Abstract 88: Alterations in Pulmonary Vasoreactivity Following Lung Contusion in Rats
Lung contusion, a common complication of blunt chest trauma is an independent risk factor for ALI/ARDS. Using a recently described rat model for isolated bilateral lung contusion from blunt chest trauma (Anesth Analg 2005;101:1482), studies suggested an inconsistent correlation between the extent of inflammation and hypoxia. We set out to investigate the alteration in pulmonary arterial (PA) reactivity in lung contusion.
Methods: Lung contusion was induced in anesthetized spontaneously breathing adult male rats by dropping a hollow aluminum cylindrical weight (300 g) onto the chest with a protective shield placed on the precordium. Rats were allowed to recover and sacrificed at 4h and 24h (n=6 –9) and compared to uninjured controls. Third generation PA rings were dissected and placed in a bath with modified Krebs solution, connected to a transducer and bubbled with 21% O2+ 6% CO2. Some rings were pretreated with a non-specific NO synthase (NOS) inhibitor, L-nitro arginine (LNA 10−3 M). Rings were constricted with norepinephrine (NE) and relaxed with either a NOS agonist (A 23187) or NO donor (SNAP) at 10−6 M.
Results: Rats were hypoxic at 4h post-contusion (A-a gradient 337 ± 49 mmHg, mean ± SE) compared to controls (196 ± 29), but recovered 24h after contusion (217 ± 22). Pretreatment with LNA increased baseline tension significantly more in control PA compared to 4h or 24h post-contusion PA (130 ± 14, 112 ± 22 and 66 ± 16 g/g respectively). Constriction response to NE in the presence of LNA was significantly higher 4h after contusion compared to controls (671 ± 114 vs 392 ± 77 g/g). Relaxation to A23187 (73 ± 5 vs 33 ± 7%) and SNAP (88 ± 7 vs 45 ± 12%) were significantly impaired 24h after contusion compared to controls. Pretreatment with LNA improved relaxation to SNAP in PA isolated from contused lungs.
Conclusions: Hypoxemia and increased PA contractility are observed 4h after lung contusion in rats with recovery by 24h. Production of and response to NO are significantly diminished in PA following lung contusion.
Speculation: Uncoupling of NOS with reduced production of NO and increased production of superoxide may be observed in PA following lung contusion. Therapy with inhaled NO and antioxidants such as superoxide dismutase may alleviate hypoxemia following lung contusion.