Molecular and pharmacological approaches to inhibiting nitric oxide after burn trauma

Jean White, Deborah L. Carlson, Marita Thompson, David L. Maass, Billy Sanders, Brett Giroir, Jureta W. Horton

Research output: Contribution to journalArticle

9 Scopus citations


Whereas controversial, several studies have suggested that nitric oxide (NO) alters cardiac contractility via cGMP, peroxynitrite, or poly(ADP ribose) synthetase (PARS) activation. This study determined whether burn-related upregulation of myocardial inducible NO synthase (iNOS) and NO generation contributes to burn-mediated cardiac contractile dysfunction. Mice homozygous null for the iNOS gene (iNOS knockouts) were obtained from Jackson Laboratory. iNOS knockouts (KO) as well as wild-type mice were given a cutaneous burn over 40% of the total body surface area by the application of brass probes (1 × 2 × 0.3 cm) heated to 100°C to the animals' sides and back for 5 s (iNOS/KO burn and wild-type burn). Additional groups of iNOS KO and wild-type mice served as appropriate sham burn groups (iNOS/KO sham and wild-type sham). Cardiac function was assessed 24 h postburn by perfusing hearts (n = 7-10 mice/group). Burn trauma in wild-type mice impaired cardiac function as indicated by the lower left ventricular pressure (LVP, 67 ± 2 mmHg) compared with that measured in wild-type shams (94 ± 2 mmHg, P < 0.001), a lower rate of LVP rise (+dP/dtmax, 1,620 ± 94 vs. 2, 240 ± 58 mmHg/s, P < 0.001), and a lower rate of LVP fall (-dP/dtmax, 1,200 ± 84 vs. 1,800 ± 42 mmHg/s, P < 0.001). Ventricular function curves confirmed significant contractile dysfunction after burn trauma in wild-type mice. Burn trauma in iNOS KO mice produced fewer cardiac derangements compared with those observed in wild-type burns (LVP: 78 ± 5 mmHg; +dP/dt: 1,889 ± 160 mmHg/s; -dP/dt: 1, 480 ± 154 mmHg/s). The use of a pharmacological approach to inhibit iNOS (aminoguanidine, given ip) in additional wild-type shams and burns confirmed the iNOS KO data. Whereas the absence of iNOS attenuated burn-mediated cardiac contractile dysfunction, these experiments did not determine the contribution of cardiac-derived NO versus NO generated by immune cells. However, our data indicate a role for NO in cardiac dysfunction after major trauma.

Original languageEnglish (US)
Pages (from-to)H1616-H1625
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Issue number4 54-4
StatePublished - Oct 1 2003


  • Cardiomyocyte secretion of nitric oxide
  • Inducible nitric oxide
  • Langendorff perfused hearts
  • Left ventricular function
  • Mouse model of burn trauma

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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  • Cite this

    White, J., Carlson, D. L., Thompson, M., Maass, D. L., Sanders, B., Giroir, B., & Horton, J. W. (2003). Molecular and pharmacological approaches to inhibiting nitric oxide after burn trauma. American Journal of Physiology - Heart and Circulatory Physiology, 285(4 54-4), H1616-H1625.