Rao P S, Cavanagh D, Graham D, Graham L B, Dietz J R, Fiorica J V, Hoffman M S
Department of Obstetrics and Gynecology, University of South Florida College of Medicine, Tampa 33612, USA.
Am J Obstet Gynecol. 1998 Jul;179(1):21-7. doi: 10.1016/s0002-9378(98)70246-7.
We evaluated the effects of coliform endotoxin on the circulating levels of atrial natriuretic factor and renal function. To understand the direct effects of endotoxin in the release of atrial natriuretic factor by cardiac tissue, studies in isolated rat atria were performed.
In vivo studies were used. Anesthetized dogs were studied, with one group receiving isotonic saline solution (n = 6) and the other group receiving 50 microg/kg of coliform endotoxin (n = 7) as a continuous infusion over a 4-hour period. Cardiovascular parameters, renal function, and circulating levels of atrial natriuretic factor were measured at specified time intervals. In another set of experiments with in vitro studies left atria from Sprague-Dawley rats were isolated and perfused. In the control group (n = 9) the standard Krebs perfusate was used. In the endotoxin group (n = 9) coliform endotoxin was added at a concentration of 250 microg/mL to the standard perfusate. Atrial pressure was used as an index of stretch, and atrial natriuretic factor was measured from the perfusate.
Administration of endotoxin resulted in decreased blood pressure (P < .05) with a concomitant increase in heart rate. Renal artery flow, however, showed an increase (P < .05) initially followed by a return to its baseline value, with a sustained increase occurring in the saline solution control group. A significant (P < .05) and sustained increase in the circulating levels of atrial natriuretic factor after endotoxin infusion did not prevent the decrease in fractional sodium excretion (P < .05) and creatinine clearance despite an increase in the urinary output. Serum sodium, serum potassium, and osmolalities, however, remained relatively stable. The study pertaining to isolated atria showed that in the presence of low atrial pressures, addition of endotoxin had no significant effect on the release of atrial natriuretic factor. With the increase in atrial pressure atrial natriuretic factor release was significantly higher in the group directly exposed to endotoxin compared with the control group.
These studies demonstrate that the slow infusion of coliform endotoxin results in increased circulating levels of atrial natriuretic factor. This increase is in part due to the direct effect of endotoxin on the heart as indicated by studies in isolated atria. Our data suggest that atrial natriuretic factor in endotoxemia acts in an integrative manner with other hormones on a variety of target organs to modulate cardiovascular function and fluid balance.
我们评估了大肠菌群内毒素对心房利钠因子循环水平和肾功能的影响。为了解内毒素对心脏组织释放心房利钠因子的直接作用，我们进行了离体大鼠心房的研究。
采用体内研究。对麻醉犬进行研究，一组接受等渗盐溶液（n = 6），另一组接受50微克/千克的大肠菌群内毒素（n = 7），持续输注4小时。在特定时间间隔测量心血管参数、肾功能和心房利钠因子的循环水平。在另一组体外研究实验中，分离并灌注Sprague-Dawley大鼠的左心房。对照组（n = 9）使用标准的Krebs灌注液。在内毒素组（n = 9）中，将大肠菌群内毒素以250微克/毫升的浓度加入标准灌注液中。将心房压力用作牵张指标，并从灌注液中测量心房利钠因子。
给予内毒素导致血压下降（P <.05），同时心率增加。然而，肾动脉血流量最初增加（P <.05），随后恢复到基线值，而生理盐水对照组则持续增加。尽管尿量增加，但内毒素输注后心房利钠因子循环水平显著（P <.05）且持续增加并不能阻止钠排泄分数（P <.05）和肌酐清除率的下降。然而，血清钠、血清钾和渗透压保持相对稳定。关于离体心房的研究表明，在低心房压力下，添加内毒素对心房利钠因子的释放没有显著影响。随着心房压力的增加，直接暴露于内毒素的组与对照组相比，心房利钠因子释放显著更高。
这些研究表明，缓慢输注大肠菌群内毒素会导致心房利钠因子循环水平升高。如离体心房研究所示，这种升高部分是由于内毒素对心脏的直接作用。我们的数据表明，内毒素血症中的心房利钠因子与其他激素以整合方式作用于多种靶器官，以调节心血管功能和液体平衡。
