Externalization and internalization of cardiac endothelin receptors during different phases of sepsis in rat

Objective To study the redistribution of ET1 receptors in two subcellular organelles, the sarcolemmal membrane and the light vesicle, of rat heart during the progress of septic shock Methods Male Sprague Dawley rats weighing from 270 to 320?g were randomly divided into three groups: control, early sepsis, and late sepsis Each group included six rats Sepsis was induced by cecal ligation and puncture (CLP) Control rats were sham operated After operation for 9 hours or 18 hours, animals of the three groups were anesthetized with sodium pentobarbital (60?mg/kg IP) and the hearts were removed for preparation of sarcolemma and light vesicle Hemodynamic parameters were determined with polygraph via femoral artery and intraventricular cannula ET1 receptor was assayed by [ 125 I] ET1 binding Results Heart rate, cardiac output and left ventricular +dp/dt max undergo biphasic changes: an increase in early phase of sepsis (9?h after CLP) followed by a decrease in late phase of sepsis (18?h after CLP) Mean arterial blood pressure and left ventricular dp/dt max remained relatively unaltered during early phase of sepsis but was decreased during late phase of sepsis Although septic rat heart exhibited biphasic cardiodynamic changes, myocardial function showed signs of progressive deterioration during the development of sepsis, as indicated by a progressive elevation of LVEDP [ 125 I] ET1 bindings to cardiac membranes exhibited a saturable process with a single component binding characteristic for all three experimental groups In sarcolemmal membrane fraction, the maximum binding capacity (B max ) calculated from scatchard plot was increased 30% ( P <0 01) during early phase of sepsis but decreased 24% ( P <0 01) during late phase of sepsis The affinity [the reciprocal of the dissociation contant (Kd)] for [ 125 I] ET1 binding in sarcolemmal membranes remained unaffected during early and late phases of sepsis In light vesicle fraction, the B max for [ 125 I] ET1 binding was decreased by 19% ( P <0 05) during early phase of sepsis but increased by 38% ( P <0 01) during late phase of sepsis The affinity for [ 125 I] ET1 binding in light vesicles was unaltered in early and late phases of sepsis It should be mentioned that the sum of Bmax of sarcolemmal and light vesicle fractions was increased by 25% ( P <0 01) during early phase of sepsis but was decreased by 17% ( P <0 01) during late phase of sepsis Conclusions These data indicated that a biphasic intracellular redistribution of ET1 receptor in the heart might contribute to the development of the initial hyperdynamic and subsequent hypodynamic state during sepsis

Effect of bactericidal/permeability increasing protein on sepsis induced by intra abdominal infection in rats

Objective: To investigate the effect and mechanism of bactericidal/permeability increasing protein (BPI) on sepsis induced by intra abdominal infection in rats. Methods: Cecal ligation and puncture (CLP) was made on 20 rats with sepsis induced by intra abdominal infection. BPI or equal volume of physiological saline (PS) was intra abdominally given immediately and 12 h after CLP, respectively (2.5 mg/kg of BPI each time). Plasma endotoxin levels were determined with limulus amebocyte chromogenic assay. Results: (1) The survival time in BPI group was significantly higher than that in PS group. (2) The values of the mean arterial pressure (MAP), the left ventricular systolic pressure (LVSP), the isovolumic ventricular pressure (IP), and the maximal change of left intraventricular pressure (±dp/dtmax) in BPI group, although decreasing, were markedly higher than those in PS group. (3) Plasma glutamic pyruvic transaminase (GPT) and urea nitrogen levels in BPI group, though increasing, were obviously lower than those in PS group. (4) There was no significant change of plasma endotoxin levels in BPI group, while plasma endotoxin levels markedly increased in PS group. Conclusions: BPI has obvious protective effect on sepsis induced by intra abdominal infection, which might be related to its neutralization of endotoxin.