Mitochondrial Changes in Platelets Are Not Related to Those in Skeletal Muscle during Human Septic Shock

Abstract

Platelets can serve as general markers of mitochondrial (dys)function during several human diseases. Whether this holds true even during sepsis is unknown. Using spectrophotometry, we measured mitochondrial respiratory chain biochemistry in platelets and triceps brachii muscle of thirty patients with septic shock (within 24 hours from admission to Intensive Care) and ten surgical controls (during surgery). Results were expressed relative to citrate synthase (CS) activity, a marker of mitochondrial density. Patients with septic shock had lower nicotinamide adenine dinucleotide dehydrogenase (NADH)/CS (p = 0.015), complex I/CS (p = 0.018), complex I and III/CS (p<0.001) and complex IV/CS (p = 0.012) activities in platelets but higher complex I/CS activity (p = 0.021) in triceps brachii muscle than controls. Overall, NADH/CS (r2 = 0.00; p = 0.683) complex I/CS (r2 = 0.05; p = 0.173), complex I and III/CS (r2 = 0.01; p = 0.485), succinate dehydrogenase (SDH)/CS (r2 = 0.00; p = 0.884), complex II and III/CS (r2 = 0.00; p = 0.927) and complex IV/CS (r2 = 0.00; p = 0.906) activities in platelets were not associated with those in triceps brachii muscle. In conclusion, several respiratory chain enzymes were variably inhibited in platelets, but not in triceps brachii muscle, of patients with septic shock. Sepsis-induced mitochondrial changes in platelets do not reflect those in other organs.

Mitochondrial Function in Sepsis

“…There are discrepancies in the literature with regards to changes in complex activity in different muscle groups and organs in sepsis (11,13) and endotoxemia (14–16). This discrepancy has been attributed to differences in the organs studied (16), the time point of measurement, species involved and severity of illness.…”

“…This discrepancy has been attributed to differences in the organs studied (16), the time point of measurement, species involved and severity of illness. Importantly, changes in endotoxemia differ from those observed following CLP.…”

“…Respiratory chain biochemistry in platelets is variably inhibited, with no convincing association with either severity of illness or mortality (16). Reduced complex activity in platelets is not a consistent finding (44), and may be time-dependent.…”

New Prognostic Biomarkers of Mitochondrial Oxidative Stress in Septic Patients

“…The function of the OXPHOS system in septic patients has been analyzed only in studies with small sample sizes (fewer than 40 septic patients and 40 control subjects), and the results are demonstrably inconsistent (67)(68)(69)(70)(71)(72)(73)(74)(75)(76)(77)(78)(79)(80)(81)(82). Some studies have found lower activity of different mitochondrial respiratory complexes in septic patients than in control subjects in muscle biopsies (ie, biceps brachii, triceps brachii, vastus lateralis, serratus anterior), peripheral blood mononuclear cells, and circulating platelets.…”

Assessment of Mitochondrial Respiration in Human Platelets

“…The study by Sjovall et al demonstrated that mitochondrial uncoupling parallel with a gradual and pronounced increase in mitochondrial respiratory capacity was negatively correlated with the clinical outcome in patients with sepsis, suggesting that platelet mitochondrial function can potentially be used as a biomarker for the severity of sepsis [26]. Interestingly, recent data showed that sepsis-induced mitochondrial changes in platelets (i.e., a decrease in CI, II, III and IV activity) [27] were not accompanied by mitochondrial changes in other organs, suggesting that platelets' energetic ability may be a marker of sepsis progression [28]. Thus, the assessment of the platelet energetic profile have emerged as potential biomarker for both presence and prognostic of the disease.…”