Hemodynamic evaluation of chemical mediators of sepsis during systemic inflammatory response in an experimental animal model

The early diagnosis of sepsis increases the chances of its successful treatment. Biomarkers are able to distinguish between systemic inflammatory response syndrome and sepsis and are used to monitor pro- and anti-inflammatory changes associated with the host response to pathogens. A total of 11 rats underwent sepsis induction and measured systolic, diastolic and mean arterial blood pressure. Leukocyte counts, procalcitonin, and nitric oxide also were measured 0, 2, and 4 hours after the induction of sepsis using the cecal ligation and puncture method. The animals were divided into two groups: control (SHAM) and induced. Procalcitonin levels remained within the normal range for an inflammatory response throughout the experiment. There was a statistically insignificant increase in nitric oxide levels. All animals showed increased diastolic arterial blood pressure; however, the increase in the induced animals was even more pronounced. Procalcitonin and nitric oxide levels can increase due to surgical manipulation, while arterial blood pressure was not a good predictor for the onset of sepsis during the time period studied here.


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Sepsis is a syndrome caused by an uncontrolled systemic inflammatory response 39 of the individual that is of bacterial, fungal, or viral origin. If not treated promptly, 40 sepsis progresses to septic shock, which is characterized by severe depletion of 41 intravascular volume and cellular hypoxia and can lead to multiple organ failure and 42 death [1]. 43 With a mortality rate of 30-50%, severe sepsis and septic shock are the major 44 causes of admission and death in the intensive care unit (ICU). In the United States, 45 751,000 cases and 215,000 deaths annually are estimated. In Brazil, the incidence is 57 3 46 per 1000 patients per day and the mortality rates of patients with severe sepsis and 47 septic shock are 47.3% and 52.2%, respectively [2]. 48 Although the symptoms are known, distinguishing the cause of sepsis in patients with 49 clinical signs of acute inflammation in the emergency room and ICU remains 50 problematic [3]. 51 The early recognition and treatment of sepsis contributes to recovery success 52 and, consequently, higher survival rates [1]. The presence of certain components in the 53 pathogen membrane induces the release of specific inflammatory mediators 54 characterizing the initial phase of sepsis. Biomarkers are able to distinguish between 55 SIRS and sepsis, and a strategy to monitor the pro-and anti-inflammatory changes 56 associated with the host response to pathogens [3].

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In recent years, researchers have consequently attempted to diagnose sepsis early 58 and change or interrupt its course. However, the poor clinical outcome and/or 59 continuing high mortality rates of patients with sepsis have not yet resulted in an 60 immediate or successful solution to this problem.

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The use of biomarkers has been suggested to assist with early diagnosis; 62 therefore, it may be an immediate appropriate therapy for patients with sepsis in the 63 ICU. A biomarker is an indicator of normal biological processes as well as the 64 pathogenic or pharmacological responses that may lead to a therapeutic intervention  Procalcitonin (PCT) is a biomarker encoded by the CALC-1 gene located on 67 chromosome 11. The mRNA is translated into pre-PCT and the product of this 68 translation is modified in PCT, a 116-amino-acid prohormone that is then converted into 69 calcitonin, an active 32-amino-acid hormone that is involved in calcium and 70 phosphorous metabolism [5]. In healthy patients, PCT is secreted almost exclusively by thyroid C-cells [5]; 72 under these conditions, the serum PCT concentrations are very low (0.05 ng/mL) [6][7]. 73 In the case of septicemia, particularly when associated with bacteremia, an alternative 74 pathway for PCT production may become activated that increases its serum levels. 75 Lung, colon, and spleen tissues can produce PCT in these cases [5]. Levels > 2 ng/mL 76 indicate susceptibility to developing severe sepsis or septic shock [7].

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PCT is considered a good clinical marker due to its high specificity and 78 sensitivity (8), and its serum levels increase within 3 hours, peaking at around 6-12 79 hours in addition to being highly stable in the serum and plasma [7]. It also has a half-     The animals were randomly divided into control (SHAM) and experimental 139 groups.

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In the SHAM group (n = 5), a laparotomy was performed and the cecum was

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The recovery of the anesthetic animals was normal and the tests could be 167 performed at the indicated time points. In both groups, the animals' WBC counts did not differ significantly, but a pattern 169 of leukocytosis at time point 2 and leukopenia at time point 3 could be observed (Fig.   170 1).

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The PCT values remained very similar between groups with values close to 2 172 ng/mL (Fig. 2).

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The NO levels showed progressive but insignificant increases at each time point 174 in both groups; in the induced group, the increase was even more pronounced (Fig. 3).  Soreng et al. [5], who claimed that surgeries, severe trauma, and burns are also capable 193 of increasing PCT levels.

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The animals were evaluated for only 4 hours, so it is possible that the PCT 195 values were not yet at its peak plasma concentration. According to Liu et al. [7], PCT 196 levels in humans increase over a period of 3 hours and peak at 6-12 hours. The time 197 frame for this response in rats was estimated to be 4 hours since this species has a 198 higher metabolic rate than humans. Accordingly, we estimated that the selected time 199 frame would be sufficient for determining sepsis.

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The NO levels did not show statistically significant differences between groups,  After the end of the experiment and data analysis, we can conclude that despite 236 PCT being a recommended biomarker for the diagnosis and prognosis of sepsis, its 237 production may be increased for other causes such as surgeries and trauma rather than 238 bacterial infections.

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The plasma NO concentration may be increased due to surgical manipulation. 240 Despite the fact that this biomarker promotes vasodilation, it is not related to mean 241 arterial hypotension.

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The use of arterial blood pressure as the only method of assessment was not a 243 good predictor of sepsis onset during the 4-hour study period. The results of diastolic 244 hypertension found in the present study are not consistent with those found in the 245 studies that cite hypotension in cases of septic shock.