Microcirculation and mitochondria in sepsis: getting out of breath.
OBJECTIVE
To present the recent findings obtained in clinical and experimental studies examining microcirculatory alterations in sepsis, their link to mitochondrial dysfunction, and current knowledge regarding the impact of these alterations on the outcome of septic patients.


RESULTS
Interlinked by a mutual cascade effect and driven by the host-pathogen interaction, microcirculatory and mitochondrial functions are impaired during sepsis. Mitochondrial respiration seems to evolve during the course of sepsis, demonstrating a change from reversible to irreversible inhibition. The spatiotemporal heterogeneity of microcirculatory and mitochondrial dysfunction suggests that these processes may be compartmentalized. Although a causal relationship between mitochondrial and microcirculatory dysfunction and organ failure in sepsis is supported by an increasing number of studies, adaptive processes have also emerged as part of microcirculatory and mitochondrial alterations. Treatments for improving or preserving microcirculatory, mitochondrial function, or both seem to yield a better outcome in patients.


CONCLUSIONS
Even though there is evidence that microcirculatory and mitochondrial dysfunction plays a role in the development of sepsis-induced organ failure, their interaction and respective contribution to the disease remains poorly understood. Future research is necessary to better define such relationships in order to identify therapeutic targets and refine treatment strategies.
Balestra
Gianmarco M
GM
Department of Translational Physiology, Academic Medical Center, Amsterdam, The Netherlands. balestrag@uhbs.ch
Legrand
Matthieu
M
Ince
Can
C
D002199:Capillary Permeability / Q000187:drug effects; D002317:Cardiovascular Agents / Q000627:therapeutic use; D045304:Cytochromes c / Q000627:therapeutic use; D004921:Erythropoietin / Q000627:therapeutic use; D006801:Humans; D008833:Microcirculation / Q000502:physiology*; D008928:Mitochondria / Q000378:metabolism / Q000502:physiology*; D028361:Mitochondrial Diseases / Q000188:drug therapy / Q000503:physiopathology*; D011064:Poly Adenosine Diphosphate Ribose / Q000037:antagonists & inhibitors; D011994:Recombinant Proteins; D018805:Sepsis / Q000188:drug therapy / Q000503:physiopathology*
D002317:Cardiovascular Agents; D011994:Recombinant Proteins; D004921:Erythropoietin; D011064:Poly Adenosine Diphosphate Ribose; D045304:Cytochromes c