Numerous approaches to the provision of mechanical ventilation during acute lung injury are currently available. Of these, pressure control inverse ratio ventilation has been considered superior to volume control ventilation with PEEP with respect to improving gas exchange and minimizing cardiovascular compromise. However, no study systematically compares volume-controlled (VC) and pressure-controlled (PC) ventilation while maintaining mean airway pressure (MAP) constant at varying I/E ratios. We studied the effect of VC and PC with PEEP at normal (1:2) and inverse I/E ratios (2:1 and 4:1) on gas exchange, lung mechanics, and hemodynamics in a sheep lung injury model. Severe lung injury was induced in 12 sheep with bilateral lung lavages using normal saline; prelavage PO2 230 +/- 50 mm Hg, PEEP 5 cm H2O and postlavage, pretreatment PO2 70 +/- 20 mm Hg, PEEP 10 cm H2O, both at FIO2 0.50. MAP was kept constant throughout the study at 25 +/- 2 cm H2O while ventilating all animals with a VT of 10 ml/kg and a rate of 20/min by randomized application of VC and PC with I/E ratios of 1:2, 2:1, and 4:1. Despite liberal fluid administration, all ventilatory modes depressed cardiac output compared with preinjury values. However, gas exchange and hemodynamics did not differ among ventilation modes or I/E ratios.(ABSTRACT TRUNCATED AT 250 WORDS)