"Inflammatory response to colloids compared to crystalloid priming in cardiac surgery patients with cardiopulmonary bypass"

"Cardiac surgery with cardiopulmonary bypass (CPB) induces a systemic inflammatory response syndrome that may contribute to postoperative morbidity and mortality. We investigated the in-flammatory responses to colloids compared to crystalloid priming in cardiac surgery patients with cardiopulmonary bypass. Thirty patients undergoing coronary artery bypass grafting (CABG) preparing for CPB were randomized into Ringer's solution (RS), 10% hydroxyethyl starch (HES) or 25% human albumin (HA) group. Serum concentrations of tumor necrosis factor-α (TNF-α), interleukin-1 β (IL-1β ), interleukin-6 (IL-6) and interleukin-10 (IL-10) were measured before CPB, at the end of CPB and 1, 6 and 12 h after CPB. Serum C-reactive protein (CRP) was determined pre-operatively and then daily for 2 days. Body-weight gain was significantly decreased on the day after surgery in the HES group than in the RS group. Volume priming in CPB for CABG patients using HA or HES preparation had less tendency for intense inflammatory response with lower levels of TNF-α, IL-1 β , IL-6 and higher levels of IL-10 compared to patients treated with RS. HES prime had lower levels of circulating CRP than in patients treated with HA or Ringer prime on the second post-operative day. Our data indicate that volume priming using colloid during CPB in CABG patients might exert beneficial effects on inflammatory responses."     

Effect of catecholamines on intracellular cytokine synthesis in human monocytes.

Proinflammatory cytokines produced by monocytes, like Interleukin-6 (IL-6), Interleukin-8 (IL-8), and tumor necrosis factor (TNF-alpha) are known for their pivotal role in the initiation of the inflammatory response following cardiopulmonary bypass (CPB). Catecholamines like epinephrine (Epi) and norepinephrine (Nor) are often necessary to stabilize the cardiac function in the early postoperative period and may influence the cytokine expression in monocytes. In this study we investigated the effects of Epi and Nor on IL-6, IL-8 and TNF-alpha expression in human monocytes stimulated with lipopolysaccharide (LPS) in whole blood, analyzed intracellularly by flow cytometry. Kinetics of intracellular proinflammatory cytokine production and LPS ED(50) were obtained. To simulate different stages of inflammation in vivo, varying concentrations of LPS (0.2 ng/ml, 1 ng/ml and 10 ng/ml) were used for stimulation. After a stimulation with LPS TNF-alpha was the first produced cytokine, followed by IL-8 and IL-6. All cytokines peaked from 3 h to 6 h. Epi and Nor had comparable effects on the expression of IL-6, IL-8 and TNF-a in monocytes. Both inhibited IL-6 and TNF-alpha expression in a concentration dependent manner whereas IL-8 expression remained unchanged. We conclude that monocytes are targets for Epi and Nor concerning their cytokine expression. The inhibiting effects of Nor and Epi were almost identical for all cytokines. Cytokine expression was affected most at low LPS concentrations.     

Cytokine secretion after cardiac surgery and its relationship to postoperative fever

A relationship between the inflammatory response to cardiopulmonary bypass (CPB) and fever after coronary artery bypass graft surgery (CABG) is assumed, but has not been studied. Therefore, we sought to assess the temporal pattern of cytokines' elevation and its association with post-CABG fever. In 355 primary elective CABG patients, serum cytokines (TNF-alpha, IL-1ra, IL-1beta, IL-6, and IL-8) were measured before surgery, at cessation of CPB and 2.5, 4.5, 24, and 48 h post-CPB. Fever was defined as a temperature >38 degrees C. TNF-alpha, IL-1beta and IL-8 peaked within the first 2.5 h after bypass, returning to near normal levels by 24h and increasing again by 48 h. IL-6 peaked early after bypass and remained elevated at 48 h. IL-1ra was elevated early, before returning to baseline by 24 h. Postoperative fever developed in 27% of patients. Increased IL-6 levels and male gender were significant predictors of fever (C-index=0.68; p=0.0003). No other cytokine showed a significant association with fever development. Of note is the previously undescribed bimodal pattern of cytokines' secretion after CABG. The association of fever with IL-6 levels suggests inflammatory mediation.     

