The Trend of β3-Adrenergic Receptor in the Development of Septic Myocardial Depression: A Lipopolysaccharide-Induced Rat Septic Shock Model

Abstract

Septic shock with low cardiac output is very common in children. However, the mechanism underlying myocardial depression is unclear. The role of β₃-AR in the development of myocardial depression in sepsis is unknown. In the present study, we generated an adolescent rat model of hypodynamic septic shock induced by lipopolysaccharide (LPS). Neonatal cardiomyocytes were also treated with LPS to mimic myocardial depression in sepsis, which was confirmed via an in vivo left ventricular hemodynamic study, and measurements of contractility and the Ca²⁺ transient in isolated adolescent and neonatal cardiomyocytes. After 16 h of LPS treatment, cultured neonatal cardiomyocytes showed a diminished Ca²⁺ transient amplitude associated with an increase in the β₃-AR level. With the addition of a β₃-AR agonist, the Ca²⁺ transient in LPS-treated neonatal rat cardiomyocytes gradually decreased over time; such a change was absent in cells treated with nitric oxide synthase (NOS) inhibitors prior to treatment with a β₃-AR agonist. In adolescent rats with septic myocardial depression, cardiac function declined as indicated by decreased MAP, dP/dt_max, and dP/dt_mix for 6 h after LPS injection; however, the β₃-AR level first increased 2 h after LPS treatment and then decreased 6 h after LPS treatment in the absence of exogenous catecholamines. The results indicate that, in vitro, at the cellular level β₃-AR may be involved in the development of myocardial depression (Ca²⁺ transient depression) in sepsis through NOS signaling pathways; however, in vivo, a complicated mechanism for modulating β₃-AR may exist.