Protective role of normothermic, hyperthermic and estrogen preconditioning and pretreatment on tumour necrosis factor-alpha-induced damage

BACKGROUND:

Tumour necrosis factor-alpha (TNF-α) has been reported to play an important role in ischemia reperfusion injury and ischemic preconditioning (IPC). However, its role is not completely understood. Recently, normothermic IPC (NIPC), hyperthermic IPC (HIPC), preconditioning (PC) with 17-beta estradiol (estrogen, E2) and E2 pretreatment were proven to be effective in reducing ischemia reperfusion injury.

OBJECTIVES:

To investigate the detrimental effects of TNF-α on the heart, and the protective effects of NIPC, HIPC, E2 PC and pretreatment on TNF-α-induced injury.

METHODS:

A Langendorff-perfused rat heart model was used for the present study. Hearts isolated from male rats were studied under eight different conditions (n=5 each): negative control; control treated with TNF-α without any further treatment; NIPC (preconditioned at 37°C); HIPC (preconditioned at 42°C); E2 PC; E2 pretreatment; normal, untreated hearts plus E2; or pretreated hearts perfused for 60 min with TNF-α and an E2-containing buffer.

RESULTS:

TNF-α treatment resulted in deterioration of heart function. HIPC offered better protection by significantly increasing left ventricular developed pressure (Pmax) and coronary flow (P<0.01), and by decreasing left ventricular end-diastolic pressure (P<0.01). NIPC or pretreatment of the hearts with E2 normalized left ventricular end-diastolic pressure, coronary flow and coronary vascular resistance (P<0.001); however, it did not normalize Pmax. The combination of E2 and HIPC did not show any synergetic protection; however, the addition of HIPC normalized Pmax (P<0.001).

CONCLUSIONS:

TNF-α treatment resulted in deterioration of heart hemodynamics, which were reversed by HIPC, E2 PC and pretreatment. The combination of these treatments did not add to the previously observed protection compared with when they were used individually.     

Neutrophil gelatinase-associated lipocalin as a biomarker for acute kidney injury in patients undergoing coronary artery bypass grafting

BACKGROUND/OBJECTIVE:

The development of acute renal injury (ARI) is an important indicator of clinical outcomes after cardiac surgery. Neutrophil gelatinase-associated lipocalin (NGAL) has been certified as a predictive biomarker of hypoxic ARI. The present study aimed to determine the predictive role of NGAL in coronary bypass graft (CABG) surgery.

METHOD:

A total of 72 consecutive patients undergoing elective CABG were enrolled in the study. NGAL levels were determined preoperatively and postoperatively after 6 h, 24 h and 72 h for all participants. The participants were then divided into two groups according to their preoperative creatinine levels (group I, creatinine 111.38 μmol/L to 361.55 μmol/L; group II, creatinine <111.38 μmol/L).

RESULTS:

There was no statistically significant difference between the groups according to their NGAL values (P>0.05), except at 6 h (P=0.045). Three patients required continuous hemodialysis. Comparison of the NGAL levels of these three patients with those of the other participants did not reveal any correlation with serum creatinine levels. In contrast, the NGAL levels were significantly lower in the continuous hemodialysis patients (1.9±1 ng/mL) compared with those of the other participants (22.6±12.8 ng/mL; P=0.001).

CONCLUSION:

NGAL is one of the most frequently used biomarkers for ARI after cardiac operations, especially in younger patients. The participants in the present study were coronary artery disease patients and were, therefore, older than patients in previous reports. These results support the view that NGAL is not a relevant predictive factor for ARI in patients with CABG, including older patients.     

High sensitivity C-reactive protein, tumor necrosis factor-α, interleukin-6, and vascular cell adhesion molecule-1 levels in Asian Indians with metabolic syndrome and insulin resistance (CURES-105)

Aim

The aim of this study was to assess levels of high-sensitivity C-reactive protein (hs-CRP), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and vascular cell adhesion molecule-1 (VCAM-1) in South Indian subjects with and without MS and among MS subjects with and without insulin resistance (IR).

