Background: During cardiac arrest use of an impedance threshold device (ITD) increases circulation and the chances for survival. The ITD has not been systematically evaluated during conventional CPR in a pediatric animal model. We hypothesized that the ITD increases blood flow to the brain by lowering intrathoracic pressure during the CPR decompression phase thus enhancing venous return to the right heart and forward flow with the subsequent compression and maintaining or lowering diastolic intracranial pressure (ICP) thus reducing resistance to forward flow. In this manner ITD use was hypothesized to mimic the ‘gasping reflex’ during CPR. Methods: In the first study 9 female propofol anesthetized piglets (10–12 kg) were subjected to 6 min of untreated ventricular fibrillation, 6 min of conventional CPR (ventilation rate 10 bpm), then 6 min of CPR with an active ITD (resistance of −10 cm H20). A second study was similar except that a sham ITD was used in 8 piglets. Results: After 2 min of active ITD treatment, decompression phase airway pressures (surrogate for intrathoracic pressure) (mmHg) decreased from −0.5 ± 0.2 to −2.6 ± 0.5 (mean ± SEM, p < 0.001) and common carotid blood flow (mL/min) increased by 65% (59.2 ± 16.7 to 91.1± 27.9, p = 0.02). In the sham group, airway pressures were unchanged and carotid blood flow decreased from 39 ± 2.5 to 38.8 ± 4.3 (p = 0.47). ICP decreased more rapidly in time and to a greater degree in 6/9 piglets when comparing ITD use to measurements preceding its application, contributing to an increase in cerebral perfusion (CePP) (mmHg) in 5/9 active ITD piglets, while in the sham group, CePPs remained the same or decreased in 8/8 piglets (p = 0.03). Coronary perfusion pressures (CPP) (mmHg) increased in 5/9 piglets after 2 min of the active ITD and remained the same or decreased in 8/8 piglets treated with the sham device (p = 0.03). Return of spontaneous circulation was achieved with a single shock in 4/9 active ITD piglets and 1/8 sham ITD piglets (p = 0.29). Conclusions: Use of an active ITD during CPR in piglets significantly increased carotid blood flow and CPPs. The ITD also lowered ICP during the decompression phase, similar to the mechanism of the ‘last gasp’, thereby reducing resistance to forward blood flow to the brain.