Left ventricular dysfunction and acute lung injury induced by continuous administration of endotoxin in sheep

Hiroshi Noda, Shinji Noshima, Hiroaki Nakazawa, Jörg Meyer, David N. Herndon, Heinz Redl, John Flynn, Lillian D. Traber, Daniel L. Traber

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17 Scopus citations

Abstract

Sixteen sheep were surgically prepared for chronic study. Seven days later, Escherichia coli endotoxin (10 ng/kg/min, lipopolysaccharide (LPS) 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 hypodynamic 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 end-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 pulmonary vascular resistance index (PVRI) were remarkably increased 1 h after 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). The early changes in cardiopulmonary function occurred concomitantly with an elevation in tumor necrosis factor (LPS 1221 ± 520; sham 0 ± 0 pg/ml) and thromboxane B2 (LPS 1382 ± 266; baseline 82 ± 20 pg/ml) in arterial blood. Following this first phase, the sheep presented a persistent hyperdynamic state characterized by a significant increase in Cl. The ESPDR continued to fall. By 24 h post-LPS the Cl 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 was maintained for the duration of the LPS infusion. On the other hand, the pulmonary vascular resistance had returned to near the baseline value by 16 h after the endotoxin infusion. PaO2 fell and pulmonary shunt fraction rose in the LPS group at 24 h (PaO2: LPS 85 ± 9; sham 115 ± 4 mmHg, shunt: LPS 0.28 ± 0.04; sham 0.09 ± 0.01). Lung lymph flow (LPS 39.1 ± 6.5; sham 8.1 ± 0.8 ml/h) and wet: dry ratio (LPS 5.54 ± 0.13; sham 4.89 ± 0.09) were increased in LPS group at 24 h post-LPS. In our model of hyperdynamic state of sepsis simulating the human condition there is an increased Cl despite a significant depression in myocardial contractility and acute lung injury.

Original languageEnglish (US)
Pages (from-to)291-298
Number of pages8
JournalShock
Volume1
Issue number4
DOIs
StatePublished - Apr 1994

ASJC Scopus subject areas

  • Emergency Medicine
  • Critical Care and Intensive Care Medicine

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    Noda, H., Noshima, S., Nakazawa, H., Meyer, J., Herndon, D. N., Redl, H., Flynn, J., Traber, L. D., & Traber, D. L. (1994). Left ventricular dysfunction and acute lung injury induced by continuous administration of endotoxin in sheep. Shock, 1(4), 291-298. https://doi.org/10.1097/00024382-199404000-00008