Abstract
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 language | English (US) |
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Pages (from-to) | H1616-H1625 |
Journal | American Journal of Physiology - Heart and Circulatory Physiology |
Volume | 285 |
Issue number | 4 54-4 |
DOIs | |
State | Published - Oct 1 2003 |
Keywords
- 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)