A comprehensive study of survival, tissue damage, and neurological dysfunction in a murine model of cardiopulmonary resuscitation after potassium-induced cardiac arrest.

There are only few strategic and therapeutic options to improve the functional outcome of patients after cardiac arrest and resuscitation (CPR). The pathophysiology of reperfusion injury after global ischemia is not completely understood. We present here a murine model of cardiac arrest and resuscitation that allows an analysis of the pathophysiology of reperfusion injury, especially focusing on survival, tissue damage, and functional neurological parameters. Under systemic hemodynamic monitoring, male C57BL/6J mice were subjected to 3 min of a potassium-induced cardiac arrest. After resuscitation under controlled conditions, mice were observed and neurologically scored for 72 h post-CPR. As a control, sham-treated animals were provided. In addition, blood samples were drawn and organs were removed for a histological analysis. Here, global I/R led to functional and histological reperfusion damage. The overall mortality up to day 3 post-CPR was 54%. Resuscitated animals developed marked functional neurologic deficits, as assessed by Rotarod and elevated plus-maze testing. Histological examinations and blood analyses of CPR animals revealed significant leukocyte tissue infiltration and morphological damage of brain, lung, and kidneys. In summary, mice undergoing CPR after cardiac arrest present distinct neurological deficits, marked organ damage, and a 54% mortality rate. Our highly standardized and reproducible model of mice resuscitation provides a means for a better understanding of the post-CPR pathophysiology and thus opens new perspectives to develop relevant therapeutic approaches to minimize global I/R injury.