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

  • Wangde DaiEmail author
  • Jianru Shi
  • Juan Carreno
  • Sharon L. Hale
  • Robert A. Kloner



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 200 mmHg for 5 min, followed by 5-min release of the cuffs (repeated for 4 cycles), or control group (cuffs were inflated to 30 mmHg). Hemorrhagic shock was induced by withdrawing blood to a fixed mean blood pressure of 30 mmHg for 30 min, followed by 30 min of resuscitation with shed blood. Rats remained anesthetized for 1 h during which hemodynamics were monitored then they were allowed to survive for 6 weeks.


The percentage of estimated total blood volume withdrawn to maintain a level of 30 mmHg was similar in both groups. RIPC significantly increased survival at 6 weeks: 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 1 h 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 1 h after initiation of resuscitation. Blood urea nitrogen (BUN) was within normal range in the RIPC group (17.3 ± 1.2 mg/dl) but elevated in the control group (22.0 ± 1.7 mg/dl) at 48 h 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.


Hemorrhagic shock Remote ischemic preconditioning 


Funding Information

This work was supported by the Office of the Assistant Secretary of Defense for Health Affairs, through the Peer Reviewed Medical Research Program under Award No.W81XWH-16-1-0606.

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

Ethical Approval

All applicable international, national, and/or institutional guidelines for the care and use of animals were followed.


Opinions, interpretations, conclusion, and recommendations are those of the authors and are not necessarily endorsed by the Department of Defense.

Supplementary material

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Wangde Dai
    • 1
    • 2
    Email author
  • Jianru Shi
    • 1
    • 2
  • Juan Carreno
    • 1
  • Sharon L. Hale
    • 1
  • Robert A. Kloner
    • 1
    • 2
  1. 1.HMRI Cardiovascular Research Institute, Huntington Medical Research InstitutesPasadenaUSA
  2. 2.Division of Cardiovascular Medicine of the Keck School of MedicineUniversity of Southern CaliforniaLos AngelesUSA

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