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.

Overexpression of miR-150-5p Alleviates Apoptosis in Sepsis-Induced Myocardial Depression

“…As mentioned previously [ 2 , 12 ], our group has found that there is a positive relationship between the MAP and heart function. In this study, septic shock occurred at approximately 2 hours after LPS injection, and the MAP of the control groups remained unchanged ( Figure 1(a) ).…”

“…Briefly, male adolescent rats (Changsheng Bio, Benxi, China) weighing 170 g to 190 g were anesthetized with 20% urethane (1 g/kg, 1 g urethane was added to 5 mL 0.9% saline). We separated the left femoral artery and connected it to the electrophysiological recorder (Biopac MP150 Biopac Systems, Goleta, CA, USA) to monitor the pressure and injected LPS intraperitoneally to establish the model (20 mg/kg, 10 mg LPS was added to 1 mL 0.9% saline) (Escherichia coli 055: B5, L-2880, Sigma-Aldrich, St. Louis, MO, USA) [ 2 ]. Control rats were treated with an equal volume of saline.…”

“…Sepsis is a syndrome of physiological, pathological, and biochemical abnormalities caused by the altered systemic host response to infection [ 1 ]. Septic shock is a subset of sepsis in which the underlying circulatory and metabolic abnormalities are profound enough to substantially increase mortality [ 2 ]. Heart dysfunction [ 3 ] often occurs in septic patients and is referred to as sepsis-induced myocardial depression, which is an important cause of septic shock and increased mortality.…”

Characterization of Long Noncoding RNA and mRNA Profiles in Sepsis-Induced Myocardial Depression

“…Our previous study showed that there is a positive relationship between mean arterial pressure (MAP) and heart function 10 . Therefore, we measured MAP and found that MAP started to decline approximately 1.5 h after the administration of LPS.…”

“…All experiments conformed to all relevant regulatory standards. The adolescent rat model of septic shock was generated by intraperitoneal injection of LPS, as in our previous description 10 . Briefly, male pathogen-free Wistar rats from Changsheng Bio (Benxi, China) weighing from 170 to 190 g were anesthetized by 20% urethane (1 g/kg i.p.).…”