Therapeutic hypothermia reduces intestinal ischemia/reperfusion injury after cardiac arrest in rats

Abstract

To investigate the effects of therapeutic hypothermia (TH) on the morphology and function of intestine after cardiac arrest and resuscitation, 45 male rats were randomly assigned into three groups: (1) normothermia group, animals underwent ventricular fibrillation (VF) and cardiopulmonary resuscitation (CPR) with the rectal temperature maintained at 36.8 ± 0.2°C until 4 h after return of spontaneous circulation (ROSC); (2) hypothermia group, TH was induced with the aid of ice packs and an electrical fan because VF occurred and was maintained at 33.5 ± 0.5°C for 4 h after ROSC; (3) sham-operated group, animals underwent identical anesthetic and surgical procedures without VF, CPR or defibrillation. Five animals in each group were sacrificed at 4, 24 and 72 h post resuscitation. Serum diamine oxidase (DAO) and apoptosis rate of intestinal epithelial cells were tested by ELISA and flow cytometry, respectively. The concentration of FITC-Dextran that leaked out of enteric cavity was used to analyze the permeability of intestine. Histological changes were graded and compared among the three groups. Serum DAO concentrations in normothermia group reached the peak at 4 h post resuscitation, and then decreased at 24 and 72 h. In comparison with normothermia group, serum DAO concentrations were lower at 4 h in hypothermia group (0.97 ± 0.16 vs. 1.24 ± 0.29, P < 0.05). The amount of FITC-Dextran that passed the wall of small intestine in hypothermia group was signii¬cantly lower than that in normothermia group at 24 h after ROSC (7.81 ± 1.11 vs. 13.07 ± 3.07, P < 0.05). The amount of FITC-Dextran had no difference between normothermia and hypothermia groups at 4 and 72 h post resuscitation. The detached intestinal epithelial cells in hypothermia group showed significant lower frequency of apoptosis than those in normothermia group at 4 h (17.30 ± 2.56 vs. 25.63 ± 4.09, P < 0.05) and 24 h (9.38 ± 1.29 vs. 11.98 ± 1.78, P < 0.05). No obvious injury was observed in both normothermia and hypothermia groups at 4 h with grade of 0 to 1. The histopathological injury in normothermia group reached the peak at 24 h with grade of 2 to 3, which was significantly severe than that in hypothermia group with grade of 1 to 2. At 72 h post resuscitation, an almost complete restitution of the intestinal mucous could be observed both in hypothermia and normothermia groups. This study demonstrates that short term ischemia induced by cardiac arrest and resuscitation resulted in intestinal ischemia/reperfusion (IR) injury, which could be attenuated by therapeutic hypothermia. Key words: Rat, intestine, cardiac arrest, cardiopulmonary resuscitation, therapeutic hypothermia.