COMPARISON OF THE PROTECTIVE EFFECT OF DIFFERENT MILD THERAPEUTIC HYPOTHERMIA TEMPERATURES ON INTESTINAL INJURY AFTER CARDIOPULMONARY RESUSCITATION IN RATS

摘要

Background: Therapeutic temperature management (TTM) is the standard treatment protocol for unconscious post-resuscitation patients. However, there is still controversy about the ideal targeted temperature of mild hypothermia therapy. Additionally, studies about protective therapy for post-resuscitation intestinal injury are very limited. Therefore, this study was performed to explore: whether mild hypothermia therapy can exert a protective effect on post-resuscitation intestinal injury; the protective effect of different targeted temperatures on post-resuscitation intestinal injury and the ideal targeted temperature; the potential protective mechanism of mild hypothermia therapy for post-resuscitation intestinal injury. Methods: Ventricular fibrillation was electrically induced and untreated for 6min while defibrillation was attempted after 8 min of cardiopulmonary resuscitation in 15 rats. After successful resuscitation, animals were randomized into three groups: control; TTM-35; TTM-33. In animals of the control group, temperature was maintained at 37±0.2℃ for 6 h. In animals of the two TTM groups, temperature was maintained at 33 ± 0.28C or 35 ± 0.28C for 6 h, respectively. During mild hypothermia therapy, intestinal microcirculation was measured at 60, 240, and 360 min after resuscitation. Animals were euthanized 6.5 h after resuscitation. The morphological changes in the intestinal tissue, systemic and local inflammatory factors, and intestinal injury markers were measured and analyzed. The tight junction proteins in the intestinal epithelium, cell-cell contact protein E-cadherin expression, myosin light chain (MLC) and myosin light chain kinase levels, and the NF-kB p65 signaling pathway were analyzed by western blotting. Results: Compared with results in the control group, mild hypothermia therapy (TTM-33 and TTM-35 groups) significantly improved post-resuscitation intestinal micro-circulation and pathological scores, decreased systemic and local intestinal tissue inflammatory factor levels, inhibited the NF-kB signaling pathway and downstream MLC phosphorylation, and significantly decreased MLC phosphorylation-associated loss of intestinal tight junction proteins and E-cadherin (P< 0.05). A 338C target temperature could exert more protective effects than 358C on post-resuscitation intestinal injury, such as improving intestinal microcirculation, decreasing intestinal ischemia factor iFABP, and plasma endotoxin levels, inhibiting the NF-kB signaling pathway and downstream MLC phosphorylation, and suppressing the loss of intestinal tight junctions and E-cadherin (P<0.05). Conclusions: Mild hypothermia therapy can improve post-resuscitation intestinal injury, and a targeted temperature of 338C may confer more benefit for mitigation of intestinal injury as compared with a targeted temperature of 358C.