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.
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.
These data demonstrate that cardioprotection provided by esmolol infusion during LPS insult is associated with antiapoptotic effects and regulation of JNK and p38 activations.