Clemens, Mark G. PhD
University of North Carolina at Charlotte, Charlotte, North Carolina
Shock once again offers an excellent array of clinical and laboratory reports, this month with a particular emphasis on biomarkers on monitoring methods. The lead article is a review by Niesler et al. (1) on alveolar macrophages following trauma. Lung injury is a very common event following trauma; this article provides an excellent critical overview of the mechanisms by which activated alveolar macrophages may contribute to injury and should serve as a definitive reference in the area. This month also offers 3 clinical reports. Yang et al. (2) performed a retrospective review of Chinese blunt trauma patients and compared outcomes for male and female patients of different ages and injury severity. Their results showed that in this Chinese population females had lower mortality rates than did males and that this was most pronounced for those younger than 50 years and with injury severity score of more than 25, indicating the importance of sex hormones in response to severe injury. An important aspect of care of critically injured patients is being able to accurately assess their status. The July issue of Shock offers two clinical studies and several laboratory studies that address this issue. Popovic et al. (3) performed a retrospective review of 85 patients with cardiogenic shock to determine early predictors of mortality. Their analysis showed that initial cardiac power index and mean arterial pressure of less than 75 mmHg at 6 h after entering the intensive care unit were significant and independent predictors of mortality. Adrenal insufficiency is thought to be a potential contributor to pathology in sepsis but remains controversial. Therefore, Festti et al. (4) performed a prospective study on 34 patients with septic shock receiving pressors of 7,324 monitored patients, monitoring components of the cortisol pathway as well as cholesterol and lipoproteins as potential markers of adrenal insufficiency. They found adrenal insufficiency in 32.4% of the patients with sepsis and total cholesterol, high-density lipoprotein, triglycerides, and salivary cortisol were not different based on adrenal status. However, baseline endogenous adrenal corticotropic hormone was higher with adrenal insufficiency, indicating that it may be a useful biomarker for this complication.
Continuing the theme of biomarkers into the laboratory setting, Xu et al. (5) used proteomic analysis of plasma following liver transplantation in a rat model to search for markers of acute rejection. Their results showed a particular downregulation of hemopexin in acute rejection suggesting its utility as a biomarker. Moreover, the effect of hemopexin on lymphocytes suggested a functional deficiency. They propose that treatment with hemopexin may help to normalize cytokine expression in lymphocytes. Continuing on the theme of proteomic analysis, Jiao et al. (6) analyzed serum from rats at 12 h following cecal ligation and puncture stratified based on survival. They found 47 proteins preferentially expressed in sepsis and 28 preferentially expressed in nonsurvivors. Further logistic regression identified four proteins (multimerin 1, proplatelet basic protein, fibrinogen α, and fibrinogen β) that may be useful for prognosis of sepsis.
In addition to biomarkers, advance in monitoring approaches can aid in the management of critically ill patients. Two articles this month discuss methods for monitoring aspects of gas exchange. Belenkiy et al. (7) studied methods for monitoring PCO2 status as a parameter for ventilator control in a swine model of hemorrhagic shock. They found that with hemorrhage none of the noninvasive PCO2 monitoring systems correlated with arterial PCO2. However the difference between end-tidal CO2 and transcutaneous PCO2 correlated much better with degree of blood loss and showed better correlation with plasma lactate levels, suggesting that this approach might be a more useful and noninvasive parameter to guide ventilator settings in hemorrhagic shock. In a similar sort of study, Soller et al. (8) examined skeletal muscle pH and muscle oxygen saturation (SmO2) measured noninvasively by infrared spectrometry as indicators of adequacy of resuscitation in a swine model. pH and SmO2 agreed well with each other both at the end of the resuscitation and the end of the study in both survivors and nonsurvivors; however, each measurement was different between survivors and nonsurvivors at the end of the resuscitation period, suggesting that they may be useful for guiding adequacy of resuscitation. The final methods-oriented article this month by del Pilar Huby et al. (9) examined the effect of the method of blood sampling on coagulation factors in rats. They compared coagulation in blood taken by cardiac puncture to that taken via arterial catheterization. The two different sampling procedures resulted in significant differences in coagulation, with cardiac puncture samples demonstrating hypercoagulability. The authors advise that it is essential for blood sampling methods to be standardized to be able to compare results of studies on coagulopathies in shock.
