Modeling Hemorrhagic Shock in Male SD Rats by Fixed Volume Blood Withdrawal Followed by Partial Resuscitation and...

Background/Objectives: Hemorrhagic shock (HS) is one of the leading causes of disability and mortality in intensive care units. Animal modeling of HS is important for preclinical research to elucidate mechanisms and develop treatments. Methods: Adult male SD rats were divided into three groups, half of which were euthanized on day 8 and the other half on day 29 after HS. HS was simulated in awake animals by withdrawing blood from the carotid artery at a volume of 40% of circulating blood volume (CBV). One hour after HS, volume resuscitation therapy (VRT) was made by administering albumin-containing saline (AS) or autologous blood (AB) at 20% of CBV. Arterial pressure (AP), heart rate (HR), body temperature, blood gases, and blood metabolites, body weight gain, hemostasis, and blood cellular composition were analyzed. On days 8 and 29, bone marrow composition, organ weight, and histology were analyzed. Results: During blood withdrawal, AP dropped, HR increased, and hypothermia developed. After HS and subsequent VRT, 30% of animals receiving SA died, while all animals receiving AB survived. Following HS, a negative weight gain trend, anemia, pronounced inflammatory reaction, and coagulopathy developed. After HS, animals experienced an increase in partial oxygen pressure, a decrease in partial carbon dioxide pressure, total arterial oxygen content in arterial blood, stress-induced glycemia, and metabolic lactatemia. In bone marrow, the number of erythroid cells increased, while leukocyte and lymphocyte numbers decreased. HS resulted in increased spleen weight with increased extramedullary hematopoiesis. Ischemic kidney tissue damage with a decrease in kidney weight was observed, as well as post-ischemic accidental thymus involution with a catastrophic decrease in its weight. In addition, ischemic brain damage was observed in some animals. Animals showed a compensatory increase in hematopoiesis. All changes were less pronounced in AB-treated animals. Conclusions: We have developed a suitable model of HS, comparable to a similar condition in humans. This model can be easily reproduced and applied in most laboratories conducting preclinical studies.