Viviane dos Santos Augusto

Oxidative-Stress Biomarkers in Patients with Pulmonary Hypertension

This controlled, prospective, nonrandomized clinical investigation has as its chief strength the fact that it was done in humans with active disease and apparently on fairly modest therapeutic regimens. The aim was to present the results of oxidative-stress biomarkers in humans suffering from pulmonary artery hypertension (PAH). Inflammation and oxidative stress are essential in PAH with increased lipid peroxidation and reduced antioxidant defenses. Twenty-four adult patients of both sexes, with a mean age of 21 years, were subdivided into 2 groups: a control group of 12 healthy, nonsmoking volunteers and a PAH group (PAHG) of 12 volunteers with PAH receiving outpatient treatment. Oxidative stress was evaluated by plasma activity of reduced glutathione (GSH); lipid peroxidation was expressed by malondialdehyde (MDA) and lipid hydroperoxide (ferrous oxidation of xylenol orange [FOX] assay); vitamin E was measured by high-performance liquid chromatography and tumor necrosis factor-α (TNF-α) by enzyme-linked immunosorbent assay. Statistical analyses showed significant differences for (1) the TNF-α measure, with highest values in PAHG patients; (2) the plasma GSH, with lowest values in PAHG patients; (3) vitamin E, with the lowest concentrations in PAHG patients; (4) MDA measure, with highest values in PAHG patients; and (5) the lipid hydroperoxide FOX measure, with highest values in PAHG patients. In conclusion, inflammation and oxidative stress are present in patients with PAH, as confirmed by increased lipid peroxidation, reduced GSH, and low concentrations of vitamin E.

Preoperative respiratory muscle dysfunction is a predictor of prolonged invasive mechanical ventilation in cardiorespiratory complications after heart valve surgery.

OBJECTIVE To verify whether preoperative respiratory muscle strength and ventilometric parameters, among other clinically relevant factors, are associated with the need for prolonged invasive mechanical ventilation (PIMV) due to cardiorespiratory complications following heart valve surgery. METHODS Demographics, preoperative ventilometric and manometric data, and the hospital course of 171 patients, who had undergone heart valve surgery at Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto, were prospectively collected and subjected to univariate analysis for identifying the risk factors for PIMV. RESULTS The hospital mortality was 7%. About 6% of the patients, who had undergone heart valve surgery required PIMV because of postoperative cardiorespiratory dysfunction. Their hospital mortality was 60% (vs 4%, p < 0.001). Univariate analysis revealed that preoperative respiratory muscle dysfunction, characterized by maximal inspiratory and expiratory pressure below 70% of the predicted values combined with respiratory rate above 15 rpm during ventilometry, was associated with postoperative PIMV (p = 0.030, odds ratio: 50, 95% confidence interval (CI): 1.2-18). Postoperative PIMV was also associated with: (1) body mass index (BMI)<18.5 (odds ratio: 7.2, 95% CI: 1.5-32), (2) body weight < 50 kg (odds ratio: 6.5, 95% CI: 1.6-25), (3) valve operation due to acute endocarditis (odds ratio: 5.5, 95% CI: 0.98-30), and (4) concomitant operation for mitral and tricuspid valve dysfunction (p = 0.047, odds ratio: 5.0, 95% CI: 1.1-22). CONCLUSION Our results have demonstrated that respiratory muscle dysfunction, among other clinical factors, is associated with the need for PIMV due to cardiovascular or pulmonary dysfunction after heart valve surgery.

Immunohistochemical evaluation of three nitric oxide synthase isoforms in human saphenous vein exposed to different degrees of distension pressures.

The effect of short duration and different degrees of distension pressures was investigated by means of immunohistochemistry of the three nitric oxide synthase isoforms in the human saphenous vein conventionally harvested from 20 patients submitted to coronary artery bypass graft. The human saphenous vein distal portion was divided into four segments, each one allocated to a different group. In Group I (control group), the human saphenous vein segment was not exposed to distension pressure. In Groups II, III, and IV, the human saphenous vein segment was exposed to 100, 200, and 300 mmHg of distension pressure, respectively. The distension pressures were applied and maintained with Krebs solution for 15 s. The human saphenous vein of the control group presented endothelial nitric oxide synthase and neuronal nitric oxide synthase in both endothelial and smooth muscle cells, while the inducible nitric oxide synthase appeared predominantly in the medial layer. Neither 100 nor 200 mmHg of pressurization affected the immunostaining of any nitric oxide synthase isoform. However, the human saphenous vein segments exposed to 300 mmHg of distension pressure showed a reduction in endothelial nitric oxide synthase content in the endothelium, but not in the tunica media. This lower endothelial nitric oxide synthase immunostaining in the intimal cells was associated with endothelial denudation. Therefore, we conclude that care should be taken when handling the human saphenous vein since just a few seconds of distension pressure above the normal systemic pressure can be sufficient to disrupt the endothelium reducing the amount of endothelial nitric oxide synthase and impairing the graft quality.

