title: Alterations in the myocardial β-adrenergic system during experimental endotoxemia.
abstract: In this study to investigate whether β-adrenergic receptor systems in the heart are impaired during endotoxemia, we examined two models of septic shock in rats, each of which has a different time course for the shock state. Male Wistar rats were divided into two groups: (1) the LPS (lipopolysaccharide) iv group (Escherichia coli endotoxin 1.0 mg·kg(-1) iv bolus administration), and (2) the CLP (cecal ligation and puncture model) group. As a control group for each model, a 0.9% saline injection group and a sham-operated group were also prepared. At 3, 12, and 24 h after treatment, the rats were killed and their hearts were removed as rapidly as possible. In the LPS iv and CLP groups, an increase in the plasma epinephrine (E) and norepinephrine (NE) levels compared with the control and sham-operated groups was observed at both 3 and 12h after treatment (P<0.05). There was a decrease in myocardial tissue NE concentration at 3, 12 and 24h in the CLP group. This decrease was especially marked at 24h. In the LPS iv group, a decrease in β-receptor density was observed at 3 h (control, 87.07±4.59 fmol·mg(-1) protein; LPS iv, 60.73±3.51 fmol·mg(-1) protein), but was not observed at 24h. In contrast, a decrease in β-receptor density in the CLP group was observed at 24h (sham-operated, 80.9±3.65 fmol·mg(-1) protein; CLP, 66.1±4.08 fmol·mg(-1) protein), but was not observed at 3h. The β-receptor density in the hearts of LPS iv rats and the altered hemodynamics recovered in line with the decrease in plasma catecholamines (CA). However, in the CLP group the alteration in hemodynamics was not in line with plasma CA. The alteration in hemodynamics of septic-shock rats observed in this study was linked to the change in heart β-receptor density rather than the change in plasma CA. These observations suggested that the alterations which occur in the β-receptor system during endotoxemia depend upon the model of animal sepsis that is employed, and the time course of the septic-shock state. These alterations in the β-adrenergic system are thought to cause myocardial dysfunction during endotoxemia.
authors.affiliation: Department of Anesthesiology and Reanimatology, Gunma University School of Medicine, 3-39-22 Showa-machi, Maebashi, 371, Gunma, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Kadoi
authors.forename: S
authors.initials: S
authors.lastname: Saito
authors.forename: N
authors.initials: N
authors.lastname: Fujita
authors.forename: T
authors.initials: T
authors.lastname: Morita
authors.forename: T
authors.initials: T
authors.lastname: Fujita