This review explores the pathophysiology of gas exchange abnormalities arising consequent to either acute or chronic elevation of pulmonary venous pressures. The initial experimental studies of acute pulmonary edema outlined the sequence of events from lymphatic congestion with edema fluid to frank alveolar flooding and its resultant hypoxemia. Clinical studies of acute heart failure (HF) suggested that hypoxemia was associated only with the final stage of alveolar flooding. However, in patients with chronic heart failure and normal oxygenation, hypoxemia could be produced by the administration of potent pulmonary vasodilators, suggesting that hypoxic pulmonary vasoconstriction is an important reflex for these patients. Patients with chronic left HF commonly manifest a reduced diffusing capacity, an abnormality that appears to be a consequence of chronic elevation of left atrial pressure. That reduction in diffusing capacity does not appear to be primarily attributable to increases in lung water but is improved by any sustained treatment that improves overall cardiac function. Patients with heart failure may also manifest an abnormally elevated VE/VCO2 during exercise, and that exercise ventilation abnormality arises as a consequence of both alveolar hyperventilation and elevated physiologic dead space. That elevated exercise VE/VCO2 in an HF patient has proven to be a powerful predictor of an adverse outcome and hence it has received sustained attention in the HF literature. At least three of the classes of drugs used to treat HF will normalize the exercise VE/VCO2, suggesting that the excessive ventilation response may be linked to elevated sympathetic activity.
© 2011 American Physiological Society. Compr Physiol 1:621-634, 2011.