Plasma and urinary cytokine homeostasis and renal function during cardiac surgery without cardiopulmonary bypass

Cardiopulmonary bypass (CPB) significantly contributes to the plasma pro-inflammatory cytokine response at cardiac surgery. Complementary plasma and urinary anti-inflammatory cytokine responses have been described. The pro-inflammatory cytokines interleukin 8 (IL-8), tumour necrosis factor alpha (TNF-alpha) and interleukin 1beta (IL-1beta) have lower molecular weights than the anti-inflammatory cytokines interleukin 10 (IL-10), interleukin 1 receptor antagonist (IL-1ra) and TNF soluble receptor 2 (TNFsr2) and thus undergo glomerular filtration more readily. In vitro work suggests that proximal tubular cells are vulnerable to pro-inflammatory cytokine mediated injury. Accordingly, this study investigated the hypothesis that cardiac surgery without CPB would not have significant changes in plasma and urinary cytokines and proximal renal dysfunction. Eight patients undergoing coronary artery bypass grafting (CABG) without CPB were studied. Blood and urine samples were analysed for pro- and anti-inflammatory cytokines. Proximal tubular dysfunction was measured using urinary Nu-acetyl-beta-D-glucosaminidase (NAG)/creatinine and alpha(1)-microglobulin/creatinine ratios. Plasma IL-8, IL-10, IL-1ra and TNFsr2 were significantly elevated compared with baseline. Urinary IL-1ra and TNFsr2 were significantly elevated, as were urinary NAG/creatinine and alpha(1)-microglobulin/creatinine ratios. Two hours following revascularization, urinary IL-1ra correlated with urinary alpha(1)-microglobulin/creatinine ratios (P<0.05). As previously reported in CABG surgery with CPB, we now report that non-CPB cardiac surgery also has significant changes in plasma and urinary cytokine homeostasis and early proximal tubular injury. The correlation between urinary IL-1ra and alpha(1)-microglobulin/creatinine ratios is consistent with earlier suggestions of a mechanistic link between cytokine changes and proximal tubular dysfunction. The relative roles of CPB and non-CPB processes in producing inflammation still require definition.     

Urinary soluble IL-6 receptor levels after cardiopulmonary bypass

To investigate the possible role of soluble interleukin 6 receptor (sIL-6r) in the inflammatory response to cardiopulmonary bypass (CPB) with extracorporeal circulation (ECC), we examined the levels of sIL-6r in the urine of 50 patients undergoing coronary artery bypass surgery. The presence of sIL-6r in urine was confirmed in these patients, with levels rising from 6 pg/ml preoperatively to 19.5 pg/ml at 6 h and 41 pg/ml at 24 h after the start of cardiopulmonary bypass. Cardiopulmonary bypass leads to a rise in sIL-6r in urine that has not returned to normal after 24 h, suggesting a role for sIL-6r and IL-6 in the inflammatory response to such surgery. Determination of cytokine receptor presence in urine offers a non-invasive approach to the monitoring of the immune and inflammatory response to the stress of surgical and traumatic injury.     

Pravastatin immunomodulates IL-6 and C-reactive protein, but not IL-1 and TNF-alpha, in cardio-pulmonary bypass

