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Limb ischemic conditioning induces oxidative stress followed by a correlated increase of HIF-1α in healthy volunteers.

J. García-de-la-Asunción,Jaume Perez-Griera,T. Moreno,Alejandro Duca,Nuria García-del-Olmo,J. Belda,M. Soro

Published 2019 in Annals of Vascular Surgery

ABSTRACT

BACKGROUND Local and remote ischemic preconditioning has been used as a protective intervention against ischemia-reperfusion (I/R) damage in several preclinical and clinical studies. However, its physiological mechanisms are not completely known. I/R increases the production of reactive oxygen species, which also serve as messengers for variety of functions. Hypoxia inducible factor-1 alpha (HIF-1α) is probably the most important transcription factor mediator of hypoxic signaling. OBJECTIVE We hypothesized that limb ischemic conditioning (LIC) induces a local oxidative/nitrosative stress and a correlated increase of HIF-1α plasma levels. METHODS An observational, prospective and single center study has been conducted in 27 healthy volunteers. LIC was applied: 3 cycles (5 min ischemia followed by 5 min reperfusion) using an ischemia cuff placed on the upper left arm. Time course of 8-isoprostane, nitrite and HIF-1α levels were measured in blood plasma. Venous blood was sampled from the left arm before tourniquet inflation (basal) and after LIC: 1 min and 2 h for 8-isoprostane and nitrite; and 1 min, 2 h, 8 h, 24 h and 48 h for HIF-1α. RESULTS After LIC we have found an early increase of 8-isoprostane and nitrite. HIF-1α increased at 2 and 8 hours after LIC. We found a direct correlation between HIF-1α and 8-isoprostane and nitrite plasma levels. CONCLUSIONS We concluded that LIC induces an early oxidative/nitrosative stress in the arm followed by an increase of HIF-1α plasma levels correlated with 8-isoprostane and nitrite levels, possibly as a local response.

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