Improved Long-term Survival with Remote Limb Ischemic Preconditioning in a Rat Fixed-Pressure Hemorrhagic Shock Model.

Abstract

We investigated whether bilateral, lower limb remote ischemic preconditioning (RIPC) improved long-term survival using a rat model of hemorrhagic shock/resuscitation. Rats were anesthetized, intubated and ventilated, and randomly assigned to RIPC, induced by inflating bilateral pressure cuffs around the femoral arteries to 200mmHg for 5min, followed by 5-min release of the cuffs (repeated for 4cycles), or control group (cuffs were inflated to 30mmHg). Hemorrhagic shock was induced by withdrawing blood to a fixed mean blood pressure of 30mmHg for 30min, followed by 30min of resuscitation with shed blood. Rats remained anesthetized for 1h during which hemodynamics were monitored then they were allowed to survive for 6weeks. The percentage of estimated total blood volume withdrawn to maintain a level of 30mmHg was similar in both groups. RIPC significantly increased survival at 6weeks: 5 of 27 (19%) rats in the control group and 13 of 26 (50%; p = 0.02) rats in the RIPC group survived. Blood pressure was higher in the RIPC group. The diastolic internal dimension of the left ventricle, an indicator of circulating intravascular blood volume, was significantly larger in the RIPC group at 1h after initiation of resuscitation compared to the control group (p = 0.04). Left ventricular function assessed by fractional shortening was comparable in both groups at 1h after initiation of resuscitation. Blood urea nitrogen (BUN) was within normal range in the RIPC group (17.3 ± 1.2mg/dl) but elevated in the control group (22.0 ± 1.7mg/dl) at 48h after shock. RIPC significantly improved short-term survival in rats that were subjected to hemorrhagic shock, and this benefit was maintained long term. RIPC led to greater circulating intravascular blood volume in the early phase of resuscitation and improved BUN.