The role of gap-junction in suspended animation for hemorrhagic shock with brain injury: experiment with rats

Abstract

To investigate the role of gap-junction in suspended animation for hemorrhagic shock with brain injury. Twenty-four SD rats were made into models of uncontrolled hemorrhagic shock and occlusion of bilateral common carotid arteries and randomly divided into 3 equal groups: traditional resuscitation group (Group I) undergoing traditional resuscitation, hypothermy resuscitation group (Group II) undergoing temperature lowering by ice-cap, and carbenoxolone resuscitation group (Group III) undergoing injection of carbenoxolone 50 microg/200 g. The process was divided into 3 periods: traumatic hemorrhagic period (30 min), pre-hospital treatment period (60 min), and in-hospital cardiopulmonary resuscitation period (60 min). The levels of left ventricular systolic pressure (LVSP), maximum change rate of left ventricular pressure rise and fall (+/- dp/dt(max)), mean arterial pressure (MAP), heart rate (HR), and respiratory rate (RR) were recorded at the beginning and the end of traumatic hemorrhagic period (T1 and T2), the end of pre-hospital treatment period (T3), and the end of in-hospital cardiopulmonary resuscitation period (T4). The survival time was recorded after in-hospital cardiopulmonary resuscitation period. Then the left brain was taken out and the hippocampal neurons apoptosis was observed by flow cytometry, chemiluminescence was used to detect the ATP, and IL-6 and tumor necrosis factor (TNF)-alpha were detected by enzyme linked immunosorbent assay (ELISA). The survival time of Groups II and III were (2.9 +/- 0.6) h and (2.6 +/- 1.0) h respectively, both significantly longer than that of Group I [(1.4 +/- 0.3) h, both P < 0.01]. The apoptotic rates of hippocampal neurons of Groups II and III were (72 +/- 6)% and (75 +/- 9)% respectively, both significantly lower than that of Group [83 +/- 5)% P < 0.05]. The ATP levels in hippocampus of Groups II and III were (2.0 +/- 0.3) and (1.9 +/- 0.4) pg/g respectively, both significantly higher than that of Group I [(1.4 +/- 0.5 pg/g, both P < 0.05). The TNF-alpha and IL-6 levels of Groups II were (1.7 +/- 0.3) pg/g and (19 +/- 3) pg/g respectively, both significantly lower than those of Group I [(2.2 +/- 0.6) and (24 +/- 3) pg/g respectively, both P < 0.05]. The IL-6 level of Group III was (26 +/- 4) pg/g, significantly higher than that of Group II (P < 0. 01). There were no significant difference between Groups II and III in the values of survival time, hippocampal neuron apoptosis, dissipation of ATP, and liberation of TNF-alpha (all P > 0.05), but there was significant difference in IL-6 (P < 0.01). Both hypothermy resuscitation and carbenoxolone resuscitation protect the brain of cerebral ischemia on hemorrhagic shock with brain injury, and suggest that Gap junctions play an important role in suspended animation to treat hemorrhagic shock with brain injury.