I. Aroch1; G. Segev1; Y. Avital1; I. Ginsburg2; A. Merisat3; M. Horowitz3; Y. Bruchim1
Canine heatstroke is a systemic inflammatory response syndrome (SIRS), often leading to multiple organ dysfunction, encephalopathy, and death. Currently, there is no specific treatment to decrease the hyperthermia-induced inflammatory, and haemostatic derangements. Histones are highly conserved, positively-charged nuclear proteins, serving as the chromatin basic structure block unit. They leak from damaged cells, exhibiting toxic, pro-inflammatory, pro-thrombotic properties. Histones can be targeted pharmacologically, thereby offering a potential therapeutic target in SIRS. Serum histone concentration (sHs) was measured in 16 dogs with naturally-occurring heatstroke at presentation and in 7 healthy controls using a commercially available ELISA. Median sHs was significantly (p=0.043) higher in the heatstroke group vs. the control group (13.2 vs. 7.3 ng/mL, respectively), in those with severe haemostatic derangement vs. the other dogs (median 19.0 L, range 4.6–40 vs. median 7.0, range 4.6–34.6 ng/mL, respectively; p=0.038), and in non-survivors vs. survivors of heatstroke (21.4, range 4.2–40.0 vs. median 8.16, range 2.8–19.0 ng/mL, respectively; p=0.049). sHs was significantly correlated with serum urea (r=0.8) and total CO2 (r=0.7) concentrations and creatine kinase activity (r=0.7) at presentation, and with prothrombin time at 12 hours post-presentation (r=0.9). The area under the ROC curve of sHs concentration as a predictor of death was 0.72, (cutoff point, 13.7 ng/mL; sensitivity, 60%; specificity 88%). sHs are measurable in dogs by ELISA. The correlations between sHs and other biomarkers of disease severity, and its increase in severely affected dogs (i.e., the non-survivors), suggest a role of sHs in the inflammation and haemostatic derangement in canine heatstroke.
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