Anti-inflammatory effect of hydrogen-rich saline in a rat model of regional myocardial ischemia and reperfusion
Introduction
Acute myocardial infarction (AMI) is a potentially fatal event. Restoring blood flow is the most effective and important therapy for AMI at present [1]. Although blood flow restoration is critical, reintroduction of molecule oxygen often triggers a cytotoxic cascade, during which reactive oxygen species drives downstream signal networks leading to both cell death (or apoptosis) and inflammation [2], [3], [4]. As the human heart has a low regenerative ability, the inflammatory response and cytokines released from the myocardium play an important role in cardiac repair and the pathophysiological response to I/R injury [5]. In many studies [6], [7], [8], [9], acute inflammatory reaction is regard as a mediator of ischemia-reperfusion (I/R) injury. It is known that methods that reduce levels of inflammatory cytokines [10] or infiltration of leukocytes [11] can attenuate reperfusion-induced myocardial damage. However, there is a lack of well recognized methods to ameliorate the inflammatory response during reperfusion [12].
Hydrogen, a highly flammable gas, has proved to be protective against I/R injury to various organs including the brain [13], [14], intestine [15], liver [16] and heart [17] through inhibition of oxidant stress. A recent study [18] reported that ingestion of H2-water also has an anti-inflammatory effect and could efficiently suppress dextran sodium sulfate (DSS)-induced colitis through its anti-inflammatory effect. In our previous study [19], we found that hydrogen-rich saline, which is safe, economical and easily available, had a cardioprotective effect against myocardial I/R injury in rats through the anti-oxidative stress and apoptotic pathways. However, it is unclear whether H2 saline could efficiently decrease the inflammatory response in myocardial I/R injury. To test this, we measured a variety of parameters related to inflammatory response, infarct size and heart function in a regional myocardial I/R rat model after administration of H2 saline, and demonstrated that it had a potent anti-inflammatory effect.
Section snippets
Animals
Adult male Sprague–Dawley rats weighing 250–280 g (Experimental Animal Center of the Second Military Medical University, Shanghai, China) were housed with free access to food and water under a natural day/night cycle, and acclimated for 7 days before any experimental procedure. All experimental procedures were approved by the Institutional Animal Care and Use Committee of the Second Military Medical University.
H2 saline production
Hydrogen was dissolved in 0.9% saline for 6 h under a high pressure (0.4 MPa) to a
Hemodynamic measurements
As shown in Table 1, intraperitoneal injection of H2 saline decreased I/R-induced degradation of the hemodynamic parameters including LVSP, LVEDP, +(dP/dt)max and −(dP/dt)max. All the hemodynamic parameters in both control group and H2 group were significantly lower than those in the sham group. No significant difference was seen in the heart rate after 24-h I/R between 3 groups.
Measurement of infarct size
The infarct size in H2 group was significantly smaller than that in control group (*P < 0.05) (Fig. 1). There was no
Dicussion
This is the first study demonstrating that H2 saline had an anti-inflammatory effect in a rat model subjected to regional myocardial I/R injury, and this anti-inflammatory effect may play an important role in the cardioprotection of H2 saline. In the present study, we detected the levels of infarct size and inflammatory cytokines after 24-h reperfusion, because they are relatively stable at this time point and 24-h after reperfusion is the peak of inflammatory reaction according to our previous
Acknowledgements
Authors thank Li Zhu and Zhang Peng for their help in writing this paper [31].
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Yufeng Zhang and Qiang Sun contributed equally to this work.