LEFT-VENTRICULAR DYSFUNCTION AND ACUTE LUNG INJURY-INDUCED BY CONTINUOUS ADMINISTRATION OF ENDOTOXIN IN SHEEP

Sixteen sheep were surgically prepared for chronic study. Seven days l ater, Escherichia coli endotoxin (10 ng/kg/min, lipopolysaccharide (LP S) group, n = 10) or an equivalent amount of 0.9% NaCl (Control group n = 6) was administered. Between 1 and 8 h post-LPS, there was a hypod ynamic state with low cardiac index (CI, LPS 5.0 +/- 0.2; sham 6.3 +/- 0.4 liters/min/m2 at 4 h). During this period, the left ventricular e nd-systolic pressure-diameter relationship (ESPDR), a sensitive index of myocardial contractility, was also lower (LPS 10.4 +/- 1.2; sham 17 .2 +/- 0.8 mmHg/mm). Mean pulmonary arterial pressure (PAP) and pulmon ary vascular resistance index (PVRI) were remarkably increased 1 h aft er the administration of LPS (PAP: LPS 37.5 +/- 1.9; sham 21.8 +/- 0.9 mmHg, PVRI: LPS 600 +/- 58; sham 158 +/- 23 dynes . s . cm-5. m2). Th e early changes in cardiopulmonary function occurred concomitantly wit h an elevation in tumor necrosis factor (LPS 1221 +/- 520; sham 0 +/- 0 pg/ml) and thromboxane B2 (LPS 1382 +/- 266; baseline 82 +/- 20 pg/m l) in arterial blood. Following this first phase, the sheep presented a persistent hyperdynamic state characterized by a significant increas e in CI. The ESPDR continued to fall. By 24 h post-LPS the CI was 10.1 +/- 0.5 liters/min/m2 (sham, 6.3 +/- 0.3) but the ESPDR had fallen to 8.2 +/- 2.3 mmHg/mm (sham 16.0 +/- 3.0). The pulmonary hypertension w as maintained for the duration of the LPS infusion. On the other hand, the pulmonary vascular resistance had returned to near the baseline v alue by 16 h after the endotoxin infusion. PaO2 fell and pulmonary shu nt fraction rose in the LPS group at 24 h (PaO2: LPS 85 +/- 9; sham 11 5 +/- 4 mmHg, shunt: LPS 0.28 +/- 0.04; sham 0.09 +/- 0.01). Lung lymp h flow (LPS 39.1 +/- 6.5; sham 8.1 +/- 0.8 ml/h) and wet: dry ratio (L PS 5.54 +/- 0.13; sham 4.89 +/- 0.09) were increased in LPS group at 2 4 h post-LPS. In our model of hyperdynamic state of sepsis simulating the human condition there is an increased CI despite a significant dep ression in myocardial contractility and acute lung injury.