BACKGROUND: While statins are increasingly used in cardiopulmonary bypass (CPB), the anti-inflammatory effects of individual statins, within the context of various treatment regimes, need further examination. The present study evaluates the anti-inflammatory effectiveness of the short-term, preoperative and intensive postoperative use of pravastatin in CPB. METHOD: Forty three patients undergoing CPB were enrolled in a randomized, prospective clinical study. One group (n = 21), received pravastatin, the other (n = 22) did not. Patients in the pravastatin group received one dose of 40 mg per day for nine days, starting 48 hours before CPB, with an additional dose of 40 mg one hour after surgery. Plasma levels of selected inflammatory mediators were measured at baseline and tracked systematically. RESULTS: Pravastatin reduced postoperative interleukin-6 (IL-6) levels significantly at 24 and 48 hours, and at seven days. Mean +/- SD values, for treated versus untreated patients were: at 24 hours, 159.5 +/- 58.5 versus 251.2 +/- 53.0 pg/mL (p < 0.001); at 48 hours, 81.9 +/- 31.5 versus 194.2 +/- 56.3 pg/mL (p < 0.001); and at seven days, 16.4 +/- 7.2 versus 30.8 +/- 12.6 (p < 0.001). C-reactive protein (CRP) decreased significantly on the seventh postoperative day, when plasma levels were 3.6 +/- 1.1 in the treated patients versus 8.2 +/- 2.1 mg/dL in the controls (p < 0.001). No changes in plasma IL-1 and TNF-alpha were found during entire study. CONCLUSIONS: Pravastatin induced a precocious modulation of IL-6 expression and a later reduction of plasma CRP levels. Pravastatin;s effects on the expression of these pivotal inflammatory mediators strongly support its well-timed use in CPB.     

Increases in leukocyte cluster of differentiation antigen expression during cardiopulmonary bypass in patients undergoing heart transplantation

Cardiopulmonary bypass (CPB) is essential in heart transplantation surgery. It is also used in coronary artery grafting surgery where it has been associated with a postoperative inflammatory response. This manifests as an increase in pro-inflammatory proteins like interleukin-8 and tumour necrosis factor alpha accompanied by increases in neutrophil populations and increased expression of cluster of differentiation (CD) antigens. The latter have been investigated using flow cytometry, which is limited to the measurement of three to four CD antigens simultaneously. We have developed a novel antibody array that can simultaneously measure the expression of 72 different CD antigens. The purpose of this study was to use this technology to measure CD antigen expression in patients undergoing CPB during heart transplantation. Twelve patients undergoing this operation were studied. A preoperative sample acted as an internal control while a second sample taken during CPB was the comparator. No previous studies have examined changes in CD antigen expression during heart transplantation. We report an increase in the expression of 10 different CD antigens across all patients between the two time points.     

Reduced atrial connexin43 expression after pediatric heart surgery

Myocardial dysfunction and arrhythmias may be induced by congenital heart defects, but also be the result of heart surgery with cardiopulmonary bypass (CPB), potentially caused by differential expression of connexin40 (Cx40) and connexin43 (Cx43). In 16 pediatric patients undergoing corrective heart surgery, connexin mRNA expression was studied in volume overloaded (VO group, n=8) and not overloaded (NO group, n=8) right atrial myocardium, excised before and after CPB. Additionally, in eight of these patients ventricular specimens were investigated. The atrial Cx43 expression decreased during CPB, which was restricted to the VO group (p=0.008). In contrast, atrial Cx40 mRNA did not change during CPB. In ventricular myocardium compared to atrial mRNA levels, Cx40 was lower (p=0.006) and Cx43 higher (p=0.017) expressed, without significant change during CPB. This study revealed a significant influence of CPB and the underlying heart defect on Cx43 expression.     

Age-dependent mobilization of circulating endothelial progenitor cells in infants and young children undergoing cardiac surgery with cardiopulmonary bypass

This study was designed to find the effects of age on circulating endothelial progenitor cells (EPCs) and their mobilization in infants and young children following surgical correction of congenital heart defects. In 60 consecutive infants and young children (1 month to 3 years old) undergoing repair of atrial/ventricular septal defect, the numbers of EPCs and plasma levels of IL-6, -8, -10, TNF-α, VEGF and G-CSF were determined preoperatively, at the end of cardiopulmonary bypass (CPB), as well as 6, 12, 24, 48, 72 and 96 h following surgery. Preoperative EPCs were reduced with increased age, similar to changes in plasma VEGF and G-CSF levels. Rapid mobilizations of EPCs and plasma VEGF, G-CSF were induced by cardiac surgery with CPB in all infants and young children, and the increased volumes of EPCs, VEGF and G-CSF decreased with age decreasing. The increased volumes of IL-6, -8, -10 and TNF-α were similar in different age groups. However, mobilization of EPCs, plasma VEGF and G-CSF were limited in infants <6 months old, which did not correlate with change in inflammatory IL activation. Preoperative EPCs and plasma levels of VEGF and G-CSF were reduced with increasing age in infants and young children. Although a significant increase in EPCs and release of cytochemokines were observed in infants undergoing CPB, the mobilization of EPCs of the infants <6 months old are limited.     

