A persistent HIF1�� expression has already been demonstrated in cases of lipopolysaccharide stimulation and during a sustained inflammatory response selleck chem inhibitor [25-28]. Such situations are obviously present in the study patients. A major inflammatory response is present in patients with shock due to the ischemia-reperfusion induced by the treatment of shock [23,29-33]. Because plasma lactate concentrations are not only dependent on production but also on its metabolism, we hypothesized that HIF1�� would be a better marker. Our study clearly shows that, at the bedside, lactate remains a better marker of shock than HIF1��. The quantity of protein may be a more accurate marker than the gene expression. Future studies need to clarify this point.HIF1�� is a biomarker of states of cellular hypoxia.
Its interest as a marker of outcomes in patients with shock has never been evaluated before. Nevertheless, our results show that, despite attractive speculations about biomarkers, clinical trials are crucial to evaluate their actual role [4,5]. In the present study, the expression of HIF1�� is markedly increased during shock states. The observed increase could be related to the tissue ischemia of shock states or to the inflammatory response. No relation was found between HIF1�� expression and oxygenation variables. However, our results show a trend toward an increased expression in patients with low levels of hemoglobin (Hb >8 g/dL: 109 (range: 84 to 174) HIF1�� copies versus Hb <8 g/dL: 161 (range: 74 to 270) HIF1�� copies; P = 0.4). Larger samples of patients would be required in order to validate this trend.
The expression of HIF1�� was wider than expected in our rationale. The wide dispersion of the values may be explained by the ultra-short half-life of HIF1��. This may have affected the power of the study.In our study, HIF1�� mRNA expression seems to fail to reflect hypoxia. Several hypotheses may explain this result. First, we measured the expression of HIF1�� mRNA in plasma. Actually, in the case of hypoxia, its expression may be more accurate in tissue than in blood. However, regarding our study goals, the collection of tissue biopsy was irrelevant. Second, we may hypothesize that the protein of HIF1�� may better reflect tissue hypoxia than its mRNA expression. However, the determination of the protein levels is time consuming, whereas that of RNA levels can be performed in a short time.
Our study was aimed at providing an early marker in real-life clinical practice. Finally, divergently from HIF1��, plasma lactate levels may reflect pyruvate accumulation rather than cell hypoxia in sepsis and injury [9]. The evaluation of HIF1�� values beyond four GSK-3 hours may also bring new evidence of its role in patients with shock. Future studies are needed to determine whether its expression during late phases of shock may be related to early interventions.