We have previously shown improved cardiac output (QT) with external continuous negative-pressure ventilation (CNPV) compared with continuous positive-pressure ventilation (CPPV) in dogs with low pressure pulmonary edema (1). The current study was done to determine if this effect was reversed in high pressure pulmonary edema. Seven supine, anesthetized dogs were fluid-loaded and treated with disopyramide (3.5 to 7.0 mg/kg) and propranolol (0.25 to 1.5 mg/kg). This produced a mean pulmonary wedge pressure (Ppaw) of 21.0 mm Hg on intermittent positive-pressure ventilation (IPPV). CPPV and CNPV were then alternated at 30-min intervals. Ventilators were matched for oxygen concentration, frequency, tidal volume (VT), and the increment in FRC (delta FRC) produced by a given positive (PEEP) or negative (NEEP) end-expiratory pressure. During 20 cm H2O of PEEP, QT values were significantly depressed from IPPV control values (2.13 +/- 0.2 versus 1.27 +/- 0.2 L/min, p less than 0.05) but not during CNPV with equivalent NEEP (1.66 +/- 0.2 L/min). Although arterial oxygen saturations were similar, mixed venous oxygen saturations were depressed by CPPV with PEEP of 15 and 20 cm H2O (67.9 +/- 3.8% during IPPV versus 54.1 +/- 4.9 and 51.9 +/- 5.8%, respectively, p less than 0.05 in both instances) but not during equivalent CNPV (59.9 +/- 4.3 and 58.7 +/- 4.5%). Despite potentially increased left ventricular afterload, external negative chest wall ventilation with NEEP does not appear to significantly depress QT compared with CPPV even when Ppaw is high and myocardial contractility is impaired.