Methodology

From the population-based Chennai Urban Rural Epidemiology Study, 334 subjects with MS and 342 subjects without MS were selected. Metabolic syndrome was diagnosed based on modified National Cholesterol Education Program criteria. High-sensitivity C-reactive protein, TNF-α, IL-6, and VCAM-1 were measured by enzyme-linked immunosorbent assay. Insulin resistance was calculated using the homeostasis model assessment (HOMA-IR) using the following formula: fasting insulin (µIU/ml) × fasting glucose (mmol/liter)/22.5.

Results

Subjects with MS had significantly higher levels of all four inflammatory markers compared to those without MS: hs-CRP (2.57 vs 2.19 mg/liter) (p < .05), TNF-α (4.47 vs 3.89 pg/ml) (p < .05), IL-6 (16.22 vs 10.96 pg/ml) (p < .05), and VCAM-1 (13.8 vs 7.94 pg/ml) (p < .05). In the total study subjects, hs-CRP (r = 0.089, p = .047), TNF-α (r = 0.113, p = .040), IL-6 (r = 0.176, p = .042), and VCAM-1 (r = 0.230, p = .06) were significantly correlated with MS. With increasing quartiles of IR, mean levels of hs-CRP (p for trend <.001) and TNF-α (p for trend <.05) increased linearly. MS subjects with IR had higher levels of hs-CRP (p < .001) and TNF-α (p < .05) compared to MS subjects without IR.

Conclusion

In Asian Indians, inflammatory cytokines hs-CRP, TNF-α, IL-6, and VCAM-1 are elevated in subjects with MS while hs-CRP and TNF-α are further elevated in those with MS and IR.     

Intermittent hypoxia-induced rat pancreatic β-cell apoptosis and protective effects of antioxidant intervention

Purpose:

Obstructive sleep apnea hypopnea syndrome (OSAHS), a common sleep and breathing disorder, is independently associated with metabolic dysfunction, including impaired glucose tolerance and insulin resistance. Intermittent hypoxia (IH), a pathological component of OSAHS, increases oxidative stress damage to pancreatic β-cells in animal models resembling patients with OSAHS. However, the precise mechanisms of IH-induced pancreatic β-cell dysfunction are not fully understood. In the present study, we established a mice model to investigate the underlying mechanisms of oxidative stress in IH-induced pancreatic β-cell apoptosis through antioxidant N-acetylcysteine (NAC) pretreatment.

Methods:

Twenty-four Wistar rats were randomly divided into four experimental groups: normal control group, intermittent normoxia group, IH group and antioxidant intervention group. Pancreatic β-cell apoptosis rates were detected by terminal deoxynucleotidyl transferase-mediated dUTP-nick end-labeling; Bcl-2 and Bax protein expressions were detected by immunohistochemistry staining and western blotting.

Results:

In our study, we demonstrated that IH exposure causes an increased activation of pancreatic β-cell apoptosis compared with that in the normal control group and intermittent normoxia group, accompanied by the downregulation of Bcl-2 and upregulation of Bax (P<0.05). Furthermore, compared with the IH group, antioxidant (NAC) pretreatment significantly decreased IH-mediated β-cell apoptosis and reversed the ratio of Bcl-2/Bax expression (P<0.05).

Conclusion:

Taken together, these results demonstrate a critical role of oxidative stress in the regulation of apoptosis through Bcl-2 and Bax signaling. The antioxidant NAC has a protective effect against IH-induced pancreatic β-cell apoptosis.     

