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Introduction: Cells under acute controlled ischemia initiate complex physiological adaptations to be able to better tolerate further hypoxic events. This phenomenon, called ischemic preconditioning, has been well described in myocardial cells, but can also occur in other tissues. We evaluated the potential therapeutic role of ischemic pre- and post-conditioning in experimental sepsis. Methods: We studied 16 sheep (25-35 Kg) monitored invasively and treated with volume controlled mechanical ventilation under anesthesia with midazolam, ketamine and morphine. We induced abdominal sepsis by injecting autologous feces into the peritoneal cavity and followed animals until death or for a maximum of 30 hours. Animals were randomly allocated to undergo ischemic preconditioning followed by intermittent post-conditioning (CONDITIONING) or not (CONTROL). Controlled ischemic episodes of the lower extremities and pelvis were obtained by inflating an intravascular balloon in the aortic bifurcation. We performed 4 cycles of 2 min ischemia (4 min apart) before sepsis induction and thereafter 1 inflation every 4 hours until death. We calculated the time taken to develop diuresis of <0.4 ml/Kg/hour (KIDNEYTIME), a lactate >2 mmol/L (LACTIME), a systemic mean arterial pressure <60 mmHg (HYPOTENSIONTIME), and the time to death (DEATHTIME), all expressed in hours. Time to event analysis was performed using a Log-Rank test with SPSS 19 (IBM, USA). Results: All results are presented as median (p25-p75) comparing CONTROL vs CONDITIONING groups respectively: KIDNEYTIME was 17 (13-20) vs 28 (22-30) p=0.033, LACTIME 18 (15-21) vs 25 (20-30) p=0.101, HYPOTENSIONTIME 17 (14-19) vs 28 (23-30) p<0.001 and DEATHTIME 25 (23-27) vs 30 (27-30) p=0.023. Conclusions: In this sheep model of severe abdominal sepsis, repeated ischemic pre- and post-conditioning of the pelvis and lower extremities resulted in improved hemodynamics, renal function and survival time.