Leptin and soluble leptin receptor changes after pulmonary endarterectomy: relations to cortisol and cytokine network

Leptin is a hormone that regulates food intake. During inflammatory status, leptin may contribute to the anorexia and cachexia of infection. Pulmonary endarterectomy was used as a model of non-infectious cytokine network hyperstimulation. Leptin and soluble leptin receptor (SLR) were compared with evolution of cortisol and inflammatory cytokines in twenty-two patients with chronic thromboembolic pulmonary hypertension treated with pulmonary endarterectomy using cardiopulmonary bypass (CBP) and deep hypothermic circulatory arrest (DHCA). Leptin, SLR, cortisol, IL-beta, IL-6, IL-8, and TNFalpha concentrations in arterial blood were measured before/after sternotomy, last DHCA, separation from bypass, 12, 18, 24, 36, and 48 h after sternotomy. Mean duration of CPB was 338.2 min.; mean circulatory arrest time 39.9 min. The initial decline of leptin, SLR, TNFalpha, IL-6, and IL-8 was followed by an increase culminating 6-24 h after sternotomy. Leptin peak levels were detected 24 h after sternotomy (28.0 ng/ml, 21.9-37.6). IL-6 culminated after separation from CPB, IL-8 was highest 12 h after sternotomy. Leptin concentrations correlated with IL-6 (r=0.82), and TNFalpha (r=0.73). Large cardiovascular surgery caused a significant increase in serum leptin, indicating its acute regulation by stress factors. This effect may be secondary to the inflammatory response mediated via cytokine stimulation. Correlation between leptin and IL-6 indicates the role of IL-6 in leptin induction.     

Oxidative stress precedes peak systemic inflammatory response in pediatric patients undergoing cardiopulmonary bypass operation

Oxidative stress seems to contribute to cardiopulmonary bypass (CPB)-related postoperative complications. Pediatric patients are particularly prone to these complications. With this in mind, we measured oxidative stress markers in blood plasma of 20 children undergoing elective heart surgery before, during, and up to 48 h after cessation of CPB, along with inflammatory parameters and full analysis of iron status. Ascorbate levels were decreased by approximately 50% (P < 0.001) at the time of aorta cross-clamp removal (or pump switch-off in 4 patients with partial CPB), and associated with corresponding increases in dehydroascorbate (P < 0.001, r = -0.80) and malondialdehyde (P < 0.01, r = -0.59). In contrast to the immediate oxidative response, peak levels of IL-6 and IL-8 were not observed until 3-12 h after CPB cessation. The early loss of ascorbate correlated with duration of CPB (P < 0.002, r = 0.72), plasma hemoglobin after cross-clamp removal (P < 0.001, r = 0.70), and IL-6 and IL-8 levels at 24 and 48 h after CPB (P < 0.01), but not with postoperative lactate levels, strongly suggesting that hemolysis, and not inflammation or ischemia, was the main cause of early oxidative stress. The correlation of ventilation time with early changes in ascorbate (P < 0.02, r = 0.55), plasma hemoglobin (P < 0.01, r = 0.60), and malondialdehyde (P < 0.02, r = 0.54) suggests that hemolysis-induced oxidative stress may be an underlying cause of CPB-associated pulmonary dysfunction. Optimization of surgical procedures or therapeutic intervention that minimize hemolysis (e.g., off-pump surgery) or the resultant oxidative stress (e.g., antioxidant treatment) should be considered as possible strategies to lower the rate of postoperative complications in pediatric CPB.     