Cardioprotective effects of Guanxinshutong (GXST) against myocardial ischemia/ reperfusion injury in rats

Background The protective effects against reperfusion injury of cardioprotective drugs have recently been evaluated and found to be inadequate. Guanxinshutong (GXST), a combination of the traditional herb and Mongolian medicine, is effective and safe in treating angina pectoris in clinical trials. We assess the cardioprotective effects of GXST against myocardial ischemia and reperfusion (MI/R) injury in rats and explore its possible mechanism. Methods Forty-five male Sprague Dawley rats were randomized into three groups: non-MI/R group (Sham, n = 15), MI/R group treated with vehicle (Control, n = 15) and MI/R group treated with GXST (Drug, n = 15). MI/R was induced by ligation of the left anterior descending coronary artery (LAD) for 30 minutes, followed by 2/24 hour reperfusion in the Control and Drug groups. In the Sham group, the LAD was exposed without occlusion. GXST powder (in the Drug group) or saline (in the Control and Sham groups) were administered via direct gastric gavage from 7 day prior to surgery. Blood samples were collected from the carotid artery (10 rats each group) after 2 hours of reperfusion, to determine the levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6) and intercellular adhesion molecule-1 (ICAM-1) using enzyme-linked immunosorbent assays. The animals were then sacrificed and the hearts were harvested for histopathology and western blot analysis. Infarct size was measured in the remaining five rats in each group after 24 hours reperfusion. Results GXST significantly decreased levels of TNF-α, IL-1β, IL-6, ICAM-1, apoptosis index (AI) and infarct size. GXST also obviously inhibited nuclear factor kappa B (NF-κB) activity when compared with the Control group (all P < 0.05). Conclusions GXST is effective in protecting the myocardium against MI/R injury in rats. Its possible cardioprotective mechanism involves inhibition of the inflammatory response and apoptosis following MI/R injury.     

High Serum Levels of TGF-β in Iranians With Chronic HBV Infection

Background

The transforming growth factor-β (TGF-β) is an important cytokine with anti-inflammatory properties.

Objectives

The main purpose of this study was to compare the serum levels of TGF-β in a group of chronic HBV infected (CHB) patients as well as healthy individuals from South-East of Iran.

Patients and Methods

Sixty patients with CHB as well as sixty healthy individuals were enrolled in the study. ELISA technique was applied to measure the serum levels of TGF-β in both groups.

Results

Our results revealed that the serum levels of TGF-β were significantly increased in CHB patients in compare to healthy controls.

Conclusions

According to this result, it may be concluded that high serum levels of TGF-β may be a mechanism by which immune response against HBV is suppressed.     

A Disintegrin and Metalloprotease with Thrombospondin Motif 2 May Contribute to Cirrhosis in Humans through the Transforming Growth Factor-β/SMAD Pathway

Background/Aims

We aimed to investigate the correlation between a disintegrin and metalloprotease with thrombospondin motif 2 (ADAMTS-2) and transforming growth factor-β1 (TGF-β1) in clinical human cirrhotic tissues.

Methods

The liver tissues of 24 patients (16 cases with cirrhotic portal hypertension as the cirrhosis group and eight cases with healthy livers as the normal group) were collected. Immunohistochemistry and Western blots were performed to evaluate the protein expression levels of ADAMTS-2 and TGF-β1. Western blots for other key mediators of cirrhotic progression, including SMAD2, SMAD3, TGF-β receptor II (TGFβRII), matrix metalloproteinases 2 (MMP2), and tissue inhibitor of matrix metalloproteinases 2 (TIMP2), were also performed.

Results

Cirrhotic tissues showed higher percentages of collagen. The protein expression levels of ADAMTS-2 and TGF-β1 were significantly higher in the cirrhotic group as compared to the matched normal group (p<0.05), and there was a positive correlation between these two proteins (r=0.862, p<0.01). The protein expressions of MMP2, TIMP2, and TGFβRII, as well as the phosphorylated forms of SMAD2 and SMAD3, were significant higher in the cirrhotic group (p<0.01 or p<0.05).

Conclusions

These findings suggested that ADAMTS-2 and TGF-β1 may play important roles in the pathogenesis of human cirrhosis; specifically, TGF-β1 may induce the expression of ADAMTS-2 through the TGFβ/SMAD pathway.     

