Abstract: Slide Presentations |

Increased alveolar adenosine levels downregulate pulmonary edema clearance during hyperoxic acute lung injury FREE TO VIEW

Gokhan M. Mutlu, MD*; Janice M. Martino, BS; Rajesh Balagani, DO; Vidas Dumasius, BS; Sargon J. Albazi, PhD; Phillip Factor, DO
Author and Funding Information

Northwestern University, Chicago, IL


Chest. 2004;126(4_MeetingAbstracts):719S. doi:10.1378/chest.126.4_MeetingAbstracts.719S
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PURPOSE:  Alveolar active Na+ transport is impaired during some types of acute lung injury. Pulmonary edema increases alveolar active Na+ transport via a beta-adrenergic receptor (betaAR) dependent pathway which increases cellular ATP consumption and cAMP production, which provide substrate for adenosine production. Extracellular adenosine may regulate cellular energy consumption by inhibiting adenylyl cyclase activity. We hypothesized that adenosine levels are elevated during lung injury and may be contribute to downregulation of alveolar active Na+ transport.

METHODS:  Adenosine levels were measured using an HPLC method in blood and bronchoalveolar lavage fluid (BALF) from mice exposed to hyperoxia (100% oxygen, 66 hrs) or treated with procaterol (a beta2-agonist, 10–6 M). These mice were compared to untreated room air controls. To test if adenosine affects active Na+ transport, alveolar fluid clearance (AFC) was measured with adenosine or the adenosine receptor type 1 (A1R) agonist, cyclopentyladenosine (CPA) using a live, mechanically ventilated lung model.

RESULTS:  BALF adenosine levels were increased >100% in hyperoxic animals compared to normal animals (0.66±0.05 vs. 1.42±0.82 micM). Serum adenosine levels were decreased in hyperoxic mice (8.1±3.9 vs. 53.2±13.4 micM). Procaterol increased both serum and BALF adenosine levels by 100%. Intratracheal adenosine at concentrations greater than 10-8M reduced AFC up to 42%. CPA reduced AFC by up to 80% suggesting that adenosine’s inhibitory effects on AFC may be mediated via A1R.

CONCLUSION:  Lung adenosine levels are elevated during hyperoxic acute lung injury and following beta-agonist treatment and are sufficient to inhibit alveolar active Na+ transport, perhaps via an A1R dependent pathway. We speculate that lung adenosine levels rise as a consequence of increased catecholamine driven alveolar Na+ transport. Accordingly, adenosine represents a negative feedback mechanism that allows alveolar epithelial cells to regulate betaAR mediated increases in active Na+ transport and energy consumption. These new findings represent the first report of a mechanism by which the alveolar epithelium can regulate energy consumption.

CLINICAL IMPLICATIONS:  Pharmacologic inhibition of the A1R may be a new approach in treating pulmonary edema.

DISCLOSURE:  G.M. Mutlu, None.

Monday, October 25, 2004

2:30 PM- 4:00 PM




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