Abstract

Purpose To investigate the neuroprotective effects of methylene blue (MB) in a clinically relevant porcine model of cardiac arrest. Method: 40 anaesthetized pigs were subjected to myocardial infarction and seven minutes of untreated cardiac arrest. Animals were randomized into three groups: one group received saline only (control), one group received 2 mg/kg MB and saline (MB+saline), and one group received two doses of 2 mg/kg MB (MB+MB). The first intervention was given after the 3rd rhythm analysis, while the second dose was administered one hour after achieving return of spontaneous circulation (ROSC). The main investigator was blinded during resuscitation and the first hour after ROSC. Animals underwent intensive care and observation for 6 hours. Neurological outcomes were evaluated by cerebral microdialysis and serum-neuron specific enolase (NSE). Normality was assessed by qq-plot and histograms. Pointwise data were analyzed using Kruskal-Wallis test as data did not assume normal distribution. Data are presented as medians and 25 th and 75 th percentiles. A value of p<0.05 was considered statistically significant. Results: The proportion of animals achieving ROSC was similar across groups: 11/13 (85%) in the control group, 10/13 (77%) in the MB+saline group, and 12/14 (86%) in the MB+MB group (p=0.81). Cerebral lactate and pyruvate levels increased after ROSC in all groups. Lactate/pyruvate ratios were comparable between groups two hours after ROSC (control: 25 (22;31); MB+saline: 24 (22;36); MB+MB: 23 (20;28); p=0.43). Cerebral glycerol levels initially increased in all groups with the highest levels at two hours after ROSC (control: 454 μmol/L (319;507); MB+saline 351 μmol/L (241;420); MB+MB 347 μmol/L (256;478); p=0.35). Glycerol levels decreased over time with no difference 6 hours after ROSC (control: 210 μmol/L (138;293); MB+saline (146 μmol/L (61;156); MB+MB: 105 μmol/L (63;159); p=0.07). Serum-NSE levels 6 hours after ROSC were not different between groups (control: 0.9 μg/L (0.7;1.5); MB+saline 1.5 μg/L (1.0;2.0); MB+MB: 1.0 μg/L (0.7;1.2); p=0.13). Conclusion Contrary to previous publications the current porcine trial did not observe any neuroprotective effects of MB when evaluated by cerebral microdialysis and NSE levels.

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