The Effect of Intestinal Permeability and Endotoxemia on the Prognosis of Acute Pancreatitis

Background/Aims

Early intestinal mucosal damage plays an important role in severe acute pancreatitis (AP). Previous studies have shown that intestinal permeability (IP), serum endotoxin and cytokines contribute to the early intestinal barrier dysfunction in AP. This study explored the predictive capacity of IP, endotoxemia and cytokines as prognostic indicators in AP patients.

Methods

Eighty-seven AP patients were included in the study. The patients were classified into three groups according to the Balthazar computed tomography severity index (CTSI). We compared the biochemical parameters, including IP, serum endotoxin level and cytokine level among the three groups. The associations of IP with serum endotoxin, cytokines, CTSI, and other widely used biochemical parameters and scoring systems were also examined.

Results

IP, serum endotoxin, interleukin (IL-6) and tumor necrosis factor (TNF)-α had a positive correlation with the CTSI of AP. Endotoxin, IL-6, TNF-α, CTSI, the Ranson/APACHE II score, the duration of hospital stay, complications and death significantly affect IP in the AP patients.

Conclusions

We believe that IP with subsidiary measurements of serum endotoxin, IL-6 and TNF-α may be reliable markers for predicting the prognosis of AP. Further studies that can restore and preserve gut barrier function in AP patients are warranted.     

Role of tumour necrosis factor-alpha and other cytokines in ischemia-reperfusion-induced injury in the heart

BACKGROUND:

Several investigations have implicated cytokines such as tumour necrosis factor-alpha (TNF-α), interleukin (IL)-1, IL-6, IL-8 and transforming growth factor-beta in the pathophysiology of cellular dysfunction in ischemia-reperfusion (I/R). Although an increase in the production of these cytokines has been detected after myocardial infarction and cardiopulmonary bypass surgery, their exact role and mechanisms for inducing cardiac dysfunction are poorly understood.

OBSERVATIONS:

TNF-α, transforming growth factor-beta, IL-1, IL-6 and IL-8 have frequently been studied in different cardiovascular diseases, including I/R injury in the heart. Low concentrations of TNF-α appear to exert cardioprotective effects, whereas high concentrations have been shown to produce deleterious actions in the heart. Some efforts have been made to explore the molecular mechanisms of cytokine actions; however, such information is insufficient to develop therapeutic strategies to combat their deleterious effects during the development of I/R injury in the heart.

CONCLUSIONS:

In addition to a time-dependent response, the conflicting effects of cytokines seem to depend on their concentrations used in different experimental studies. It is also likely that both the beneficial and pathophysiological actions of cytokines occur concomitantly. On the basis of the existing literature, it is suggested that different ways need to be found to modify the synthesis as well as the cardiodepressant actions of cytokines to improve the therapy of ischemic heart disease.     

Mid-term outcomes of off-pump versus on-pump coronary artery bypass graft surgery

OBJECTIVE:

To evaluate survival and readmissions to hospital for cardiac events or coronary revascularization (REVASC) in patients having off-pump (OPCAB) versus conventional on-pump (CCAB) coronary artery bypass graft surgery (CABG).

METHODS:

Of 11,368 consecutive patients undergoing isolated CABG between 1996 and 2002, 514 had OPCAB surgery. Using propensity scores, 503 CCAB patients were randomly matched to 503 OPCAB patients.

RESULTS:

There were no clinical or statistical differences between the two groups for any prognostic variable. However, OPCAB patients received significantly fewer distal anastomoses than the CCAB group (2.6±1.0 versus 3.1±1.0; P<0.001). There was no difference in operative mortality (OPCAB 1.0%, CCAB 1.4%; P=0.6), but the OPCAB group had significantly fewer operative strokes (0.2% versus 1.8%; P=0.01). Follow-up was 99.7% complete at 2.2±1.2 years (range 0 to 6 years). Twice as many OPCAB patients (n=24) required REVASC compared with the CCAB (n=11) group. The following five-year actuarial outcomes are presented for CCAB and OPCAB, respectively: survival: 77±6%, 76±8%, P=0.8; freedom from REVASC: 95±3%, 92±2%, P=0.02; and cardiac event-free survival: 76±5%, 62±8%; P=0.05. Cox regression revealed that OPCAB was a significant independent predictor of poorer freedom from REVASC (RR 2.2, 95% CI 1.0 to 4.6; P=0.04) and cardiac event-free survival (RR 1.6, 95%CI 1.1 to 2.2; P=0.02).

