Development of pulmonary fibrosis after heart failure induced by elevated left atrial pressure.

BACKGROUND: Chronic heart failure (CHF) is a common and serious complication of patients with ischemic heart disease that may eventually lead to the development of pulmonary fibrosis. While other forms of pulmonary fibrosis have been studied extensively, little is known about the mechanisms that lead to heart failure associated with pulmonary fibrosis. The purpose of our study was to develop a rat pulmonary edema/fibrosis model induced by chronically elevated left atrial pressure (LAP), simulating CHF pathophysiology. METHODS: In adult rats, LAP was elevated by 15-20 mmHg through mechanical restriction of left ventricular diastolic filling with a maximum effect occurring at 7 days. Sham rats were surgically operated without LAP elevation. Lung tissues were analyzed for wet-to-dry ratio, hydroxyproline content, cellular invasion, and tissue integrity. Lung compliance and airway resistance served as pulmonary mechanical parameters. Hemodynamic parameters, including arterial pressure, heart rate, and cardiac output, were recorded in Sham and LAP elevated rats for 7 days. RESULTS: With increased LAP, pulmonary water content was significantly elevated accompanied by a decrease in lung compliance. Hydroxyproline markedly increased with chronic left atrial pressure elevation, suggesting fibrosis development. Simultaneously, heart failure induced a decrease in cardiac function. CONCLUSIONS: LAP elevation resulted in chronic pulmonary edema and tissue fibrosis formation associated with pulmonary dysfunction as measured by decreased dynamic lung compliance.