Abstract Body: Introduction: The impact of global ischemia and reperfusion on the brain in resuscitation animal models is well investigated whereas the spinal cord and its protection are rarely reported. We investigated the spinal cord in our ventricular fibrillation cardiac arrest (VFCA) extracorporeal cardiopulmonary resuscitation (eCPR) rat model and hypothesized that an untreated VFCA of 8 minutes will lead to dysfunction and histological damage in the spinal cord and that treatment with hypothermic temperature (HT) control for 12 hours to 33°C will minimize these pathological findings.
Methods: Adult male Sprague-Dawley rats (n=16, 400-800 g) were subjected to 8 min of VFCA and resuscitated with eCPR and drugs (epinephrine, bicarbonate, heparin). After defibrillation and restoration of spontaneous circulation (ROSC), rats were randomized in normothermic (NT) (n=9) and HT group (n=7). After 24h of survival the neurologic damage score (NDS, 0-100%) was assessed and the spine was fixed in formalin. The spinal cord was removed after fixation and cervical, thoracic, and lumbar transverse sections were embedded in paraffin. Hematoxylin and Eosin (HE)-staining and immunohistochemistry with an antibody against Iba1 were performed. Sections were evaluated in a semiquantitative way (mild, moderate, marked lesions) and compared to sham animals (n=7) by a pathologist blinded to treatment regimens.
Results: All animals achieved ROSC, but two NT animals died before the study endpoint. NT animals showed consistent spastic paralysis of all extremities and urinary retention, while motoric function was improved in the HT group. Accordingly, the NDS in the HT group was significantly better compared to the NT group (HT Median 26 [IQR11] % / NT Median 40 [IQR16] % (p-value = 0.014)). In HE-staining, four of seven HT animals showed scattered to mild neuronal necrosis (NN) in the gray matter. In contrast, all animals of the NT group showed moderate to marked NN, which is a significant increase compared to both, the HT group and the sham group. In both VFCA groups activation of microglia was significantly increased compared to sham.
Conclusions: We found consistent NN in the spinal cord of rats kept under normothermic conditions for 24h after 8 min of untreated VFCA and eCPR. In the HT group these lesions were significantly reduced, which correlates with the neurological outcome. However, the microglial reaction after this short survival time did not differ between the VFCA groups.