Hydrogen Sulfide Attenuates Cardiac Injury in Takotsubo Cardiomyopathy by Alleviating Oxidative Stress

Takotsubo cardiomyopathy (TCM) is characterized by transient left ventricular apical ballooning with the absence of coronary occlusion, which is an acute cardiac syndrome with substantial morbidity and mortality. It was reported that reduced endogenous hydrogen sulfide (HS) levels may be related to various heart diseases. The present study investigated the mechanism by which HS administration modulates and protects cardiac function in TCM rats. In order to establish a TCM model, Sprague Dawley (SD) rats were injected with a single dose of β-adrenergic agonist isoprenaline (ISO). We found that ISO induced cardiac dysfunction, which was characterized by a significant decrease in left ventricular systolic pressure (LVSP), maximum contraction velocity (+dp/dtmax), maximum relaxation velocity (-dp/dtmax) and increased left ventricular end-diastolic pressure (LVEDP). Accordingly, we found that plasma and heart tissue HS levels in TCM rats decreased significantly, and cardiac cystathionine γ-lyase (CSE) and 3-mercaptopyruvate sulfurtransferase (3-MST) expression were lower. Moreover, cardiac dysfunction in TCM was associated with oxidative stress response and reactive oxygen species (ROS) formation. NADPH Oxidase 4 (NOX) and p67 protein expressions significantly increased in TCM cardiac tissues. In addition, Sodium hydrosulfide (NaHS) ameliorated ISO-induced cardiac dysfunction and reversed ISO-induced oxidative stress. This study revealed that HS exerted cardioprotective effects by reducing NADPH oxidase, which reduced ROS formation and prevented oxidative stress. Our study provided novel evidence that HS is protective in myocardial dysfunction in TCM rats and could be a therapeutic target for alleviating β-adrenergic system overstimulation-induced cardiovascular dysfunction.