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Biphasic positive airway pressure (BIPAP) allows unrestricted spontaneous breathing throughout mechanical ventilation. Effects of spontaneous breathing during BIPAP on pulmonary gas exchange were studied on a randomized basis in 12 dogs with oleic acid-induced lung injury using the multiple inert gas elimination technique. Spontaneous breathing during BIPAP, accounting for 10% of minute ventilation (VE), increased PaO2 from 61 +/- 2 to 78 +/- 3 mm Hg (mean +/- SE) (p < 0.01), cardiac output from 4.2 +/- 0.3 to 4.6 +/- 0.3 L/min (p < 0.05), and oxygen delivery from 537 +/- 51 to 716 +/- 58 ml/kg/min (p < 0.05), whereas oxygen consumption and total VE remained unchanged. Improved pulmonary gas exchange caused by better ventilation/perfusion (VA/Q) matching was indicated by a 17 +/- 3% decrease (p < 0.01) in blood flow to shunt units (VA/Q < 0.005), a 15 +/- 3% increase (p < 0.05) in perfusion of normal VA/Q units (0.1 < VA/Q < 10), and a 6 +/- 3% reduction in ventilation of dead space (VA/Q > 100) areas (p < 0.05). Spontaneous breaths superimposed on mechanical ventilation may convert shunt VA/Q units to normal by increased ventilation of poorly or nonventilated units and/or increase blood flow to previously minimal or nonperfused areas.