CONCLUSIONS:

The use of OPCAB remains controversial. These results, from this early experience, suggest that despite improved hospital outcomes, the lesser degree of REVASC raises concerns about the need for repeat revascularization in the OPCAB group.     

Comparison of liver regeneration after a splenectomy and splenic artery ligation in a dimethylnitrosamine-induced cirrhotic rat model

Aim:

A splenectomy and splenic artery ligation accelerate liver regeneration and improve liver function after a hepatectomy. However, there are no studies that directly compared the effects of a splenectomy and splenic artery ligation. In the present study, we compared the effects of a splenectomy and splenic artery ligation in cirrhotic rats.

Methods:

Dimethylnitrosamine (DMN) was administered intraperitoneally for 4 weeks to induce cirrhosis. The rats were divided into three groups: sham operation (CT group), splenic artery ligation (SAL group) and splenectomy (SP group). Liver functions [alanine aminotransferase (ALT) and total bilirubin (T. Bil)], plasma TGF-β1, histopathological changes, extent of liver fibrosis (fibrotic rate) and regeneration [Ki-67 labelling index(LI)] were investigated in each group.

Results:

ALT and T. Bil levels were significantly lower in the SP group than the CT and SAL groups. TGF-β1 levels were significantly lower in the SP group than in the CT and SAL groups. The fibrotic rate was significantly lower in the SP group than in the CT and SAL groups. The Ki-67 labelling index was significantly higher in the SP group than in the CT and SAL groups.

Discussion:

A Splenectomy significantly improved liver regeneration with reduction of plasma TGF-β1 levels compared with splenic artery ligation in DMN-treated cirrhotic rats.     

Inflammation and oxidative stress caused by nitric oxide synthase uncoupling might lead to left ventricular diastolic and systolic dysfunction in patients with hypertension

Objective To investigated the role of oxidative stress, inflammation, hypercoagulability and neuroendocrine activation in the transition of hypertensive heart disease to heart failure with preserved ejection fraction (HFPEF). Methods We performed echocardiography for 112 patients (≥ 60 years old) with normal EF (18 controls and 94 with hypertension), and determined protein carbonylation (PC), and tetrahydrobiopterin (BH4), C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), fibrinogen, plasminogen activator inhibitor type-I (PAI-I), von Willebrand factor, chromogranin A (cGA) and B-type natriuretic peptide (BNP) levels from their blood samples. Results We found that 40% (38/94) of the patients with hypertension (HT) had no diastolic dysfunction (HTDD-), and 60% (56/94) had diastolic dysfunction (HTDD+). Compared to the controls, both patient groups had increased PC and BH4, TNF-α, PAI-I and BNP levels, while the HTDD+ group had elevated cGA and CRP levels. Decreased atrial and longitudinal left ventricular (LV) systolic and diastolic myocardial deformation (strain and strain rate) was demonstrated in both patient groups versus the control. Patients whose LV diastolic function deteriorated during the follow-up had elevated PC and IL-6 level compared to their own baseline values, and to the respective values of patients whose LV diastolic function remained unchanged. Oxidative stress, inflammation, BNP and PAI-I levels inversely correlated with LV systolic, diastolic and atrial function. Conclusions In patients with HT and normal EF, the most common HFPEF precursor condition, oxidative stress and inflammation may be responsible for LV systolic, diastolic and atrial dysfunction, which are important determinants of the transition of HT to HFPEF.     