Toll-like receptor (TLR) signaling has been extensively studied in shock. The July issue of Shock presents two more contributions to our knowledge on TLR effects. Zhang et al. (10) examined the role of TLR4 in mediating cardiac contractile dysfunction in a trauma/hemorrhage model in mice. Cardiac function was depressed after trauma/hemorrhage in wild-type mice but not in TLR4−/−. This protection could be mimicked with administration of a TLR4 antagonist. The protection appeared to be the result of activation of the PI3 kinase/Akt and inhibition of nuclear factor κB. In addition to TLR4, TLR2 has been implicated in injury. Kuipers et al. (11) investigated the effect of TLR2 deficiency on ventilator injury in the lung. In both bronchoalveolar lavage cells in human patients and lung tissue in ventilated mice, TLR2 gene expression was enhanced. Mechanical ventilation in wild-type mice resulted in inflammation with neutrophil infiltration, and this was enhanced in TLR2−/− mice. Thus, TLR2 expression is increased with ventilator injury, but deletion of TLR2 actually exacerbates the injury.
The final article this month from Niño et al. (12) examined the effects of the antifungal agent itraconazole on phagocytosis by macrophages. They found that itraconazole significantly impaired mouse macrophage phagocytosis and that this was associated with a downregulation of cell surface Fcγ receptors. The authors conclude that this effect on macrophage function may result in impaired pathogen clearance in vivo and thus contribute to increased incidence of infections.
1. Niesler U, Palmer A, Radermacher P, Huber-Lang MS: Role of alveolar macrophages in the inflammatory response after trauma. Shock 42: 3–10, 2014.
2. Yang K-C, Zhou M-J, Sperry JL, Rong L, Guang X, Zhu L-G, Wu W, Zhao G, Billiar TR, Feng Q-M: Significant sex-based outcome differences in severely injured Chinese trauma patients. Shock 42: 11–15, 2014.
3. Popovic B, Fay R, Cravoisy-Popovic A, Levy B: Cardiac power index, mean arterial pressure and SAPS II are strong predictors of survival and response to revascularization in cardiogenic shock. Shock 42: 22–26, 2014.
4. Festti J, Grion CMC, Festti L, Mazzuco TL, Lima-Valassi HP, Brito VN, Barbosa DS, Carrilho AJF: Adrenocorticotropic hormone but not high-density lipoprotein cholesterol or salivary cortisol was a predictor of adrenal insufficiency in patients with septic shock. Shock 42: 16–21, 2014.
5. Xu M, Tan C, Hu J, Alwahsh SM, Yan J, Hu J, Dai Z, Wang Z, Zhou J, Fan J, et al.: Expression of hemopexin in acute rejection of rat liver allograft identified by serum proteomic analysis. Shock 42: 65–73, 2014.
6. Jiao J, Gao M, Zhang H, Wang N, Xiao Z, Liu K, Yang M, Wang K, Xiao X: Identification of potential biomarkers by serum proteomics analysis in rats with sepsis. Shock 42: 74–80, 2014.
7. Belenkiy SM, Berry JS, Batchinsky AI, Kendrick C, Necsoiu C, Jordan BS, Salinas J, Cancio LC: The non-invasive carbon dioxide gradient (NICO2G) during hemorrhagic shock. Shock 42: 38–43, 2014.
8. Soller B, Smith C, Zou F, Ellerby GEC, Prince MD, Sondeen JL: Investigation of noninvasive muscle pH and oxygen saturation during uncontrolled hemorrhage and resuscitation in swine. Shock 42: 44–51, 2014.
9. del Pilar Huby M, Cardenas JC, Baer LA, Pawelczyk NS, Salsbury JR, Wang Y-WW, Matijevic N, Holcomb JB, Wade CE: Establishment of methods for performing thrombelastography and calibrated automated thrombography in rats. Shock 42: 27–30, 2014.
10. Zhang X, Lu C, Gao M, Cao X, Ha T, Kalbfleisch JH, Williams DL, Li C, Kao RL: Toll-like receptor 4 plays a central role in cardiac dysfunction during trauma hemorrhage shock. Shock 42: 31–37, 2014.
11. Kuipers MT, Jongsma G, Hegeman MA, Tuip-de Boer AM, Wolthuis EK, Choi G, Bresser P, van der Poll T, Schultz MJ, Wieland CW: TLR2 deficiency aggravates lung injury caused by mechanical ventilation. Shock 42: 60–64, 2014.
12. Niño DF, Cauvi DM, de Maio A: Itraconazole, a commonly used antifungal, inhibits Fcγ receptor-mediated phagocytosis: alteration of Fcγ receptor glycosylation and gene expression. Shock 42: 52–59, 2014.