The effect of methylprednisolone on cytokine concentration and leukocyte adhesion molecule expression in an isolated cardiopulmonary bypass system

This study examines the effect of methylprednisolone on cytokine balance and adhesion molecule expression within an isolated cardiopulmonary bypass (CPB) system. This isolated CPB system is an in vitro model which simulates the pro-inflammatory immune response. Whole blood from 10 volunteers was obtained in two equal amounts. Heparin and saline were added to the control group while heparin and methylprednisolone were added to the methylprednisolone group. The blood was added to two identical CPB circuits and bypass commenced by a trained perfusionist. Samples were taken at blood donation (Sample 0), 10 min after the addition of drugs (Sample 1) and after 30, 60 and 90 min of CPB (Samples 2, 3 and 4, respectively). Cytokines interleukin-8 (IL-8), interleukin-10 (IL-10), interleukin-1 receptor antagonist (IL-1ra) and tumour necrosis factor soluble receptor 2 (TNFsr2) and the leucocyte adhesion molecules L-selectin, HLA DR, CD18 and CD11b were determined. IL-8 increased in both groups. This increase was significantly less in the methylprednisolone group. Increases in granulocyte CD11b and CD18 expression were less in the methylprednisolone group than in the control group but did not reach statistical significance. These results indicate that methylprednisolone significantly reduces the production of IL-8 in an isolated CPB system. This effect occurs in the absence of IL-10.     

Transient Th1/Th2 disbalance indicates postoperative effusions and edema after cardiopulmonary bypass in children.

BACKGROUND: Cardiac surgery with cardiopulmonary bypass (CPB) induces substantial release of IL-10, indicating increased Th2 cell response. Therefore, in this study, we wanted to verify if this response is due to CPB or surgical trauma, and to study its relation to postoperative effusions and edema (POEE) in children. METHODS: Th1/Th2 reaction was monitored in children undergoing cardiovascular surgery with (n = 75) and without CPB (n = 29). RESULTS: Surgery with CPB compared to surgery without CPB induced a transient shift towards Th2. Elevated Th2 response was related to increased vascular permeability and POEE. CONCLUSION: The immune suppression/Th2 response is typical for CPB, and at intermediate level is tolerable but at high level could be adverse for the patients.     

Acute renal dysfunction after cardiac surgery with cardiopulmonary bypass is associated with plasmatic IL6 increase

Background: Acute renal dysfunction (ARD) is common after cardiac surgery with cardiopulmonary bypass (CPB). CPB results in a sudden systemic inflammatory response. Systemic and local pro-inflammatory cytokines synthesis has been linked with sub-clinical renal injury, especially tubular lesions. Therefore, we sought to assess the systemic synthesis pro-inflammatory cytokines and its association with perioperative ARD after cardiac surgery with CPB. Methods: Sixty-two patients undergoing cardiac surgery with CPB were prospectively included. Four groups of patients were defined according to blood creatinine increase: no ARD (less than 25% increase), faint ARD (25–50% increase), moderate ARD (50–100% increase), severe ARD (more than 100% increase). Results: Within the 48 post-operative hours was ARD observed as no dysfunction (41.9%), faint (32.2%), moderate (16.1%), severe (9.6%). One patient had to undergo a dialysis. Pre-operative characteristics were homogenous between the four groups excepted the left ventricle ejection fraction. ARD was associated with a low urinary output with high sodium excretion fraction. Significant increase of IL-6 level occurred when patients underwent a severe ARD despite no significant differences for the CRP and TNF-α concentrations. Conclusion: Severe acute renal dysfunction after cardiac surgery with CPB is associated with a significant increased IL-6 systemic production.     