Carcinoid heart valve disease: still a puzzle and a challenge

Mailing Adress: Paulo Roberto Barbosa Evora • Rua Rui Barbosa 367/15 – Centro 14015-120 – Ribeirão Preto, SP Brasil E-mail: prbevora@cardiol.br, prbevora@fmrp.usp.br Manuscript received March 21, 2011; revised manuscript received March 21, 2011; accepted April 26, 2011. Carcinoid tumor is a rare tumor in neuroendocrine cell line, which occurs in 1.2 to 2.1 per 100,000 people per year. At diagnosis, 20% to 30% of patients have the disease disseminated and subsequent heart disease, which affects 40% of patients causing high morbidity and mortality in the carcinoid syndrome. Primary cardiac carcinoid tumors were not reported and, rarely, metastatic tumor masses were found in the myocardium, usually in conjunction with valvular involvement. It is believed that cardiac involvement occurs when serotonin and other active substances are released from liver metastases or primary ovarian carcinoid tumors, bypassing the metabolism in the liver. Carcinoid heart disease typically involves the tricuspid and pulmonary valves, causing right heart failure. Involvement of the left valve is rarely reported (<10% of patients). Thus, the mitral and aortic carcinoid disease may occur more frequently in patients with atrial septal defect or patent foramen ovale with diversion of blood from right to left. However, cardiac involvement may also occur in the absence of this diversion due to an association with bronchopulmonary carcinoid or with high levels of circulating serotonin1-3.

Exhaled breath condensate collection for nitrite dosage: a safe and low cost adaptation

PURPOSE Standardization of a simple and low cost technique of exhaled breath condensate (EBC) collection to measure nitrite. METHODS Two devices were mounted in polystyrene boxes filled either with crushed ice/salt crystals or dry ice/crushed ice. Blood samples were stored at -70 degrees C for posterior nitrite dosages by chemiluminescence and the Griess reaction. RESULTS a) The use of crushed ice/dry ice or salt revealed sufficient EBC room air collection, but was not efficient for patients under ventilation support; b) the method using crushed ice/salt collected greater EBC volumes, but the nitrite concentrations were not proportional to the volume collected; c) The EBC nitrite values were higher in the surgical group using both methods; d) In the surgical group the nasal clip use diminished the EBC nitrite concentrations in both methods. CONCLUSIONS The exhaled breath condensate (EBC) methodology collection was efficient on room air breathing. Either cooling methods provided successful EBC collections showing that it is possible to diminish costs, and, amongst the two used methods, the one using crushed ice/salt crystals revealed better efficiency compared to the dry ice method.

Evaluation of the Respiratory Muscle Strength of Cirrhotic Patients: Relationship With Child-Turcotte-Pugh Scoring System

Pulmonary abnormalities are observed in chronic hepatopathy. The measurement of the maximum inspiratory and expiratory pressure may evaluate lung function and the risks associated with hepatic transplantation. Thus, the present work sought to evaluate the respiratory muscle strength of 29 patients between 17 and 63 years old who were enrolled for liver transplantation. The patients were classified according to Child-Turcotte-Pugh score as A, B, or C, and also according to a physiotherapeutic evaluation, which included measurement of respiratory muscle strength by means of a digital manovacuometer, which determines the maximum inspiratory pressure (MaxIP) and the maximum expiratory pressure (MaxEP). The tests were performed with seated individuals having their nostrils obstructed by a nasal clip. The MaxIP was measured during the effort initiated in the residual volume, whereas the MaxEP was measured during the effort initiated in the total pulmonary capacity, keeping pressures stable for at least 1 second. The statistical analysis was performed through using the Mann-Whitney test with a 5% level of significance. The MaxIP values of Child A 95.5 +/- 40.507 cm H(2)O (average +/- DP) and Child B 87.2 +/- 35.02 patients were higher than those for Child C patients (34.83 +/- 3.68; P < .05). Similar results were observed for the MaxEP of Child A and B groups (116.25 +/- 31.98 and 97.28 +/- 31.08, respectively; P < .05), versus the Child C group (48.16 +/- 22.60). Between groups A and B, the MaxEP were similar (P > .05). We concluded that Child C patients display muscle weakness significantly greater than that of subjects classified as Child A or B.

