Insights into pathophysiology and therapeutic strategies for heat stroke: Lessons from a baboon model

Heat stroke is a perilous condition marked by severe hyperthermia and extensive multiorgan dysfunction, posing a considerable risk of mortality if not promptly identified and treated. Furthermore, the complex biological mechanisms underlying heat stroke-induced tissue and cell damage across organ systems remain incompletely understood. This knowledge gap has hindered the advancement of effective preventive and therapeutic strategies against this condition. In this narrative review, we synthesize key insights gained over a decade using a translational baboon model of heat stroke. By replicating heat stroke pathology in a non-human primate species that closely resembles humans, we have unveiled novel insights into the pathways of organ injury and cell death elicited by this condition. Here, we contextualize and integrate the lessons learned concerning heat stroke pathophysiology and recovery, areas that are inherently challenging to investigate directly in human subjects. We suggest novel research directions to advance the understanding of the complex mechanisms underlying cell death and organ injury. This may lead to precise therapeutic strategies that benefit individuals suffering from this debilitating condition. What is the topic of this review?The review focuses on understanding the pathophysiology of heat stroke using a translational baboon model.What advances does it highlight?The baboon model has unveiled intricate mechanisms of inflammatory, coagulation and cell death processes during heat stroke, and tested therapeutic interventions. Treatments targeting individual pathways were found ineffective, highlighting the complexity of heat stroke pathophysiology.