Perioperative kinetics of endocan in patients undergoing cardiac surgery with and without cardiopulmonary bypass

IntroductionEndothelial Specific Molecule-1 or endocan is a novel biomarker associated with the development of acute lung injury (ALI) in response to a systemic inflammatory state such as trauma. Acute Respiratory Distress syndrome (ARDS), a severe form of ALI is a devastating complication that can occur following cardiac surgery due to risk factors such as the use of cardiopulmonary bypass (CPB) during surgery. In this study we examine the kinetics of endocan in the perioperative period in cardiac surgical patients.MethodsAfter ethics approval, we obtained informed consent from 21 patients undergoing elective cardiac surgery (3 groups with seven patients in each group: coronary artery bypass grafting (CABG) with the use of CPB, off-pump CABG and complex cardiac surgery). Serial blood samples for endocan levels were taken in the perioperative period (T0: baseline prior to induction, T1: at the time of heparin administration, T2: at the time of protamine, T2, T3, T4 and T5 at 1, 2, 4 and 6 h following protamine administration respectively). Endocan samples were analysed using the enzyme-linked immunosorbent assay (ELISA) method. Statistical analysis incorporated the use of test for normality.ResultsOur results reveal that an initial rise in the levels of serum endocan from baseline in all patients after induction of anaesthesia. Patients undergoing off-pump surgery have lower endocan concentrations in the perioperative period than those undergoing CPB. Endocan levels decrease following separation from CPB, which may be attributed to haemodilution following CPB. Following administration of protamine, endocan concentrations steadily increased in all patients, reaching a steady state between 2 and 6 h. The baseline endocan concentrations were elevated in patients with hypertension and severe coronary artery disease.ConclusionBaseline endocan concentrations are higher in hypertensive patients with critical coronary artery stenosis. Endocan concentrations increased after induction of anaesthesia and decreased four hours after separation from CPB. Systemic inflammation may be responsible for the rise in endocan levels following CPB.     

乌司他丁对心肺转流下心脏手术患者炎症因子及认知功能的影响

目的:探索乌司他丁(UTI)对心肺转流(CPB)下心脏手术患者炎症因子及认知功能的影响。方法:选择自2010年5月至2014年9月我院收治的CPB瓣膜置换手术患者60例,按照随机数表法将患者分成对照组和观察组,每组30例。观察组患者在麻醉诱导后静脉泵入1.2×10~4U/kg UTI,在CPB结束前5 min从体外管道内给予0.6×10~4U/kg UTI,对照组患者给予等量的生理盐水。对比两组CPB前(T0)、CPB开始后1 h(T1)、CPB结束后1 h(T2)、术后4 h(T3)及术后24 h(T4)的血浆肿瘤坏死因子-α(TNF-α)、白细胞介素-6/10(IL-6/10)、中性粒细胞弹性蛋白酶(NE)、星形胶质细胞S100蛋白的β亚型(S100β)、超氧化物歧化酶(SOD)和丙二醛(MDA),在术前1 d和术后7 d时,采用简易精神状态检查表(MMSE)对患者进行神经精神功能测试,并评价患者的术后认知功能障碍(POCD)的发生率。结果:与T0相比,两组患者T1-T4的TNF-α、IL-6、NE、S100β、MDA水平明显升高,且观察组显著低于对照组,而两组IL-10、SOD水平显著下降,观察组显著高于对照组(P0.05)。术后7d,两组患者MMSE评分均明显高于术前1 d,且观察组显著高于对照组(P0.05);观察组POCD的发生率明显低于对照组(P0.05)。结论:UTI可以有效降低CPB下行瓣膜置换术患者的炎症因子水平,并改善患者的POCD,对于临床用药具有指导意义。     

Interleukin 8 (IL-8) in the bronchoalveolar lavage fluid from patients with the adult respiratory distress syndrome (ARDS) and patients at risk for ARDS.

A sensitive and specific radioimmunoassay was used to measure interleukin 8 (IL-8) in bronchoalveolar lavage fluids from control subjects, patients with the adult respiratory distress syndrome (ARDS) and patients undergoing coronary bypass surgery, a risk factor for developing ARDS. Concentrations of IL-8, albumin, total protein and numbers of neutrophils were higher in both patient groups than in controls. Levels of IL-8 were significantly correlated with the influx of neutrophils, plasma protein extravasation and with the PaO2/FiO2 ratio. These data suggest that IL-8 may mediate the recruitment of neutrophils from the vascular compartment into the alveolar space and may therefore be an important determinant in neutrophil-mediated lung injury. Since increased levels of IL-8 were also found in BAL fluid from patients at risk in whom ARDS did not develop, other factors are likely to be involved and IL-8, as well as other markers of inflammation, are of little prognostic use.     

