tropisetron and Sepsis

The objective of the present investigation was to explore the possible effect of the 5-HT3 receptor antagonist tropisetron on the expression levels of the inflammatory factors interleukin 6 (IL-6), creatine kinase isoenzyme (CK-MB), soluble growth stimulating gene 2 protein (sST2) and immunoglobulin E (IgE), as well as the cardiac action potential in septic rats.. The cecal ligation and perforation (CLP) method was utilized to construct abdominal infarction in rats. A total of 68 male adult Sprague Dawley rats were used, including 40 for assessing survival and 28 for detecting the expression levels of IL-6 and IgE, myocardial injury, cardiac dysfunction and the cardiac action potential. These 28 rats were divided into the sham (6 rats), sham + Tropisetron (6 rats), CLP (8 rats) and CLP + Tropisetron (8 rats) groups. Twenty-four hours after establishment of the sepsis rat model, immunohistochemistry was used to analyze 5-HT3 receptor protein expression, and enzyme-linked immunosorbent assay (ELISA) was employed to monitor the serum levels of IL-6, CKMB, sST2 and IgE. Furthermore, the structure of the myocardium in various groups was examined by H&E staining.. The levels of IL-6, CK-MB, sST2 and IgE in the sepsis group were significantly higher than those of the sham group (P <  0.01). Furthermore, the heart rate in the sepsis group was lower than that of the sham group (P <  0.01), and the time of atrial ventricular action potential in the sepsis group was longer than that of the sham group (P <  0.05). In addition, immunohistochemical analyses showed that the area, intensity and index of 5-HT3 receptor in the sepsis group were significantly lower than those of the sham group (P <  0.01). Importantly, the 5-HT3 receptor antagonist Tropisetron exhibited significant inhibitory effects IL-6, CK-MB, sST2 and IgE expression levels, and inductive effects on atrial ventricular action potential in the sepsis group.. Sepsis leads to systemic inflammatory reaction, resulting in myocardial injury, structural changes and immune imbalance. The inhibitory effect of tropisetron on inflammation, and the regulatory inflammatory disorder by the efferent vagus nerve may be one of the important mechanisms leading to cardiac electrophysiological changes in sepsis.

Topics: Action Potentials; Animals; Disease Models, Animal; Heart; Inflammation; Inflammation Mediators; Isolated Heart Preparation; Male; Rats; Rats, Sprague-Dawley; Sepsis; Serotonin 5-HT3 Receptor Antagonists; Tropisetron

A 5-HT(3) receptor antagonist, tropisetron, has been reported to exhibit an anti-inflammatory effect in chronic inflammatory diseases by antagonizing a particular subtype of serotonin receptors. We investigated whether overproduction of cytokines could be controlled by intervention with tropisetron in an animal model of sepsis and also examined the effects of tropisetron on autonomic nervous activity.. Sixty-eight adult male Sprague-Dawley rats were used (28 for examination of cytokine production and autonomic nervous activity; 40 for survival analysis). Each part of the study involved 4 animal groups, including two control groups without drug administration. Sepsis was induced by cecal ligation and puncture (CLP). Tropisetron hydrochloride (1mg/kg) was administered immediately after surgery. Continuous electrocardiograms were recorded for 5 min before and 1, 2, 4, and 6h after surgery in CLP and sham-operated animals for heart rate variability (HRV) analysis. Blood samples were collected 6h after surgery for serum cytokine and catecholamine assay.. HRV analysis demonstrated a significant increase in LF/(LF+HF) in the CLP animals compared with the sham-operated animals, regardless of tropisetron administration, indicating induction of sympathetic overstimulation. Tropisetron significantly inhibited IL-6 induction in the CLP animals (p<0.01). Although it did not significantly change HRV parameters, tropisetron significantly inhibited increase in serum level of noradrenaline (p<0.05). Tropisetron did not significantly improve CLP animal survival rate.. Intervention with a 5-HT(3) receptor antagonist can control excess cytokine production involved in the pathogenesis of severe sepsis/septic shock.

Topics: Animals; Autonomic Nervous System; Catecholamines; Cytokines; Disease Models, Animal; Electrocardiography; Heart Rate; Indoles; Male; Rats; Rats, Sprague-Dawley; Sepsis; Serotonin Antagonists; Treatment Outcome; Tropisetron