Moderate hypothermia suppressed excessive generation of superoxide anion radical and inflammatory reactions in blood and liver in heatstroke: Laboratory study in rats

Abstract

The study was performed to demonstrate superoxide radical (O(2).-) generation, systemic inflammation and liver injury caused by heatstroke and to reveal suppressive effects of moderate hypothermia. Heatstroke was defined as achieving pharyngeal temperature of 40 degrees C with arterial pressure reduction. Heatstroke rats were divided to four groups by the temperature after the onset; 40 degrees C, 37 degrees C, 32 degrees C and sham-treated with 37 degrees C. O(2).- current was measured continuously in the right atrium using an electrochemical O(2).- sensor. The O(2).- current increased in all groups except for the sham-treated group during the induction. After the onset of heatstroke, the O(2).- current was suppressed with temperature-dependency. Plasma and liver high-mobility group box 1, intercellular adhesion molecule-1, plasma aspartate aminotransferase and alanine aminotransferase were also suppressed with the suppression of O(2).- generation. Therefore, excessive O(2).- generation might be a key factor in heatstroke and the suppression with moderate hypothermia would be a therapeutic modality.

Anti‐inflammatory signaling during ex vivo liver perfusion improves the preservation of pig liver grafts before transplantation

“…Subnormothermic temperatures have been found to have strong anti‐inflammatory properties similar to the additives described above. In rodent and porcine models, it has been demonstrated that temperatures of 33°C‐34°C reduce Kupffer cell activation and suppress release of IL1, IL6, and TNF‐α . In preliminary studies, we found that the combination of different strategies is most effective to block the activation of proinflammatory pathways during ex vivo perfusion.…”

“…In rodent and porcine models, it has been demonstrated that temperatures of 338C-348C reduce Kupffer cell activation and suppress release of IL1, IL6, and TNF-a. (5)(6)(7)(8) In preliminary studies, we found that the combination of different strategies is most effective to block the activation of proinflammatory pathways during ex vivo perfusion. Therefore, the strategy of our perfusion setup was to combine the benefits of perfusing livers at close to normal temperatures of 338C with the benefits of adding several anti-inflammatory strategies.…”

“…The addition of different anti‐inflammatory agents during ex vivo perfusion might have additional protective effects on the graft besides avoiding cold ischemia injury. In addition, subnormothermic temperatures have strong inhibitory effects on Kupffer cells with a reduction of proinflammatory cytokine release in rodent and porcine models …”

“…In addition, subnormothermic temperatures have strong inhibitory effects on Kupffer cells with a reduction of proinflammatory cytokine release in rodent and porcine models. (5)(6)(7)(8) In the present study, we evaluated if the addition of anti-inflammatory agents plus subnormothermic temperatures improves protective effects of ex vivo organ perfusion on preservation injury in a porcine transplant model.…”

Molecular and Cellular Pathways as a Target of Therapeutic Hypothermia: Pharmacological Aspect

“…Along with the mass screening, traditional studies on the specific target genes have been steadily undertaken. These studies usually focus on genes related with well-known pathways such as cell death or survival [4, 39, 48-50], inflammation [51-57], and free radicals [58-60]. Although inflammation may be a sequel of brain injury as well as infection, injury-related inflammation is a focus of the current reivew.…”