Evaluation of cytokine expression by blood monocytes of lactating Holstein cows with or without postpartum uterine disease

Whereas neutrophils are the main phagocytic leukocytes, monocytes and macrophages are actively involved in immunomodulation after infection. Recent studies have demonstrated that neutrophil function is impaired by the state of negative energy balance around parturition, and that cows that develop uterine disease have a greater degree of negative energy balance than healthy cows. The objectives of this study were to compare monocyte gene expression and protein secretion of selected cytokines from calving to 42 d after calving in Holstein cows that did or did not develop uterine disease. Real time quantitative RT-PCR (Tumor necrosis factor-α (TNFα), Interleukin (IL)-1β, IL-6, IL-8 and IL-10) and ELISA (TNFα, IL-1β and IL-8) were used to evaluate cytokine response following in vitro stimulation of blood-derived monocytes with irradiated E. coli. Relative to unstimulated cells, E. coli-stimulated monocytes from cows with metritis had lower gene expression of key pro-inflammatory cytokines than healthy cows from calving to 14 d after calving (TNFα at 0, 7, and 14 d after calving, IL-1β and IL-6 at 7 and 14 d after calving; P < 0.05). There were no significant differences between groups for expression of IL-8 or the anti-inflammatory cytokine IL-10. This was due, in part, to higher gene expression in unstimulated monocytes (TNFα, IL-1β, IL-6 and IL-10) in early lactation from cows with metritis. Expression of mRNA in stimulated cells (relative to housekeeping genes) was lower for TNFα (7 and 14 d postpartum) and for IL-10 (7 and 14 d postpartum) in cows with metritis. Concentration of TNFα was lower in the culture medium of E. coli-stimulated monocytes from cows with metritis than healthy cows at calving and 7 and 21 d after calving (P < 0.05). Circulating cytokine concentrations were not different between groups for IL-8 and were below the limits of detection for TNFα and IL-1β. Cytokine gene expression and production were similar between healthy cows and cows that developed endometritis, diagnosed cytologically at 42 d after calving. We concluded that altered levels of expression and production of pro-inflammatory cytokines postpartum could contribute to impaired inflammatory response and predispose cows to development of metritis.     

Risk stratification in neonates and infants submitted to cardiac surgery with cardiopulmonary bypass: a multimarker approach combining inflammatory mediators, N-terminal pro-B-type natriuretic peptide and troponin I

Low cardiac output syndrome (LCOS) is a common problem following cardiac surgery with cardiopulmonary bypass (CPB) in neonates and infants, and its early recognition remains a challenging task. We aimed to test whether a multimarker approach combining inflammatory and cardiac markers provides complementary information for prediction of LCOS and death in children submitted to cardiac surgery with CPB. Forty-six children younger than 18 months with congenital heart defects were prospectively enrolled. No intervention was made. Blood samples were collected pre-operatively, during CPB and post-operatively (PO) for measurement of interleukin (IL)-6, IL-8, IL-10, tumor necrosis factor (TNF)-α, cardiac troponin I (cTnI) and N-terminal pro-B-type natriuretic peptide (NT-proBNP). Clinical data and outcome variables were recorded. Logistic regression was used to identify predictors of LCOS and death. Multivariate logistic regression identified pre-operative NT-proBNP and IL-8 4 h PO as independent predictors of LCOS, while cTnI 4 h PO and CPB length were independent predictors of death. The use of inflammatory and cardiac markers in combination improved sensitivity, negative predictive value and accuracy of the models. In conclusion, the combined assessment of inflammatory and cardiac biochemical markers can be useful for identifying young children at increased risk for LCOS and death after heart surgery with CPB.