Respiratory Physiology & Neurobiology 139 (2004) 167–177 Pulmonary mechanics and lung histology in acute lung injury induced by Bothrops jararaca venom Keyla S.O. Silveira a , Nicolau T. Boechem b , Suliane M. do Nascimento b , Yugo L.B. Murakami c , Ana P.B. Barboza a , Paulo A. Melo c , Paulo Castro d , Vera L.G. de Moraes d , Patricia R.M. Rocco b , Walter A. Zin a,∗ a Laboratory of Respiration Physiology, Carlos Chagas Filho Biophysics Institute, Ilha do Fundão, 21949-900 Rio de Janeiro, RJ, Brazil b Laboratory of Pulmonary Investigation, Carlos Chagas Filho Biophysics Institute, Ilha do Fundão, 21949-900 Rio de Janeiro, RJ, Brazil c Department of Basic and Clinical Pharmacology, Federal University of Rio de Janeiro, Ilha do Fundão, 21949-900 Rio de Janeiro, RJ, Brazil d Department of Medical Biochemistry, Federal University of Rio de Janeiro, Ilha do Fundão, 21949-900 Rio de Janeiro, RJ, Brazil Accepted 8 October 2003 Abstract Pulmonary mechanics [static (Est) and dynamic (Edyn) elastances, resistive (P1) and viscoelastic pressures (P2)], histology, and bronchoalveolar lavage fluid (BALF) from BALB/c mice were analysed 1, 24, 48 and 72 h after intravenous injection of saline or Bothrops jararaca crude venom [0.3 (V0.3) or 1 (V1) g·g -1 ]. Est, Edyn, and P2 increased at 1 h in both V groups, being significantly higher in V1 than in V0.3, decreasing progressively, reaching control values at 48 h in V0.3, but remaining altered in V1 at 72 h. P1 augmented in V1 at 1 h, returning to normal at 72 h. Histological changes in V0.3 group included interstitial oedema, alveolar collapse, and increased cellularity, which returned to normal at 48 h. These changes were more intense in V1 group, with alveolar oedema and haemorrhage. BALF showed time-dependent neutrophil influx in V0.3. In conclusion, venom led to time- and dose-dependent pulmonary mechanical changes, together with moderate inflammation in V0.3 and acute lung injury in V1. © 2003 Elsevier B.V. All rights reserved. Keywords: Bronchi, broncho-alveolar lavage; Disease, acute lung injury, inflammation; Mammals, mouse; Mechanics of breathing, elastance, pressure; Pressure, resistive, viscoelastic; Venom, Bothrops jararaca 1. Introduction Snakes of the genus Bothrops (Lanceheads, family Viperidae) are responsible for higher human mor- bidity in the new world than any other group of ∗ Corresponding author. Tel.: +55-21-2564-1578; fax: +55-21-2280-8193. venomous snakes. The most important species are B. asper in Central America and B. jararaca and B. atrox in South America (Camey et al., 2002). In Brazil, Bothrops species are responsible for 90% of all recorded snakebites (20,000/year), with lethality around 0.31%. Envenoming by B. jararaca is char- acterised by systemic (renal and pulmonary failure, shock, generalised bleeding and coagulopathy) and 1569-9048/$ – see front matter © 2003 Elsevier B.V. All rights reserved. doi:10.1016/j.resp.2003.10.002