There is a direct correlation between the development of the multiple organ dysfunction syndrome (MODS) and the elevated mortality associated with sepsis. The mechanisms responsible for MODS development are being studied, however, the main efforts regarding MODS evaluation have focused on oxygen delivery optimization and on the modulation of the characteristic inflammatory cascade of sepsis, all with negative results. Recent studies have shown that there is development of tissue acidosis, even when there are normal oxygen conditions and limited presence of tissue cellular necrosis or apoptosis, which would indicate that cellular energetic dysfunction may be a central element in MODS pathogenesis. Mitochondrias are the main source of cellular energy, central regulators of cell death and the main source for reactive oxygen species. Several mechanisms contribute to mitochondrial dysfunction during sepsis, that is blockage of pyruvate entry into the Krebs cycle, oxidative phosphorylation substrate use in other enzymatic complexes, enzymatic complex inhibition and membrane damage mediated by oxidative stress, and reduction in mitochondrial content. Hypoxia-inducible factor-1α (HIF-1α) is a nuclear transcription factor with a central role in the regulation of cellular oxygen homeostasis. Its induction under hypoxic conditions is associated to the expression of hundreds of genes that coordinate the optimization of cellular oxygen delivery and the cellular energy metabolism. HIF-1α can also be stabilized under normoxic condition during inflammation and this activation seems to be associated with a prominent pro-inflammatory profile, with lymphocytes dysfunction, and to a reduction in cellular oxygen consumption. Further studies should establish a role for HIF-1α as a therapeutic target.
y un derivado del mencionado péptido, seleccionándose el mencionado péptido entre el grupo constituido por: una sal de adición de ácido farmacéuticamente aceptable del mencionado péptido; and a derivative of said peptide, said peptide being selected from the group consisting of: an addition salt of pharmaceutically acceptable acid of said peptide; una sal carboxilato farmacéuticamente aceptable del mencionado péptido; a pharmaceutically acceptable carboxylate salt mentioned peptide; un éster de alquilo inferior farmacéuticamente aceptable del mencionado péptido; a pharmaceutically acceptable lower alkyl ester of said peptide; y una amida farmacéuticamente aceptable del mencionado péptido seleccionada entre amida, alquil inferior amida y dialquil inferior amida. and a pharmaceutically acceptable amide of said peptide selected from amide, lower alkyl amide and lower dialkyl amide.