C. M. Doerschuk

Evaluation of Reexpansion Pulmonary Edema Following Unilateral Pneumothorax in Rabbits and the Effect of Superoxide Dismutase

We investigated the lung injury that occurs following reexpansion of a unilateral pneumothorax and determined the effect of superoxide dismutase (SOD) infused immediately prior to reexpansion on this injury. After 7 days of at least 80% right pneumothorax, rabbits received intravenous infusions of either SOD (n = 7), heat-inactivated SOD (n = 1), or vehicle (n = 7) immediately before lung reexpansion. Lung injury was assessed by measuring the systemic white cell counts, pulmonary blood volumes, extravascular albumin, extravascular lung water, wet/dry weight ratios, and histology 2 h after reexpansion. The reexpanded lung showed increased extravascular albumin, extravascular lung water and wet/dry weight ratios with decreased blood volumes compared to the uninjured lung. SOD delayed the onset of leukopenia and neutropenia at 3 and 7 min after reexpansion, but the white cell counts had decreased to the same level in both groups by 30 min. SOD had no effect on the degree of injury after 2 h. While a single bolus of SOD given immediately before reexpansion delayed the onset of this injury, it did not affect the injury that subsequently developed in the lung.

Role of Protein Synthesis and CD 11 /CD 18 Adhesion Complex in Neutrophil Emigration into the Lung

The mechanism of neutrophil (PMN) emigration into the lung may be stimulus-dependent. This study examined PMN emigration in the lung induced by intratracheal instillation of lipopolysaccharide (LPS), Streptococcus pneumoniae (S. pneu) organisms, supernatant from S. pneu incubated with alveolar macrophages (AM phi), Escherichia coli (E. coli) organisms, or phorbol myristate acetate (PMA). Rabbits were pretreated with either the CD18 monoclonal antibody (MAb) 60.3, the protein synthesis inhibitor cycloheximide (Cx), or, in one case, both. Animals were then given one of the above stimuli to elicit PMN emigration. Four hours after the stimulus was instilled, animals were killed and total and differential cell counts were performed on bronchoalveolar lavage (BAL) fluid. PMN emigration in response to PMA was virtually abolished by MAb 60.3, but was not significantly inhibited by Cx. Emigration induced by LPS was inhibited by 80% by either MAb 60.3 or Cx, and greater than 94% when MAb 60.3 and Cx were given simultaneously. Emigration in response to E. coli organisms was 80% inhibited by MAb 60.3. Emigration induced by S. pneu was approximately 50% inhibited by MAb 60.3, but was greater than 90% blocked by Cx. The MAb 60.3 had approximately the same effect on PMN emigration toward the supernatant from co-incubation of AM phi with S. pneu as it did toward live S. pneu. It is concluded that the mechanism of PMN emigration into the lung is stimulus-dependent. The CD18-dependent mechanism is responsible for the majority of the emigration in response to PMA, E. coli LPS, and E. coli organisms. S. pneu and supernatant from S. pneu + AM phi produce a CD18-independent pathway. These data suggest the requirement for de novo protein synthesis for PMN emigration in response to LPS and S. pneu, but not for PMA-induced emigration.

Changes measured in arterial blood following a single breath of cigarette smoke in rabbits

This paper describes a method for monitoring short term changes in arterial blood in rabbits in response to a single breath of cigarette smoke. The method was developed to investigate the observation that neutrophil transit times through the lung are extended during acute exposures to cigarette smoke (1). In this model, we sought to monitor the time course of appearance of diffusible gas from smoke to the blood stream, the appearance of lipid peroxidation products and the activation of neutrophils. New Zealand white rabbits were anesthetized and fitted with a tracheostomy tube and an aortic catheter. Smoke was collected in a syringe from a non-filtered cigarette and injected immediately via the tracheostomy tube. Blood samples were collected at 1 second intervals. Carboxyhemoglobin levels increased 108% over pre-smoke levels, peaking at 5-7 seconds after the start of smoke exposure. Serum conjugated dienes, as measured by change in absorbance of lipid extracts at 234 nm, increased 40%, peaking at 10-11 seconds. Thiobarbituric acid (TBA) reactive material exhibited a variable response, with a statistically insignificant maximum at 12 seconds. Serum myeloperoxidase activity was not affected by smoke inhalation. This method provides a model for studying the acute effects of smoke inhalation and provides some evidence for oxidant stress following a single breath of cigarette smoke.