Modulation of endotoxin-induced cardiopulmonary dysfunction by S-nitroso-albumin

Tracy Gluckman, Jeffrey E. Grossman, John D. Folts, Kris T. Kruse-Elliott

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Nitric oxide (NO) is an endogenous vasodilator and modulator of inflammation. During endotoxemia, the beneficial effects of NO are overwhelmed by the inflammatory cascade, resulting in a functional depletion of NO. S-nitroso-albumin (S-NO-alb) exists as a novel and highly stable NO thiol complex that slowly releases NO into the vascular micro-environment. Using a porcine model, we examined the ability of intravenous S-NO-alb to modulate cardiopulmonary dysfunction characteristic of endotoxemia. Pigs were anesthetized, instrumented for standard cardiopulmonary function measurements, and randomly assigned to receive: (i) albumin + saline; (ii) albumin + LPS; or (iii) S-NO-alb + LPS. Cardiopulmonary parameters were evaluated every 30 min and ex vivo phorbol myristate acetate (PMA)-stimulated superoxide release was serially determined as a marker of in vivo neutrophil priming. Lung myeloperoxidase (MPO) activity was measured as a marker of neutrophil migration into the lung. LPS-induced cardiopulmonary dysfunction was characterized by a sustained elevation in mean pulmonary arterial pressure, pulmonary vascular resistance, and peak intratracheal pressure, as well as a reduction in cardiac index, stroke volume index and PaO2 over 6 h. Pretreatment with S-NO-alb attenuated LPS-induced cardiopulmonary dysfunction without adversely affecting systemic hemodynamics. Moreover, S-NO-alb blunted the LPS-induced hypoxemic response and reduced neutrophil activation. S-NO-alb did not, however, attenuate LPS-induced increases in lung MPO. Our results suggest that S-NO-alb can selectively modulate endotoxin-induced pulmonary dysfunction, attenuate neutrophil priming and block the early mortality (40%) in this model.

Original languageEnglish (US)
Pages (from-to)17-26
Number of pages10
JournalJournal of Endotoxin Research
Volume8
Issue number1
DOIs
StatePublished - 2002
Externally publishedYes

Fingerprint

Endotoxins
Modulation
Nitric Oxide
Lung
Neutrophils
Endotoxemia
Peroxidase
Albumins
Swine
Neutrophil Activation
Hemodynamics
Tetradecanoylphorbol Acetate
S-nitrosoalbumin
Vasodilator Agents
Sulfhydryl Compounds
Superoxides
Vascular Resistance
Stroke Volume
Modulators
Blood Vessels

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Toxicology

Cite this

Modulation of endotoxin-induced cardiopulmonary dysfunction by S-nitroso-albumin. / Gluckman, Tracy; Grossman, Jeffrey E.; Folts, John D.; Kruse-Elliott, Kris T.

In: Journal of Endotoxin Research, Vol. 8, No. 1, 2002, p. 17-26.

Research output: Contribution to journalArticle

Gluckman, Tracy ; Grossman, Jeffrey E. ; Folts, John D. ; Kruse-Elliott, Kris T. / Modulation of endotoxin-induced cardiopulmonary dysfunction by S-nitroso-albumin. In: Journal of Endotoxin Research. 2002 ; Vol. 8, No. 1. pp. 17-26.
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