ISCHEMIC CONDITIONING PROTECTS THE MICROCIRCULATION, PRESERVES ORGAN FUNCTION, AND PROLONGS SURVIVAL IN SEPSIS

Ischemic conditioning induces a series of cellular modifications that may prevent injury from further hypoxic episodes, but there are few data in sepsis. In this randomized controlled study, we evaluated the effects of ischemic conditioning on the microcirculation, organ function, and survival time in an ovine model of septic shock.Sepsis was induced in 14 anesthetized, mechanically ventilated adult sheep by injecting autologous feces into the abdominal cavity. Animals were then randomized to ischemic pre- and post-conditioning or no conditioning (both n=7). Remote ischemic conditioning was performed by inflating the balloon of a catheter in the aortic bifurcation for 2 min, followed by a 4-min deflation period. The procedure was performed four times before sepsis induction and 4-hourly afterward. Animals were followed until death or for a maximum of 30h. Hemodynamic, oxygenation, and microcirculatory variables were monitored. The conditioned group had higher mixed venous oxygen saturation from 8h after randomization, higher cardiac index, and oxygen delivery from 16h, and higher mean arterial pressure and lower lactate levels from 20h. They also had greater renal blood flow, urine output, and creatinine clearance. Microcirculatory variables were better preserved in the conditioned than in the control group from 6h after randomization: the median proportion of perfused vessels was 91 (89-93)% versus 89 (86-90)% (P=0.024) and there was less heterogeneity. Oliguria, hypotension, and death occurred later in the conditioned than in the control group. In this sepsis model, remote ischemic pre- and post-conditioning therefore decreased organ dysfunction, preserved the microcirculation, and prolonged survival.