Anesthetized and critically ill patients often have significant alterations in gas exchange. Regional matching of ventilation (V) and perfusion (Q) is the key physiological event that ensures optimal gas exchange in the lungs, with a VQ ratio = 1 defining an ideal unit. While VQ is closely matched globally, regional imbalances favoring V or Q are observed in different lung regions. Given this heterogeneous distribution of VQ ratios, global estimates of VQ matching may not accurately reflect what happens in certain lung regions. Common clinical scenarios such as acute hemorrhage or the infusion of vasoactive drugs can affect the global VQ relationship, but its regional effects are largely unknown. The overarching aim of this proposal is to understand the effects of vasoactive drug infusion commonly used in the clinical setting and the effects of hemorrhage and blood volume replacement on the topographic regional distribution of VQ ratios in healthy anesthetized lungs. Our first specific aim is to evaluate the regional distribution of VQ ratios in the lungs of healthy anesthetized pigs in dorsal recumbency. This aim will serve as the control against which we will compare the effects of acute hemorrhage and the infusion of different doses of vasoactive drugs on the regional distribution of VQ ratios, which is our second specific aim. Finally, we aim to compare the different information about VQ mismatch when evaluated by global versus regional estimates. We have recently refined a method to describe the distribution of regional VQ ratios in anesthetized horses using thoracic electric impedance tomography (EIT). With this methodology, we expect to generate high-quality maps of regional VQ ratio distributions. Eight adult, healthy pigs will be anesthetized and mechanically ventilated. A custom-made belt with 32 electrodes positioned in a 2 x 16 electrode arrangement will be placed around the thorax. This special electrode arrangement will allow for 3D reconstruction of EIT data, giving information about the ventrodorsal, laterolateral and caudocranial distribution of VQ ratios. Pigs will be instrumented with a central venous catheter and pulmonary and femoral artery catheters. Five phases will be studied in fixed order: 1) baseline; 2) phenylephrine infusion; 3) dobutamine infusion; 4) hemorrhage; 5) blood volume replacement. During each phase, arterial and mixed venous blood gases will be measured and volumetric capnography will be recorded. For EIT measurements, thoracic impedance images will be sampled at a high rate and recorded for 2 minutes while the animal is ventilated. In order to evaluate pulmonary blood flow, another set of impedance recordings will be taken while briefly stopping ventilation to induce apnea and a volume of 0.2 ml/kg of hypertonic saline (10%) will be injected rapidly through a central line. Mathematical models will be used to reconstruct the EIT images and to create the regional maps of VQ ratio distributions. Global indices of VQ mismatch will be calculated using volumetric capnography and arterial and mixed venous samples. Data will be compared using linear mixed models with pigs as random effect and treatment as fixed effect. We expect to generate high-quality and novel data that will allow clinicians to better understand the effects of common clinical events in the regional distribution of VQ ratios and its impact in overall gas exchange. This knowledge will be applied in future related studies evaluating the ideal vasoactive drugs in presence of lung pathology or during advanced procedures such as one-lung ventilation.