Novel Orally Active Hydrogen Sulfide-Releasing Compound, SG1002, Improves Left Ventricular Function and Survival in a Murine Model of Ischemic Cardiomyopathy

• Main Author: Balan, Bharat
• Format: Others
• Published: VCU Scholars Compass 2017
• Subjects: Ischemic Cardiomyopathy; Adverse Remodeling; Hydrogen Sulfide; SG1002; Heart Failure; H2S; Medical Physiology
• Online Access: http://scholarscompass.vcu.edu/etd/4937; http://scholarscompass.vcu.edu/cgi/viewcontent.cgi?article=6018&context=etd

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.