OBJECTIVE Infrarenal aortic cross-clamping (ACC) induces hemodynamic disturbances that may affect respiratory-induced variations in stroke volume and, therefore, affect the ability of dynamic parameters such as pulse-pressure variation (PPV) to predict fluid responsiveness. Since this issue has not been investigated yet to authors' knowledge, the hypothesis was tested that ACC may change PPV and impair its ability to predict fluid responsiveness. METHODS Prospective laboratory experiment. METHODS A university research laboratory. METHODS Nineteen anesthetized and mechanically ventilated pigs. METHODS Two courses of volume expansion were performed using 500 mL of saline before and during ACC. Animals were monitored using a systemic arterial catheter, and a pulmonary arterial catheter (stroke volume, central venous pressure, pulmonary arterial occlusion pressure). Animals were defined as responders to volume expansion if stroke volume increased ≥ 15%. RESULTS Before ACC, 13 animals were responders. Fluid responsiveness was predicted by a PPV ≥ 14% with a sensitivity of 77% (95% CI = 46%-95%) and a specificity of 83% (95% CI = 36%-97%). The area under the receiver operating characteristic curve was 0.90(95% CI = 0.67-0.99) and was higher than those generated for central venous pressure and pulmonary arterial occlusion pressure. ACC induced an increase in PPV (p<0.0005). During ACC, 8 animals were responders. An 18% PPV threshold discriminated between responders and non-responders to volume expansion, with a sensitivity of 87% (95% CI = 47%-98%) and a specificity of 54% (95% CI = 23%-83%). The area under the receiver operating characteristic curve was 0.72 (95% CI = 0.47-0.90) and was not different from those generated for central venous pressure and pulmonary arterial occlusion pressure. CONCLUSIONS ACC induced a significant increase in PPV and reduced its ability to predict fluid responsiveness.