Early protective effect of total hypoxic preconditioning on rats against systemic injury from hemorrhagic shock and resuscitation.

Abstract

BACKGROUND:

In vivo or in vitro hypoxic preconditioning (HPC) can protect various tissues and cells against subsequent ischemia and/or reperfusion (hypoxia and/or reoxygenation) injury. Total HPC (THPC) in animal models is largely aimed at protecting single organs; however, scant data exist on whole body protection. The present study investigated whether THPC could protect anesthetized rats against the systemic injury induced by hemorrhagic shock and resuscitation (HS/R).

METHODS:

The 4-cycle THPC protocol consisted of 5 min of inhalation hypoxia (fraction of inspired oxygen 10%, N(2) 90% plus oxygen 10%) followed by 10 min of inhalation air (oxygen 21%). An acute HS/R model of anesthetized rats was used. The experiment was divided into two parts of the Severe HS/R and Moderate HS/R, differentiated by a shed blood volume of 60% or 50% (HS/R(60%) or HS/R(50%), respectively) of the total blood volume of rats, respectively. In the Severe HS/R part, the heart rate, respiration rate, and mean arterial pressure of the rats were measured, and the survival of the rats was observed. We examined the pathomorphologic changes in the vital organs of rats and measured the arterial blood gas, heart rate, respiration rate, and mean arterial pressure of the rats in the Moderate HS/R part.

RESULTS:

THPC did not result in irreversible changes or death in the rats. The rats in the THPC + HS(60%)/R group had a significantly greater survival rate than those in the HS(60%)/R group (59% versus 33%, log-rank test, chi-square = 4.356, P = 0.037). The histopathologic lung score of the rats in the HS(50%)/R group (1.7 ± 0.5) was significantly greater than that in the THPC + HS(50%)/R (1.1 ± 0.6, P = 0.046). The arterial blood gas pH was lower in the HS(50%)/R group than in the THPC + HS(50%)/R group. THPC had a greater influence on the arterial partial pressure of oxygen and carbon dioxide than on bicarbonate radical and base excess. The respiration rate in the THPC + HS/R group was faster than that in the HS/R group. No significant differences in heart rate or mean arterial pressure were seen between the THPC + HS/R and HS/R groups.

CONCLUSIONS:

In anesthetized rats, THPC provided early protection against the subsequent systemic injury caused by hemorrhagic shock following resuscitation. THPC might exert systemic protection by improving the function of vital organs (e.g., lungs and, perhaps, the brain).