Time-dependent cardiovascular and inflammatory changes in acute endotoxemia

Kingsley Yin, Carl E. Hock, Maria Tahamont, Patrick Y.K. Wong

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

The pathophysiology of experimental acute endotoxemia is a complex process involving both cardiovascular dysfunction and an inflammatory response. We have examined the correlation in hemodynamic changes and the pulmonary inflammatory response after lipopolysaccharide (LPS) administration with respect to time. Importantly, we have measured the lung and plasma levels of nitric oxide (NO) over time, as well as rapid generation of lung superoxide after LPS administration. In anesthetized rats given a bolus injection of LPS (10 mg/kg intravenously, from Salmonella enteritidis), mean arterial blood pressure dropped by 63-70% within 15 min, and cardiac output fell by 57-63% within 20 min compared with saline controls. Mean arterial blood pressure recovered slightly but was still 51, 30, and 25% less than that of saline controls 45, 105, and 165 min after LPS administration, respectively. Cardiac output remained depressed throughout the experimental period and was 35% lower than in saline controls 165 min after LPS treatment. There was a small increase in plasma nitrite/nitrate as an index of plasma NO production after 45 min and a 10-fold increase 165 min after LPS addition compared with controls, strongly suggesting that NO mediates the hypotension that occurs 165 min after LPS administration. Lung NO production increased twofold 105 min after LPS administration and remained higher than in saline controls. Histological sections showed that there was fluid accumulation and alveolar collapse in the lung 45 min after LPS, whereas after 165 min, there was extensive tissue damage and increased leukocyte accumulation compared with controls. These results suggest that there was no correlation between early (1 h) tissue damage and NO production. We found an increase in lung superoxide generation 15 min after injection of LPS that coincided with the alterations in cardiovascular function. These results suggest that early lung tissue damage and/or hemodynamic changes may be due to superoxide generation from the lung.

Original languageEnglish (US)
Pages (from-to)434-442
Number of pages9
JournalShock
Volume9
Issue number6
DOIs
StatePublished - Jun 1998

All Science Journal Classification (ASJC) codes

  • Emergency Medicine
  • Critical Care and Intensive Care Medicine

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