Prolonged Alveolocapillary Barrier Damage After Acute Cardiogenic Pulmonary Edema

Objectives: To determine whether acute cardiogenic pulmonary edema is associated with damage to the alveolocapillary barrier, as evidenced by increased leakage of surfactant specific proteins into the circulation, to document the duration of alveolocapillary barrier damage in this setting, and to explore the role of pulmonary parenchymal inflammation by determining if circulating tumor necrosis factor-alpha is increased after acute cardiogenic pulmonary edema.

Design: Prospective, observational study.

Setting: Critical care, cardiac intensive care, and cardiology wards of a tertiary-care university teaching hospital.

Patients: A total of 28 patients presenting with acute cardiogenic pulmonary edema and 13 age-matched normal volunteers.

Interventions: Circulating surfactant protein-A and -B and tumor necrosis factor-alpha were measured on days 0 (presentation), 1, 3, 7, and 14. Clinical markers of pulmonary edema were documented at the same times.

Measurements And Main Results: Surfactant protein-A and -B were elevated on day 0 compared with controls (367 +/- 17 ng/mL vs. 303 +/- 17 and 3821 +/- 266 ng/mL vs. 2747 +/- 157 [mean +/- sem], p <.05), and although clinical, hemodynamic and radiographic variables improved rapidly (p <.001), surfactant protein-A and -B rose further until day 3 (437 +/- 22, p <.001, 4642 +/- 353, p <.01). Tumor necrosis factor-alpha was elevated at presentation (p <.05), doubled by day 1 (6.98 +/- 1.36 pg/mL, p <.05), remained elevated on day 3 (5.72 +/- 0.96 pg/mL, p <.05), and peak levels were related to chest radiograph extravascular lung water score (r(p) = 0.64, p =.003).

Conclusions: Although the initial increase in plasma surfactant protein-A and -B may represent hydrostatic stress failure of the alveolocapillary barrier, the prolonged elevation, when hemodynamic abnormalities have resolved, and the delayed elevation of tumor necrosis factor-alpha are consistent with pulmonary parenchymal inflammation, which may further damage the alveolocapillary barrier. This prolonged physiologic defect at the alveolocapillary barrier after acute cardiogenic pulmonary edema may partly account for the vulnerability of these patients to recurrent pulmonary fluid accumulation.