Protective effect of calcium-sensing receptor inhibitor Calhex231 on traumatic hemorrhagic shock rats

Abstract

Objective To observe the protective effects of calcium-sensing receptor (CaSR) inhibitor Calhex231 on traumatic hemorrhagic shock rats. Methods 144 SD rats were divided into six groups by random number table method: normal group, shock group, lactated Ringer's solution (LR) group, LR+ Calhex231 0.1 mg/kg group, LR+ Calhex231 1 mg/kg group, and LR+ Calhex231 5 mg/kg group, with 16 rats in each group for survival observation and 8 rats for hemodynamics test. 64 SD rats were divided into four groups: normal group, shock group, lactated Ringer's solution (LR) group, LR + Calhex231 1 mg/kg group, with 8 rats in each group for detecting organ blood flow and superior mesenteric artery vascular reactivity and the other 8 rats for mesenteric artery vascular reactivity. After the establishment of traumatic hemorrhagic shock model, the shock group did not receive resuscitation, and the LR group was resuscitated with LR equal to two times of the blood loss volume. The three LR+ Calhex231 groups with different dosages were firstly given LR of equal volume to that of blood loss, and then the Calhex231 was dissolved into LR ( equal to the blood loss volume) to resuscitate. The wound was ligated and sutured immediately after resuscitation. The effect of Calhex231 on animal's 24-hour survival since the beginning of resuscitation was observed. The hemodynamics including the mean arterial blood pressure(MAP), left intraventricular systolic pressure(LVSP), maximal rising, and declining rate of left intraventricular pressure (±dp/dtmax) were observed before shock, at the end of shock, 1 hour after resuscitation, and 2 hours after resuscitation. The effects of Calhex231 on vital organ blood flow and vascular reactivity were observed 2 hours after resuscitation. Results All the shock rats died within 9 hours after the shock model was established. The survival outcomes of LR group rats were slightly improved compared with the shock group rats(P<0.05) . The survival time and 24 hour survival rate of LR+ Calhex231 1 mg/kg group and LR + Calhex231 5 mg/kg group rats were significantly increased compared with the shock group rats (P<0.05). The hemodynamic indexes of LR+ Calhex231 groups were higher than those of the LR group. The best effect was observed in LR + Calhex231 1 mg/kg group rats (P<0.01). The MAP, LVSP and ±dp/dtmax were restored to normal level (64.9%, 82.4%, 89.8%, and 77.8%, respectively). Meanwhile, the blood flow in liver and kidney of LR+ Calhex231 1 mg/kg group rats were increased from 57.2% and 41% to 108.7% and 95.1%, respectively. The vascular reactivity including superior mesenteric artery and mesenteric artery of LR+ Calhex231 1 mg/kg group rats were also increased (P<0.01). Conclusions In rats with hemorrhagic shock, the calcium sensitive receptor inhibitor Calhex231 can improve the vascular reactivity, the hemodynamics, and the blood flow of important organs. It plays a role in protecting the cardiovascular function and reducing the mortality after traumatic hemorrhagic shock. Key words: Receptors, calcium-sensing; Shock, hemorrhagic; Calhex231