Zenggeng Wang1, Qinghua Wu2, Xiangbi Nie3, Jinghua Guo3, Chunli Yang3. 1. Nanchang University, Nanchang, China; Intensive Care Unit, Jiangxi Provincial People's Hospital, Nanchang, China. 2. Department of Cardiology, Second Affiliated Hospital of Nanchang University, Nanchang, China. Electronic address: ncwqh@163.com. 3. Intensive Care Unit, Jiangxi Provincial People's Hospital, Nanchang, China.
Abstract
BACKGROUND: Myocardial depression, as a well-recognized manifestation of cardiac dysfunction, often accompanies severe sepsis and septic shock. Inflammation-induced myocardial apoptosis is key to the development of sepsis-induced cardiac dysfunction. Increasing evidence suggests the anti-inflammatory role of β1-adrenergic blocker, esmolol, during lethal endotoxemia. However, the direct protective effect of esmolol on cardiomyocyte viability during sepsis is still not clear. Here, we aimed to study whether infusion of esmolol can directly inhibit myocardial apoptosis during lipopolysaccharide (LPS)-triggered inflammatory insult. METHODS: C57BL/6 mice were randomized into four groups as follows: control; esmolol infusion; LPS insult; and esmolol infusion + LPS insult. Function of left ventricle was assessed by invasive hemodynamics at 6 h after LPS insult. Terminal deoxynucleotidyl transferase mediated dUTP nick end labeling (TUNEL) staining, caspase-3 expression level, and the Bcl-2/Bax ratio were used to evaluate myocardial apoptosis at 6 h after LPS insult or esmolol infusion. RESULTS: Administration of LPS resulted in significant decrease in left ventricular end-systolic pressure, reduced maximal rate of change of left ventricular pressure, and the increase in left ventricular end-diastolic pressure. Esmolol infusion reversed LPS-induced impairment of cardiac function and reduced LPS-induced myocardial apoptosis that is associated with c-Jun N-terminal kinase (JNK) and p38 activation. CONCLUSIONS: These data demonstrate that cardioprotection provided by esmolol infusion during LPS insult is associated with antiapoptotic effects and regulation of JNK and p38 activations.
BACKGROUND:Myocardial depression, as a well-recognized manifestation of cardiac dysfunction, often accompanies severe sepsis and septic shock. Inflammation-induced myocardial apoptosis is key to the development of sepsis-induced cardiac dysfunction. Increasing evidence suggests the anti-inflammatory role of β1-adrenergic blocker, esmolol, during lethal endotoxemia. However, the direct protective effect of esmolol on cardiomyocyte viability during sepsis is still not clear. Here, we aimed to study whether infusion of esmolol can directly inhibit myocardial apoptosis during lipopolysaccharide (LPS)-triggered inflammatory insult. METHODS: C57BL/6 mice were randomized into four groups as follows: control; esmolol infusion; LPS insult; and esmolol infusion + LPS insult. Function of left ventricle was assessed by invasive hemodynamics at 6 h after LPS insult. Terminal deoxynucleotidyl transferase mediated dUTP nick end labeling (TUNEL) staining, caspase-3 expression level, and the Bcl-2/Bax ratio were used to evaluate myocardial apoptosis at 6 h after LPS insult or esmolol infusion. RESULTS: Administration of LPS resulted in significant decrease in left ventricular end-systolic pressure, reduced maximal rate of change of left ventricular pressure, and the increase in left ventricular end-diastolic pressure. Esmolol infusion reversed LPS-induced impairment of cardiac function and reduced LPS-induced myocardial apoptosis that is associated with c-Jun N-terminal kinase (JNK) and p38 activation. CONCLUSIONS: These data demonstrate that cardioprotection provided by esmolol infusion during LPS insult is associated with antiapoptotic effects and regulation of JNK and p38 activations.