Remote limb ischemic preconditioning improves post‐resuscitation long term survival in a rat fixed pressure hemorrhagic shock model

Abstract

BackgroundWe investigated whether bilateral lower limb remote ischemic preconditioning (RIP) could improve long‐term survival in a rat model of hemorrhagic shock/resuscitation.MethodsSprague Dawley rats (both genders) were anesthetized with intraperitoneal ketamine and xylazine, and were intubated and ventilated with room air. Rats were randomly assigned to RIP (n= 26; induced by inflating small bilateral pressure cuffs to 200 mmHg around the femoral arteries for 5 minutes, followed by 5 minute release of the cuffs, repeated 4 times) or control group (n= 27; the blood pressure cuffs are inflated only to 30 mmHg). After heparinization, hemorrhagic shock was induced by withdrawing blood from the left carotid artery to a fixed mean blood pressure of 30 mmHg for 30 minutes, followed by 30 min of resuscitation with shed blood. Rats remained anesthetized for one hour during which hemodynamics were monitored (femoral artery catheter); and then allowed to survive for 6 weeks.ResultsThe survival rate at 6 weeks was 5 out of 27 rats in the control group (18.5%), and 13 out of 26 rats in the RIP group (50%; p<0.05 by Fisher's exact test). Recovery of blood pressure during the early resuscitation phase was significantly improved and the heart rate was significantly lower in the RIP group compared to the control group (Figure below). At 6 weeks, all of the surviving rats were neurologically intact. Histochemistry/histologic staining was performed in the tissues from 9 survived rats, and showed brain infarction in 1 out of 3 rats in control and 1 out of 6 rats in RIP group; no evidence of myocardial or kidney infarction were detected.ConclusionsRIP markedly and significantly improved long term survival after experimental hemorrhagic shock/resuscitation and improved recovery of blood pressure in the early phase of resuscitation.Support or Funding InformationThis 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. Opinions, interpretations, conclusion and recommendations are those of the authors and are not necessarily endorsed by the Department of Defense.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.