Low-dose vasopressin improves cardiopulmonary functions in sheep with combined burn and smoke inhalation injury

Background

Arginine vasopressin (AVP) is increasingly used for hemodynamic support in critically ill patients. However, the effects on reactive nitrogen species and pulmonary function are still not fully understood. We hypothesized that infusion of low-dose AVP improves cardiopulmonary performance by limiting nitrate/nitrite (NOx) and peroxynitrite (ONOO^-) formation.

Methods

Chronically instrumented sheep were randomly allocated to: healthy controls (sham), injured controls (40%, third-degree burn; 4 × 12 breaths of cotton smoke, <40°C), or an injured intervention group treated with a continuous AVP infusion (0.02 U/min) from 1 hour post injury to the remainder of the 24-hour period of study (n = 6 each/group). Physiologic variables and NOx plasma levels (chemiluminescence) were analyzed intermittently. Post mortem, lung tissue was harvested for the determination of the wet/dry weight ratio and airway obstruction. In addition, 3-nitrotyrosine concentrations (stable biomarker of ONOO^-) in lung and heart tissues were measured using immunohistochemistry and ELISAs. Data are expressed as the mean ± SEM. For statistical analysis a two-way ANOVA for repeated measurements with appropriate post-hoc comparisons (Student–Newman–Keuls) was performed.

Results

There were no differences between groups at baseline. All variables remained stable in sham animals throughout the entire experiment. Compared with injured controls, AVP reduced NOx plasma levels (24 hours: 9.5 ± 1.2 vs 4.5 ± 0.9 μmol/l), improved PaO₂/FiO₂ ratio (24 hours: 214 ± 20 vs 431 ± 38, each P < 0.001) and decreased the degree of pulmonary edema and airway obstruction. In addition, AVP improved myocardial contractility, as indexed by increased left ventricular stroke work index (24 hours: 52 ± 7 vs 87 ± 10 g/m/m²). Compared with injured controls, AVP prevented the increase in 3-nitrotyrosine concentrations (lung: 43 ± 4 vs 32 ± 3 nM; heart: 37 ± 5 vs 22 ± 3 nM; P < 0.01 each).

Conclusion

This study suggests that low-dose AVP infusion may be a rational approach to attenuate cardiopulmonary dysfunctions resulting from combined burn and smoke inhalation injury. The effects of AVP in this model may be related to inhibition of the cytotoxic ONOO^-.