The importance of depression and alcohol use in coronary artery bypass graft surgery patients: risk factors for delirium and poorer quality of life

Objective To investigate whether depression, anxiety and stress increase the risk for delirium and poor quality of life (QOL) after coronary artery bypass (CABG) surgery. Methods A total of 180 CABG patients (mean age of 63.5 ± 10.1 years, 82.2% males) completed baseline and postoperative self-report questionnaires to assess distress and QOL. Incident delirium was diagnosed postoperatively with a structured clinical interview and patients were monitored every day post-operatively for confusion and disturbance in consciousness. Results Delirium developed in 63 persons (35% of sample). After adjustment for covariates, delirium was significantly associated with depression [odds ratio (OR): 1.08; 95% confidence interval (CI): 1.03–1.13, P = 0.003], anxiety (OR: 1.07; 95% CI: 1.02–1.13, P = 0.01) and stress (OR: 1.05; 95% CI: 1.00–1.09, P = 0.03). Preoperative depression scores were associated with poorer QOL including bodily pain (β = -0.39, P = 0.013), vitality (β=-0.32, P = 0.020), social functioning (β = -0.51, P ≤ 0.001), emotional role function (β = -0.44, P = 0.003) and general health (β = -0.33, P = 0.038). Among the covariates, harmful levels of alcohol use was consistently associated with poorer QOL. Conclusions Depression and harmful levels of alcohol use were consistently associated with poorer QOL whereas depression, anxiety and stress were associated with delirium risk. These findings point to further research examining depression and harmful levels of alcohol use in coronary heart disease populations undergoing coronary revascularization.     

In Vitro Analysis of CsA-Induced Hepatotoxicity in HepG2 Cell Line: Oxidative Stress and α2 and β1 Integrin Subunits Expression

Background

Cyclosporine A (CsA)-induced hepatotoxicity could be due to a reduction in α2β1 integrin expression that may either be from the direct effect of CsA itself or from reactive oxygen species (ROS) overproduction.

Objectives

In this study we aimed to identify the cellular mechanisms underlying CsA-induced hepatic injury by investigating the activation patterns of the antioxidant enzymes, using HepG2 as an in vitro model.

Materials and Methods

HepG2 cells were cultured with different concentrations of CsA (0, 0.1, 1, 10 μg/ml) for 72 h. Effect of CsA on, 1) cellular integrity, 2) glutathione reductase (GR) and glutathione peroxidase (GPx) activity, 3) cellular levels of glutathione (GSH), 4) intracellular ROS, 5) ALT and AST activities, 6) urea production and 7) α2β1 integrin expression were assayed.

Results

CsA treatment demonstrated a dose dependent increase in intracellular levels of ROS, GPx activity and decrease in GSH levels (P<0.05). GR activity was mildly attenuated in 1 and 10 µg/ml concentrations of CsA. Alanine aminotranferase (ALT) and aspartate aminotransferase (AST) levels increased in CsA treated cells, while urea synthesis was significantly decreased following treatment with higher concentrations of CsA (P<0.05). Significant down-regulation of β1integrin expression was observed in 1 and 10 µg/ml CsA treated cells while α2 integrin mRNA was significantly down-regulated in all CsA treated cells.

Conclusions

The observed reduction of α2β1 integrin expression following CsA treatment could be proposed as a possible pathway of CsA-induced hepatotoxicity. Further studies are required to elucidate whether this attenuated expression is due to the direct effect of CsA or caused by overproduction of ROS.     

Cardiac Home Education and Support Trial (CHEST): A pilot study

BACKGROUND:

Coronary artery bypass graft (CABG) surgery is performed more frequently in individuals who are older and sicker than in previous years. Increased patient acuity and reduced hospital length of stays leave individuals ill prepared for their recovery.

OBJECTIVES:

To test the feasibility of a peer support program and determine indicators of the effects of peer support on recovery outcomes of individuals following CABG surgery.

