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Updated: May 2, 2026
Author Spotlight: Developing Innovative Therapeutic Strategies for Hemorrhagic Shock Research
Published on: March 22, 2024
Blood pressure-targeted stepwise resuscitation for hemorrhagic shock in rats
Jae Hyuk Lee1, Kyuseok Kim, You Hwan Jo
1From the Department of Emergency Medicine (J.H.L., K.K., Y.H.J., J.E.R., A.R.D., M.J.L., C.J.P., J.K., H.C.), Seoul National University Bundang Hospital, Seongnam-si, Gyeonggi-do; and Department of Pathology (M.A.K, K.B.L.), Seoul National University Hospital, Seoul, Korea.
Background:
Generation of reactive oxygen species (ROS) is an important mechanism of ischemia-reperfusion injury. Abrupt reoxygenation compared with slow reoxygenation has been known to increase ROS generation. Thus, slow and stepwise reperfusion can reduce ROS generation and subsequent ischemia-reperfusion injury. This study investigated the effect of slow reperfusion by blood pressure-targeted stepwise resuscitation (PSR) in hemorrhagic shock.
Methods:
Pressure-controlled hemorrhagic shock was induced in male Sprague-Dawley rats for 1 hour. Rats were then allocated to one of three groups (no-resuscitation group, n = 14; PSR group, n = 15; rapid normalization of blood pressure (RR) group, n = 15). Survival time and hemodynamic changes were recorded and compared. Blood samples and liver tissue were harvested after 6 hours of resuscitation in surviving rats.
Results:
All of the rats in the no-resuscitation group were expired before the end of the 6-hour observation period. Survival times were significantly longer in the PSR group than in the RR group (survival rates, 11 of 15 vs. 5 of 15, log rank p = 0.032). Plasma amino alanine transferase, histologic liver injury, and ROS generation in the liver tissue were significantly lower in the PSR group than in the RR group (all findings significant, p < 0.05). In addition, PSR significantly decreased plasma nitric oxide, liver interleukin 1β, and liver interleukin 6 compared with rapid resuscitation in addition to augmenting Akt survival pathways (all p < 0.05).
Conclusion:
Slow reperfusion by PSR decreased mortality, ROS generation, and liver injury in rats undergoing hemorrhagic shock. Stepwise resuscitation also decreased inflammatory cytokine production and augmented Akt survival pathways.
