The relationship between low survival and acute increase of tumor necrosis factor α expression in the lung in a rat model of asphyxial cardiac arrest / 대한해부학회지

Cardiac arrest (CA) is sudden loss of heart function and abrupt stop in effective blood flow to the body. The patients who initially achieve return of spontaneous circulation (RoSC) after CA have low survival rate. It has been known that multiorgan dysfunctions after RoSC are associated with high morbidity and mortality. Most previous studies have focused on the heart and brain in RoSC after CA. Therefore, the aim of this research was to perform serological, physiological, and histopathology study in the lung and to determine whether or how pulmonary dysfunction is associated with low survival rate after CA. Experimental animals were divided into sham-operated group (n=14 at each point in time), which was not subjected to CA operation, and CA-operated group (n=14 at each point in time), which was subjected to CA. The rats in each group were sacrificed at 6 hours, 12 hours, 24 hours, and 2 days, respectively, after RoSC. Then, pathological changes of the lungs were analyzed by hematoxylin and eosin staining, Western blot and immunohistochemistry for tumor necrosis factor α (TNF-α). The survival rate after CA was decreased with time past. We found that histopathological score and TNF-α immunoreactivity were significantly increased in the lung after CA. These results indicate that inflammation triggered by ischemia-reperfusion damage after CA leads to pulmonary injury/dysfunctions and contributes to low survival rate. In addition, the finding of increase in TNF-α via inflammation in the lung after CA would be able to utilize therapeutic or diagnostic measures in the future.

Changes in histopathology and tumor necrosis factor-α levels in the hearts of rats following asphyxial cardiac arrest

OBJECTIVE: Post cardiac arrest (CA) syndrome is associated with a low survival rate in patients who initially have return of spontaneous circulation (ROSC) after CA. The aim of this study was to examine the histopathology and inflammatory response in the heart during the post CA syndrome. METHODS: We induced asphyxial CA in male Sprague-Dawley rats and determined the survival rate of these rats during the post resuscitation phase. RESULTS: Survival of the rats decreased after CA: 66.7% at 6 hours, 36.7% at 1 day, and 6.7% at 2 days after ROSC following CA. The rats were sacrificed at 6 hours, 12 hours, 1 day, and 2 days after ROSC, and their heart tissues were examined. Histopathological scores increased at 12 hours post CA and afterwards, histopathological changes were not significant. In addition, levels of tumor necrosis factor-α immunoreactivity gradually increased after CA. CONCLUSION: The survival rate of rats 2 days post CA was very low, even though histopathological and inflammatory changes in the heart were not pronounced in the early stage following CA.

Neuroprotective Effect of N-acetylcysteine in an Asphyxial Cardiac Arrest Model of Rats

BACKGROUND: A major pathway leading toward neuronal injury following ischemia-reperfusion of the brain involves elevation of extracellular glutamate and activation of glutamate receptors, with a subsequent increase in intracellular calcium, resulting in a generation of free radicals. Oxygen free radicals cause brain injury following resuscitation from cardiac arrest. Oxyradicals produce strand breakage in DNA, which triggers energy-consuming DNA repair mechanisms and activates the nuclear enzyme poly(ADP-ribose) synthetase(PARS). However, excessive PARS activation leads to energy depletion and exacerbation of neuronal damage in cerebral ischemia. METHODS: We investigated the effect of a potent, free-radical scavenger, N-acetylcysteine(NAC), on hippocampal neuronal death in an asphyxial cardiac arrest model of rats. The effect of NAC on hippocampal neuronal death was studied in 32 rats which were subjected to asphyxial cardiac arrest for 7 minutes, followed by resuscitation. The animals were divided into four group(8 rats in each group) as follows: Group I was saline treated for 3 days, Group II was NAC treated for 3 days, Group III was saline treated for 6 days, and Group IV was NAC treated for 6 days. In the NAC-treated groups, NAC(150 mg/kg) was intravenously injected after return of spontaneous circulation. The coronal sections with hippocampus levels were stained with hematoxylin-eosin(H-E) and PARS antibodies at 3 and 6 days after survival. In addition, the levels of myeloperoxidase(MPO) and malondialdehyde(MDA) were determined in the brains of each group. RESULTS: The results are as follows: 1. MPO and MDA levels were significantly lower in the NAC-treated groups, II and IV, than in the saline-treated groups, I and III. 2. The histologic damage score(HDS), as determined by H-E staining, was significantly lower in the NAC-treated groups, II and IV, than in the saline-treated groups, I and III. 3. In PARS immunohistochemical staining, the HDS was significantly lower in the NAC-treated groups, II and IV, than in the saline-treated groups, I and III. CONCLUSION: These results suggest that a free-radical scavenger, N-acetylcysteine, may effectively prevent neuronal damages after reperfusion from asphyxial cardiac arrest in rats. Further studies will be required to examine both the mechanism of the action and the clinical application of NAC in patients with cardiac arrest.