METHODS AND RESULTS:

A pre-post test pilot randomized clinical trial design enrolled men and women undergoing first-time nonemergency CABG surgery at a single site in Ontario. Patients were randomly assigned to either usual care or peer support. Patients allocated to usual care (n=50) received standard preoperative and postoperative education. Patients in the peer support group (n=45) received individualized education and support via telephone from trained cardiac surgery peer volunteers for eight weeks following hospital discharge. Most (93%) peer volunteers believed they were prepared for their role, with 98% of peer volunteers initiating calls within 72 h of the patient’s discharge. Peer volunteers made an average of 12 calls, less than 30 min in duration over the eight-week recovery period. Patients were satisfied with their peer support (n=45, 98%). The intervention group reported statistical trends toward improved physical function (physical component score) (t [89]=−1.6; P=0.12) role function (t [93]=−1.9; P=0.06), less pain (t [93]=1.30; P=0.20) and improved cardiac rehabilitation enrollment (χ²=2.50, P=0.11).

CONCLUSIONS:

These preliminary results suggest that peer support may improve recovery outcomes following CABG. Data from the present pilot trial also indicate that a home-based peer support intervention is feasible and an adequately powered trial should be conducted.     

Contribution of damage-associated molecular patterns to transfusion-related acute lung injury in cardiac surgery

Background

The incidence of transfusion-related acute lung injury (TRALI) in cardiac surgery patients is high and this condition contributes to an adverse outcome. Damage-associated molecular pattern (DAMP) molecules, HMGB1 and S100A12, are thought to mediate inflammatory changes in acute respiratory distress syndrome. We aimed to determine whether DAMP are involved in the pathogenesis of TRALI in cardiac surgery patients.

Materials and methods

This was a secondary analysis of a prospective observational trial in cardiac surgery patients admitted to the Intensive Care Unit of a university hospital in the Netherlands. Fourteen TRALI cases were randomly matched with 32 transfused and non-transfused controls. Pulmonary levels of HMGB1, S100A12 and inflammatory cytokines (interleukins-1β, -6, and -8 and tumour necrosis factor-α) were determined when TRALI evolved. In addition, systemic and pulmonary levels of soluble receptor for advanced glycation end products (sRAGE) were determined.

Results

HMGB1 expression and levels of sRAGE in TRALI patients did not differ from those in controls. There was a trend towards higher S100A12 levels in TRALI patients compared to the controls. Furthermore, S100A12 levels were associated with increased levels of markers of pulmonary inflammation, prolonged cardiopulmonary bypass, hypoxemia and duration of mechanical ventilation.

Conclusion

No evidence was found that HMGB1 and sRAGE contribute to the development of TRALI. S100A12 is associated with duration of cardiopulmonary bypass, pulmonary inflammation, hypoxia and prolonged mechanical ventilation and may contribute to acute lung injury in cardiac surgery patients.     

Applicability of Two International Risk Scores in Cardiac Surgery in a Reference Center in Brazil

Background

The applicability of international risk scores in heart surgery (HS) is not well defined in centers outside of North America and Europe.

Objective

To evaluate the capacity of the Parsonnet Bernstein 2000 (BP) and EuroSCORE (ES) in predicting in-hospital mortality (IHM) in patients undergoing HS at a reference hospital in Brazil and to identify risk predictors (RP).

Methods

Retrospective cohort study of 1,065 patients, with 60.3% patients underwent coronary artery bypass grafting (CABG), 32.7%, valve surgery and 7.0%, CABG combined with valve surgery. Additive and logistic scores models, the area under the ROC (Receiver Operating Characteristic) curve (AUC) and the standardized mortality ratio (SMR) were calculated. Multivariate logistic regression was performed to identify the RP.

Results

Overall mortality was 7.8%. The baseline characteristics of the patients were significantly different in relation to BP and ES. AUCs of the logistic and additive BP were 0.72 (95% CI, from 0.66 to 0.78 p = 0.74), and of ES they were 0.73 (95% CI; 0.67 to 0.79 p = 0.80). The calculation of the SMR in BP was 1.59 (95% CI; 1.27 to 1.99) and in ES, 1.43 (95% CI; 1.14 to 1.79). Seven RP of IHM were identified: age, serum creatinine > 2.26 mg/dL, active endocarditis, systolic pulmonary arterial pressure > 60 mmHg, one or more previous HS, CABG combined with valve surgery and diabetes mellitus.

