There is now extensive evidence that H2S is an endogenously produced gaseous mediator capable of modulating many pyhsiological process (1). We (2) and others have previously shown that exogenously administered H2S is cardioprotective. A novel organic molecule, GYY4137, is a slow-releasing H2S donor which may be an alternative to the conventional inorganic donor compounds, NaHS and Na2S (3). In the current study, we assessed the effects of GYY4137 on infarct size in a rat heart model of acute myocardial infarction.Methods
Male Sprague Dawley rats (280-350 g) were anaesthetised with sodium pentobarbital (65 mg/kg i.p.) and their hearts were Langendorff perfused. After stabilisation, hearts were subjected to 35 min coronary artery occlusion, followed by 120 min reperfusion. Hearts were treated with GYY4137 1-100 µM, commencing 10 min prior to the onset of coronary occlusion and maintained until 10 min reperfusion. The effects of GYY4137 were compared with ischaemic preconditioning, effected by three 3 min periods of global ischaemia prior to coronary artery occlusion. After 120 min reperfusion, infarct size was measured as percentage of ischaemic zone, using triphenyltetrazolium staining.Results
Data are presented in the table below.Conclusion
GYY4137 limited infarct size in a concentration-dependent manner, maximal at 10 µM. This cardioprotective effect was comparable to IPC. These findings provide evidence for GYY4137 as a cardioprotective agent in ischaemia-reperfusion injury.Conclusion
(1) Elsey DJ et al., Cell Biochem Func 2010;28:95-106. (2) Johanssen D et al., Basic Res Cardiol 2006; 101: 53-60. (3) Li et al., Free Rad Biol Med 2009;47:103-113.