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