Hydrogen sulfide for organ protection

Introduction

Pharmacological and biological actions of the gaseous biological mediator hydrogen sulfide include vasodilatation, cytoprotection, inhibition of mitochondrial respiration as well as induction of a state akin to suspended animation.

Methods

Rodent models of ischemia and reperfusion of the heart and the liver were employed, as well as a model of acute respiratory distress syndrome. A dog model of cardiopulmonary bypass, an ovine model of acute respiratory distress syndrome induced by burn and smoke inhalation as well as a pig model of myocardial infarction were used. Hydrogen sulfide was administered to the animals in a stable, iso-osmolar, pH-neutral intravenous injectable formulation (IK-1001; sodium sulfide for injection).

Results

In a rat study of myocardial infarction, a significant protection was seen in terms of reduction of myocardial infarct size. In a mouse model of myocardial infarction, IK-1001 reduced infarct size, reduced neutrophil infiltration, attenuated the inflammatory response, and improved contractility. The cardiac protection was also confirmed in large animal models: in a porcine model of myocardial ischemia, reduction of infarct size and improvement of cardiac contractility was seen. Improvement of cardiac contractility and preservation of endothelium-dependent relaxant responses were seen in a dog cardiopulmonary bypass model. Protection was also seen in a mouse model of liver ischemia-reperfusion injury. The protective effect of IK-1001 was also demonstrated in a mouse and in a sheep model of acute respiratory distress syndrome, evidenced by improved survival rate, and downregulation of the inflammatory response.

Conclusion

The current presentation overviews some of the recent data demonstrating the organ protective effects of hydrogen sulfide. The mechanism of protection probably involves multiple effects including metabolic effects, antioxidant mechanisms, activation of KATP channels, as well as inhibition of inflammatory cell activation.