Elsevier

Life Sciences

Volume 93, Issue 1, 19 July 2013, Pages 24-29
Life Sciences

Effects of sodium hydrosulfide on intestinal mucosal injury in a rat model of cardiac arrest and cardiopulmonary resuscitation

https://doi.org/10.1016/j.lfs.2013.05.012Get rights and content

Abstract

Aims

Cardiac arrest and cardiopulmonary resuscitation (CPR) can lead to intestinal ischemia/reperfusion (I/R) injury. Increasing studies have indicated that hydrogen sulfide (H2S) is in favor of a variety of tissue I/R injury. The purpose of this study was to explore whether sodium hydrosulfide (NaHS), a H2S donor, can protect intestinal mucosa after CPR and its potential mechanisms.

Main methods

Male Sprague–Dawley rats were subjected to 6 min cardiac arrest induced by transcutaneous electrical epicardium stimulation and then resuscitated successfully. A bolus of either NaHS (0.5 mg/kg) or placebo (NaCl 0.9%) was blindly injected 1 min before the start of CPR intravenously, followed by a continuous injection of NaHS (2 mg/kg/h) or placebo for 3 h. Intestinal and plasma samples were collected for assessments 24 h after CPR.

Key findings

We found that NaHS can markedly alleviate cardiac arrest induced intestinal mucosal injury. Rats treated with NaHS showed a lower malondialdehyde content, higher superoxide dismutase activity and glutathione content in intestine after CPR. Increased intestinal myeloperoxidase activity was significantly decreased by NaHS after CPR. Moreover, a reduced intestinal apoptotic cells after CPR were evident when pretreated with NaHS. Further studies indicated that NaHS enhances the expression of hypoxia-inducible factor-1α (HIF-1α) in intestine after CPR.

Significance

Our data demonstrated that NaHS treatment before CPR induces intestinal mucosal protection 24 h post-resuscitation. The protective effects may be through oxidative stress reduction, inflammation alleviation, apoptosis inhibition and HIF-1α activation.

Introduction

When cardiac arrest occurs, blood flow and oxygen delivery are abruptly halted. Even after successful cardiopulmonary resuscitation (CPR), because of myocardial dysfunction, hemodynamic instability and microvascular dysfunction, inadequate blood flow and tissue oxygen delivery still persist. These factors may lead to systemic ischemia/reperfusion (I/R) injury in various organs (Nolan et al., 2008). Many studies have focused on heart and brain dysfunctions, while intestine is equally or even more sensitive to ischemia than brain or muscle after CPR (Korth et al., 2003). I/R in intestine increases intestinal barrier permeability and results in the translocation of pathogenic bacteria and endotoxins. Eventually, it will develop to sepsis and multiple organ failure.

As the third member in the gasotransmitter family, hydrogen sulfide (H2S) exerts a variety of physiological effects in biological systems. More and more studies found that administration of H2S donor (sodium hydrosulfide (NaHS) or sodium sulfide (Na2S)) can protect various organs against I/R injury (Nicholson and Calvert, 2010). Along these lines, previous studies have demonstrated that Na2S can improve survival, reduce sensorimotor deficit and prevent water diffusion abnormality in the brain after CPR (Minamishima et al., 2009, Knapp et al., 2011, Kida et al., 2012). However, till now, there is scarcity of data about the impact of H2S on intestinal mucosal injury after CPR.

Therefore, in this study, we aimed to investigate the effects of NaHS on intestinal mucosal injury after CPR and the possible underlying mechanisms.

Section snippets

Animals

Male Sprague–Dawley rats (weight 400–500 g, Animal Experimental Center of Tongji College of Huazhong University of Science and Technology) received humane care in compliance with the Guidance Suggestions for the Care and Use of Laboratory Animals, formulated by the Ministry of Science and Technology of the People's Republic of China. Experimental procedures were approved by the Animal Care and Use Committee of Huazhong University of Science and Technology.

Experimental procedures

Rats were randomly divided into 3

NaHS protects intestinal permeability and integrity after CPR

As shown in Fig. 1A, relative to sham treated controls, the intestinal permeability was markedly increased (12.42 ± 1.07 versus 0.91 ± 0.17 μg/ml, P < 0.01) after CPR. Rats treated with NaHS showed a significant reduction (6.55 ± 1.24 μg/ml, P < 0.01) in the leakage of FITC-dextran across the intestinal wall when compared with the CPR group. The DAO activity in plasma from sham operated rats averaged 495.67 ± 18.53 U/l, while rats subjected only to CPR were found to have 897.43 ± 36.52 U/l (P < 0.01, Fig. 1B).

Discussion

Cardiac arrest is a serious hypoxic process which can cause a prolonged, up to 60 min reduction of blood flow in the intestinal wall (Korth et al., 2003). The intestinal epithelium is an important barrier which is sensitive to reduced flow and tissue hypoxia. In the present study, we determined intestinal permeability, plasma DAO activity and Chiu score, so as to investigate the impairment degree of intestinal mucosa 24 h after CPR. Intestinal permeability is a parameter of mucosal dysfunction,

Conclusion

In the present study, we found that administration of NaHS before CPR reduced intestinal mucosal injury 24 h after CPR associated with attenuation of oxidative stress, inflammation, apoptosis and increased HIF-1α expression. Our findings provide further clues to elucidate that NaHS has the therapeutic potential for multiple organ injury after CPR and will help researchers to understand the mechanism by which NaHS exerts its protection on cell survival after CPR.

Conflict of interest statement

The authors declare that there are no conflicts of interest.

Acknowledgments

This work was supported by grants from National Natural Science Foundation of China (No. 81071526, No. 81272063).

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