Conclusion

Local scores, based on the real situation of local populations, must be developed for better assessment of risk in cardiac surgery.     

Protective effect of heme oxygenase-1 on Wistar rats with heart failure through the inhibition of inflammation and amelioration of intestinal microcirculation

Background Myocardial infarction (MI) has likely contributed to the increased prevalence of heart failure (HF). As a result of reduced cardiac function, splanchnic blood flow decreases, causing ischemia in villi and damage to the intestinal barrier. The induction of heme oxygenase-1 (HO-1) could prevent, or lessen the effects of stress and inflammation. Thus, the effect and mechanism thereof of HO-1 on the intestines of rats with HF was investigated. Methods Male Wistar rats with heart failure through ligation of the left coronary artery were identified with an left ventricular ejection fraction (LvEF) of < 45% through echocardiography and then divided into various experimental groups based on the type of peritoneal injection they received [MI: saline; MI + Cobalt protoporphyrin (CoPP): CoPP solution; and MI + Tin mesoporphyrin IX dichloride (SnMP): SnMP solution]. The control group was comprised of rats without coronary ligation. Echocardiography was performed before ligation for a baseline and eight weeks after ligation in order to evaluate the cardiac function of the rats. The bacterial translocation (BT) incidence, mesenteric microcirculation, amount of endotoxins (ET) in the vein serum, ileum levels of HO-1, carbon oxide (CO), nitric oxide (NO), interleukin (IL)-10, tumour necrosis factor-α (TNF-α), and the ileum morphology were determined eight weeks after the operation. Results The rats receiving MI + CoPP injections exhibited a recovery in cardiac function, an amelioration of mesenteric microcirculation and change in morphology, a lower BT incidence, a reduction in serum and ileac NO and TNF-α levels, and an elevation in ileac HO-1, CO, and interleukin-10 (IL-10) levels compared to the MI (P < 0.05) group. The rats that received the MI + SnMP injections exhibited results inverse to the MI (P < 0.05) group. Conclusions HO-1 exerted a protective effect on the intestines of rats with HF by inhibiting the inflammation and amelioration of microcirculation through the CO pathway. This protective effect could be independent from the recovery of cardiac function.     

The influence of leptin on Th1/Th2 balance in obese children with asthma

OBJECTIVE:

In individuals with asthma, obesity induces the production of leptin and is associated with disease severity. Our objective was to evaluate the levels of serum leptin and their effect on Th1/Th2 balance in obese and non-obese children with asthma, as well as to investigate the association between serum leptin levels and clinical outcomes.

METHODS:

We evaluated 50 atopic children with physician-diagnosed moderate-to-severe persistent asthma and 20 controls. The children with asthma were divided into two groups, by body mass index percentile: obese (n = 25) and non-obese (n = 25). From all subjects, we collected peripheral blood samples in order to determine the levels of leptin, IFN-γ, and IL-4. Asthma severity was assessed by an asthma symptom score, and the results were correlated with the parameters studied.

RESULTS:

Serum leptin levels were significantly higher in the obese asthma group than in the non-obese asthma group, as well as being significantly higher in the children with asthma than in the controls, whereas IFN-γ levels were significantly higher and IL-4 levels were significantly lower in the obese asthma group than in the non-obese asthma group. In addition, the obese asthma group showed higher asthma symptom scores and significantly lower FEV₁ (% of predicted) than did the non-obese asthma group. There was a significant positive correlation between leptin and IFN-γ levels only in the obese asthma group.

CONCLUSIONS:

Although leptin is involved in the pathogenesis of asthma in obese and non-obese children, its effect is more pronounced in the former. In the presence of high leptin levels, only obese children with asthma exhibited Th1 polarization, with higher IFN-γ levels and greater asthma severity.