Higher platelet cytochrome oxidase specific activity in surviving than in non-surviving septic patients

Abstract

IntroductionIn a previous study with 96 septic patients, we found that circulating platelets in 6-months surviving septic patients showed higher activity and quantity of cytochrome c oxidase (COX) normalized by citrate synthase (CS) activity at moment of severe sepsis diagnosis than non-surviving septic patients. The objective of this study was to estimate whether COX specific activity during the first week predicts 1-month sepsis survival in a larger cohort of patients.MethodsUsing a prospective, multicenter, observational study carried out in six Spanish intensive care units with 198 severe septic patients, we determined COX activity per proteins (COXact/Prot) in circulating platelets at day 1, 4 and 8 of the severe sepsis diagnosis. Endpoints were 1-month and 6-months mortality.ResultsSurvivor patients (n = 130) showed higher COXact/Prot (P < 0.001) than non-survivors (n = 68) at day 1, 4 and 8 of severe sepsis diagnosis. More than a half of the 6-months survivor patients showed an increase in their COXact/Prot from day 1 to 8. However, most of the 1-month non-survivors exhibited a decrease in their COXact/Prot from day 1 to 8. Multiple logistic regression analyses showed that of platelet COXact/Prot > 0.30 mOD/min/mg at day 1 (P = 0.002), 4 (P = 0.006) and 8 (P = 0.02) was associated independently with 1-month mortality. Area under the curve of COXact/Prot at day 1, 4 and 8 to predict 30-day survival were 0.70 (95% CI = 0.63-0.76; P < 0.001), 0.71 (95% CI = 0.64-0.77; P < 0.001) and 0.71 (95% CI = 0.64-0.78; P < 0.001), respectively.ConclusionsThe new findings of our study, to our knowledge the largest series reporting data about mitochondrial function during follow-up in septic patients, were that septic patients that survive 1-month have a higher platelet cytochrome oxidase activity at moment of sepsis diagnosis and during the first week than non-survivors, and that platelet cytochrome oxidase activity at moment of sepsis diagnosis and during the first week could be used as biomarker to predict the clinical outcome in septic patients.

Cellular metabolism of myeloid cells in sepsis

“…Moreover, data in the literature on total body oxygen consumption are variable, with some studies showing increased consumption in severe sepsis (but lower than in uncomplicated sepsis) [75], whereas others have reported decreased oxygen consumption [76]. In a study with almost 200 sepsis patients, complex-V activity (of the ETC) of platelets was decreased compared with healthy controls [77][78][79]. Reduced complex-V activity was also observed in a polymicrobial murine sepsis model.…”

High central venous oxygen saturation is associated with mitochondrial dysfunction in septic shock: A prospective observational study

“…Both human and animal studies also demonstrated that the severity of mitochondrial dysfunction in sepsis was higher than that in cases of hypovolemic and cardiogenic shock, 21,22 thus indicating the impact of the systemic inflammatory process on mitochondrial dysfunction. A recent study reported that in the early phase of sepsis (Days 1‐4) increased mitochondrial respiratory activity (complex IV; cytochrome oxidase activity per proteins) is associated with improved survival rate 6 . Moreover, it has been shown that increased late phase (Days 6‐7) activity of mitochondrial respiration (complex I and II) is associated with lower survival rates 23 .…”

Platelet Proteome Changes in Dogs with Chronic Heart Failure

“…Since COX enzyme handles more than 90% of molecular oxygen produced by the mammalian cells and tissue (47), low COX-II levels may be a factor in the emergence of exercise intolerance and/or respiratory stress in dogs with CHF, as reported in humans (49). Platelet COX activity enhancing drugs may have a potential to limit the progression of adverse cardiac remodeling and heart failure, as suggested for septic patients with low COX activity (50).…”