atrial-natriuretic-factor and Toxemia

We have previously reported an increase in plasma levels of atrial natriuretic factor (ANF) in an ovine model of endotoxemia. The purpose of this study was to determine if this IR-ANF release was mediated by the increase of right atrial pressure (RAP) and right heart volumes concomitantly observed following endotoxin (LPS) administration. We studied right ventricular function, renal blood flow (RBF), urinary output (UO), urinary clearance of free water (CH20), urinary osmolality (UOSM), sodium excretion (UENA), and the plasma IR-ANF concentration (radioimmunoassay), following the administration of an E. coli LPS bolus (1 microgram/kg) with (group O, n = 8) and without (group E, n = 10) pretreatment with OKY-046, a selective thromboxane synthetase inhibitor. LPS induced early increases in RAP, right ventricular end-systolic (RVESV) and end-diastolic (RVEDV) volumes, heart rate (HR), and IR-ANF, and delayed increases in RBF, UO, and CH20. OKY-046 prevented the elevation of RAP, RVEDV, and RVESV; however, both groups showed virtually identical increases in IR-ANF (E: 20.03 +/- 3.8 to 192.33 +/- 35.47 pg/ml, O: 17.9 +/- 4.1 to 159.5 +/- 23 pg/ml) as well as an increase of HR, RBF, UO, and CH20. The increase in IR-ANF release noted following the administration of LPS in an ovine model does not appear to be related to the early elevations in right heart volumes or atrial distension.

Topics: Animals; Atrial Natriuretic Factor; Blood Pressure; Cardiac Output; Disease Models, Animal; Diuresis; Endotoxins; Heart Rate; Lipopolysaccharides; Methacrylates; Natriuresis; Osmolar Concentration; Renal Circulation; Sheep; Thromboxane-A Synthase; Toxemia; Urine; Vascular Resistance; Ventricular Function, Right

We used a chronic instrumented ovine model to investigate right heart function following an endotoxin bolus. Primary aim of the experiments was to elucidate the influence of the right heart on the cardiopulmonary system. Furthermore, we tried a thromboxane synthetase inhibitor as a therapeutical approach. At least we investigated the IR-ANF release, as the endocrinal function of the right heart, in this model. Following the endotoxin administration we observed a massive increase of the pulmonary arterial pressure. As a result of the increased right ventricular afterload right ventricular ejection fraction decreased and end-systolic volume increased. Impaired right heart function could not be compensated sufficiently using Frank Starling mechanism. Consequently, decreased left ventricular preload, stroke volume and cardiac output followed. Pretreatment with OKY-046, a selective thromboxane synthase inhibitor, attenuated the increase in pulmonary arterial pressure and prevented the early right heart failure including the drop of cardiac output. Furthermore, OKY-046 changed the thromboxane-prostacyclin relationship. Therefore we consider the cardiopulmonary reactions following pretreatment with OKY-046 as a result of the attenuated right ventricular afterload as well as of the increased prostacyclin concentration. Endotoxin induced hypoxaemia could not be prevented by pretreatment with OKY-046 and might be caused by interstitial edema following endothelial leakage. IR-ANF release in our model, accompanied by polyuria and natriuresis, seemed to be independent of right heart dysfunction and increase of right atrial pressure. We suggest endotoxin or a endotoxin induced mediator as a trigger of IR-ANF release.

Topics: Animals; Atrial Natriuretic Factor; Endotoxins; Escherichia coli; Heart Function Tests; Hemodynamics; Kidney; Methacrylates; Pulmonary Circulation; Pulmonary Wedge Pressure; Sheep; Thromboxane-A Synthase; Toxemia; Ventricular Function, Right

A bolus of Escherichia coli endotoxin (1.5 micrograms/kg) was administered to chronically instrumented sheep. Immunoreactive atrial natriuretic factor (IR-ANF) was measured in extracted plasma by radioimmunoassay. There was a thirteenfold increase in IR-ANF 2 h after endotoxin administration, and IR-ANF levels remained significantly elevated during the first 6 h. A marked diuresis and natriuresis occurred between 4 and 6 h. ANF not only affects renal function but is also associated with decreased cardiac output, increased peripheral resistance (in sheep), and decreased capillary absorption (in rats). These renal and hemodynamic changes are also characteristic of the early (first 6 h) response to endotoxin. Therefore ANF should be considered as a potential mediator of renal and hemodynamic changes induced by sepsis. It is difficult to determine if ANF elevation is an epiphenomenon or a causative factor, because no antagonist of ANF is currently available.

Topics: Animals; Atrial Natriuretic Factor; Blood Pressure; Disease Models, Animal; Heart Rate; Potassium; Radioimmunoassay; Sheep; Sodium; Toxemia; Vascular Resistance