Hydrogen sulfide (H2S) is the newest member of the gasotransmitter family and is becoming well known for its cardioprotective effects in preclinical trials. Many recent studies have shown the benefits of exogenous H2S in the setting of acute myocardial infarction (AMI) and pressure overload-induced heart failure, but current formulations are derived from inorganic salts which have shortcomings in the precision and control of release of H2S. The main objective of this thesis was to determine if the novel, orally active, slow-releasing compound, SG1002, can attenuate the severity of damage and adverse remodeling caused by ischemia/reperfusion injury through an induction of angiogenesis. A traditional sodium salt, Na2S, which has been previously shown to be cardioprotective, was used as a positive control. SG1002 improved overall left ventricular function as measured by increased ejection fraction from echocardiography and decreased QRS interval from electrocardiography compared to untreated animals following MI. SG1002 therapy was also associated with an induction of angiogenesis, which was determined through qRT-PCR, western blot, and histological methods. SG1002 increased VEGF protein levels, which was paralleled with an increase in capillary density in the infarct region. SG1002 also upregulated microRNA-126, which is thought to repress the inhibitor of VEGF, Spred-1. It is possible that this “angiomiR” plays a key role in the angiogenesis-related cardioprotection of H2S. The combination of increased pro-angiogenic factors along with greater vascular density resulting from SG1002 therapy indicates the therapeutic potential for this drug in the prevention and/or treatment of ischemic heart failure.

Hydrogen sulfide (H2S) is a gasotransmitter that has shown cardioprotective effects in the setting of myocardial injury such as acute myocardial infarction (MI) and pressure overload-induced heart failure. However, there are shortcomings in precision and control release from the use of traditional formulations of H2S in the form of inorganic salts. In this thesis, we sought to determine if the novel, orally active, slow-releasing H2S-compound SG1002 plays a role in attenuating MI-induced left ventricular (LV) dysfunction and adverse remodeling. We also evaluated the effect of SG1002 on changes in ECG parameters such as QT interval, in addition to 28-day survival post MI. SG1002 protects against ischemic cardiomyopathy in mice by mitigating LV dysfunction as measured by echocardiography and decreasing LV scar size as measured by histopathological methods. The improvement in survival might be due to the reduction in QT interval prolongation hence lessening the likelihood of forming lethal arrhythmias post MI. Western blot analyses of SG1002 treated mice showed restoration of VEGF levels indicating a pivotal role played by pro-angiogenic signaling in the improvement of cardiac function and attenuation of adverse remodeling. We propose that SG1002 can be a promising pharmacotherapeutic means for the treatment of ischemic heart failure.