrained. Rats were observed for 6 hr or until death. Contrary to our hypothesis, survival time in HCR (220 ± 63 min; n=6) did not differ statistically (P = 0.46) from that in LCR (279 ± 53 min; n=7). Similarly, there were no statistical differences (P ≥ 0.08) between rat lines in blood pH, lactate, HCO3, and base deficit pre or post-hemorrhage. In addition, few significant differences between lines in response to hemorrhage were detected by measures of cellular antioxidant status in heart, liver or lung. Since animals with genetically greater tissue oxygen utilization capacity failed to show longer survival times, our results suggest that other mechanisms must play a more dominant role in determining survivability to hemorrhage under conditions of this hemorrhage.

Influence of Intrinsic Aerobic Exercise Capacity and Sex on Cardiac Injury Following Acute Myocardial Ischemia and Reperfusion

“…The HCR phenotype has been associated with increased longevity generally (32), which means it might also be possible that there is less benefit from the phenotype in an acute injury model such as the one used in this study, than in a more chronic, progressive disease setting such as high fat feeding (18,33). It is also possible that the effect seen here is tissue dependent, but others have reported no difference between phenotypes in survival from multisystem stress in a model of hemorrhagic shock (34). We also did not complete any longer-term outcomes following the ischemia reperfusion injury.…”

Life or Death? A Physiogenomic Approach to Understand Individual Variation in Responses to Hemorrhagic Shock

“…The vertical dashed line represents 360 min, the maximum observation period at which rats were euthanized if still alive (censored data). Rat strains: Brown Norway Medical College of Wisconsin (BN/Mcwi), Dahl Salt-Sensitive (S), Brown Norway (BN), Outbred Sprague Dawley (Outbred), Copenhagen 2331 (COP), Dahl Salt-Resistant (R), Lewis (Lew), Munich Wistar Fromter (MWF), BDIX, Spontaneously Hypertensive (SHR), Noble, Fawn Hooded Hypertensive (FHH), Black agouti (ACI), PVG, FISCHER 344 (F344), and Dark Agouti (DA) [ 33 ]. Reproduced with permission from Lippincott, Williams, & Wilkins.…”