A Novel Pre-Clinical Modeling of Massive Hemorrhagic Shock in Non-Human Primate: A Safe and Reproducible Method (Macaca fascicularis)

Abstract

Background: Although non-human primates are the closest animals to humans to simulate physiological and metabolic responses, there is a paucity of primate hemorrhagic shock models that are standardized and reproducible. Herein, we describe a model that is a clinical replica of extreme class IV hemorrhagic shock with a step-by-step description of the procedure in cynomolgus macaque monkeys. Methods: The physiological changes that occurred during the process were evaluated using hemodynamic parameters, echocardiogram, and laboratory values. Five female monkeys were subjected to trauma laparotomy, followed by cannulation of the abdominal aorta to achieve graded hemorrhage. A central line was placed in the right internal jugular vein, which was subsequently used for laboratory sampling and volume resuscitation. The withdrawal of blood was ceased when a predefined cardiac endpoint with cardiac arrhythmia or bradycardia was reached. The animals were then immediately resuscitated with transfusion. The primary cardiac endpoint was consistently reached in all 5 animals during the fourth hemorrhage when more than 70% of the estimated total blood volume was lost. Results: No mortality occurred during the process. The blood pressure, cardiac output measured from an echocardiogram, and hemoglobin correlated well with increasing loss of circulating volume, whereas the pulse pressure variation did not. The echocardiogram was also a useful predictor for urgent volume replacement. Conclusion: This model offers a safe and reproducible surgical hemorrhagic model in non-human primates and simulates clinical practice. This could provide a useful platform on which further studies can be carried out to address unanswered questions in trauma management. © 2024 Elsevier Inc.