BACKGROUND Both pulse pressure variation and stroke volume variation during intermittent positive-pressure ventilation predict preload responsiveness. However, because ventilatory and cardiac frequencies are not the same, increasing the number of breaths sampled may increase calculated pulse pressure variation and stroke volume variation because larger (max) and smaller (min) pulse pressure and stroke volume may occur. Tidal volume and contractility may also alter pulse pressure variation and stroke volume variation. We hypothesized that the magnitude of pulse pressure variation would increase with sampling duration, and that both tidal volume and contractility would independently alter pulse pressure variation and stroke volume variation. METHODS In seven pentobarbital-anesthetized intact dogs arterial and left ventricular pressure (Millar) and left ventricular volume (Leycom) were measured over 8 intermittent positive-pressure ventilation breaths at tidal volume of 5, 10, 15, and 20 mL/kg (f = 20/min, 40% inspiratory time) under baseline, esmolol (2 mg/min), dobutamine infusions (5 microg/kg/min) and following volume loading (500 mL NaCl). Stroke volume variation was calculated using pulse contour method (PiCCO, Pulsion Medical Systems, Munich, Germany) averaged over 12 secs. Pulse pressure variation was calculated as 100 x (PPmax - PPmin)/PPmean and calculated over 1, 2, 3, 4, 5, 6, 7, or 8 breaths. RESULTS Pulse pressure variation increased progressively with increasing sampling duration up to but not exceeding five breaths. The effect on sampling duration was increased by greater tidal volume. Esmolol infusion decreased both pulse pressure variation and stroke volume variation as compared with baseline (p < 0.05) at all tidal volume levels. However, dobutamine did not alter either pulse pressure variation or stroke volume variation. CONCLUSIONS Sampling duration, tidal volume, and beta-adrenergic blockade differentially alters pulse pressure variation and stroke volume variation during intermittent positive-pressure ventilation. Thus, separate validation is required to define threshold pulse pressure variation and stroke volume variation values used to drive resuscitation algorithms.