A new model of severe hemorrhagic shock in rats.

We here introduce a fixed-pressure model of hemorrhagic shock in rats that maximizes effects on mean arterial blood pressure (MAP) during shock and yet maintains high reproducibility and controllability. The MAP of rats was adjusted to 25 to 30 mm Hg by blood withdrawals during 30 min. After a shock period of 60 min, rats were resuscitated either with lactated Ringer solution (LR) only or with the collected blood 3-fold diluted with LR (LR + blood) and monitored for further 150 min. Throughout the experiment, vital parameters and plasma marker enzyme activities and creatinine concentration were assessed. Thereafter, liver, kidneys, small intestine, heart, and lung were harvested and evaluated histopathologically. Vital parameters, plasma marker enzyme activities, creatinine concentration, and histopathology indicated pronounced but reliable and reproducible systemic effects and marked organ damage due to hemorrhagic shock and resuscitation. In contrast to rats that received LR + blood, which survived the postresuscitation period, rats receiving LR only invariably died shortly after resuscitation. The hemorrhagic shock model we present here maximally affects MAP and yet is highly reproducible in rats, allowing the study of various aspects of hemorrhagic shock and resuscitation under clinically relevant conditions.