Mild therapeutic hypothermia decreases oxidative damage and increases glutathione levels in post-cardiac arrest patients

Background The post-cardiac resuscitation syndrome is a pathophysiologic state after the successful cardiopulmonary resuscitation in cardiac arrest patients. Ischemia-reperfusion-induced oxidative stress is one of the main mechanisms of tissue injury after cardiac arrest [1]. A decrease in antioxidant defenses may contribute to ischemia-reperfusion injury [2]. The mild hypothermia treatment may improve the tissue damage in post-cardiac arrest patients [3]. Mild therapeutic hypothermia is known to decrease the levels of oxidative damage biomarkers, as previously shown by our research group [4]. The mechanisms involving cardiac arrest pathophysiology and hypothermia treatment are not well elucidated. Methods Intensive care unit patients admitted in 2011 and 2012, victims of in-hospital or out-of-hospital cardiac arrest were screened for the study. The sample consisted of 31 patients under controlled normothermia (36oC) and 11 patients treated with mild therapeutic hypothermia (33oC). Mild hypothermia was induced 4-5h after successful cardiopulmonary resuscitation for 24 h. Clinical data and venous blood samples were collected 6, 12, 36 and 72 h post-cardiac arrest. We investigated lipid (malondialdehyde levels) and protein (carbonyl levels) damage biomarkers, and also investigated the levels of the antioxidants glutathione, vitamin C and vitamin E, and nitric oxide levels at 6, 12, 36, and 72 h after cardiac arrest. Data were compared by multivariable logistic-regression models with generalized estimating equations and pairwise comparisons of estimated means by the post-hoc Bonferroni method. Results Serum malondialdehyde and plasma carbonyl levels were decreased in hypothermic group at 6, 12, 36, and 72 h after cardiac arrest in hypothermic patients [4]. Also, erythrocyte glutathione levels were elevated by mild therapeutic hypothermia at all time-points, while serum Vitamin C levels decreased significantly at 6 and 12 h after cardiac arrest in hypothermic patients, coinciding with the period of therapeutic hypothermia. Serum vitamin E and erythrocyte nitric oxide levels were not altered by hypothermic treatment. Discussion The present results evidence that hypothermia can reduce oxidative damage in post-cardiac arrest patients. Moreover, our findings reported, for the first time, increased glutathione levels after cardiac arrest in hypothermic patients as compared to all time points in normothermic patients. There is no previous evidence or possible mechanism corroborating a decrease in vitamin C levels as a consequence of hypothermia. Conclusions These findings suggest that mild therapeutic hypothermia may reduce oxidative damage to lipids and proteins, and concomitantly elevate glutathione levels. Therefore, mild therapeutic hypothermia may contribute to the tissues protection from ischemia-reperfusion injury after cardiac arrest by decreasing oxidative stress.