Evaluation of Oxidative Stress in the Late Postoperative Stage of Liver Transplantation

INTRODUCTION Liver transplant recipients are at an increased oxidative stress risk due to pre-existing hepatic impairment, ischemia-reperfusion injury, immunosuppression, and functional graft rejection. This study compared the oxidative status of healthy control subjects, patients with liver cirrhosis on the list for transplantation, and subjects already transplanted for at least 12 months. PATIENTS AND METHODS Sixty adult male patients, aged between 27 and 67 years, were subdivided into 3 groups: a control group (15 healthy volunteers), a cirrhosis group (15 volunteers), and a transplant group (30 volunteers). Oxidative stress was evaluated by activity of reduced glutathione, malondialdehyde, and vitamin E. RESULTS There was a significant difference (P < .01) in the plasma concentration of reduced glutathione in the 3 groups, with the lowest values observed in the transplanted group. The malondialdehyde values differed significantly (P < .01) among the 3 groups, with the transplanted group again having the lowest concentrations. The lowest concentrations of vitamin E were observed in patients with cirrhosis compared with control subjects, and there was a significant correlation (P < .05) among the 3 groups. No correlations were found between reduced glutathione and vitamin E or between vitamin E and malondialdehyde. However, there were strong correlations between plasma malondialdehyde and reduced glutathione in the 3 groups: control group, r = 0.9972 and P < .0001; cirrhotic group, r = 0.9765 and P < .0001; and transplanted group, r = 0.8981 and P < .0001. CONCLUSIONS In the late postoperative stage of liver transplantation, oxidative stress persists but in attenuated form.

EXHALED AND PLASMA NITRITE: a comparative study among healthy, cirrhotic and liver transplant patients

CONTEXT There is a relative lack of studies about exhaled nitrite (NO2-) concentrations in cirrhotic and transplanted patients. OBJECTIVE Verify possible differences and correlations between the levels of NO2-, measured in plasma and exhaled breath condensate collected from patients with cirrhosis and liver transplant. METHOD Sixty adult male patients, aged between 27 and 67 years, were subdivided into three groups: a control group comprised of 15 healthy volunteers, a cirrhosis group composed of 15 volunteers, and a transplant group comprised of 30 volunteers. The NO2- concentrations were measured by chemiluminescence. RESULTS 1) The analysis of plasma NO2- held among the three groups showed no statistical significance. 2) The comparison between cirrhotic and control groups, control and transplanted and cirrhotic and transplanted was not statistically significant. 3) The measurements performed on of NO2- exhaled breath condensate among the three groups showed no statistical difference. 4) When comparing the control group samples and cirrhotic, control and transplanted and cirrhotic and transplanted, there was no significant changes in the concentrations of NO2-. CONCLUSION No correlations were found between plasma and exhaled NO2-, suggesting that the exhaled NO2- is more reflective of local respiratory NO release than the systemic circulation.

Glycol methacrylate-embedding medium to study morphological alterations of saphenous vein under brief and crescent pressurizations

PURPOSE This study sought to evaluate the efficiency of glycol methacrylate-embedding medium to detect morphological alterations of human saphenous vein submitted to brief and crescent pressurizations. METHODS Saphenous veins of 20 CABG patients were randomly distributed into four experimental groups (control, 100, 200 and 300 mmHg pressures during 15 seconds). To quantify the percentage of endothelium spread over vein surface a microscope magnification of 100x was used for measurements. Morphometric analysis was performed using videomicroscopy with the Leica Qwin software in conjunction with a Leica microscope, videocamera, and an on-line computer. RESULTS A slight tendency of quantitative increase was observed in all parameters including percentage of endothelium spread over vein surface and thickness of saphenous vein walls (intima and media layers). CONCLUSIONS The glycol methacrylate-embedding allowed sections with adequate resolution of structural details and revealed to be an extremely useful method to study pressurized human saphenous veins.

Predicted preoperative maximal static respiratory pressures in adult cardiac surgeries: evaluation of two formulas

OBJECTIVES Cardiac surgery (CC) determines systemic and pulmonary changes that require special care. Awareness of the importance of respiratory muscle dysfunction in the development of respiratory failure motivated several studies conducted in healthy subjects to assess muscle strength. These studies were carried out by evaluating the maximal inspiratory pressure (MIP) and maximal expiratory pressure (MEP) values. This study examined the concordance among the values predicted by the equations proposed by Black & Hyatt and Neder, and the measured values in cardiac surgery (CS) patients. METHODS Data were collected from preoperative evaluation forms. The Lin coefficient and Bland-Altman plots were used for statistical concordance analysis. The multiple linear regression and analysis of variance (ANOVA) were used to produce new formulas. RESULTS There were weak correlations of 0.22 and 0.19 in the MIP analysis and of 0.10 and 0.32 in the MEP analysis, for the formulas of Black & Hyatt and Neder, respectively. The ANOVA for both MIP and MEP were significant (P <0.0001), and the following formulas were developed: MIP = 88.82 - (0.51 x age) + (19.86 x gender), and MEP = 91.36 - (0.30 x age) + (29.92 x gender). CONCLUSIONS The Black and Hyatt and Neder formulas predict highly discrepant values of MIP and MEP and should not be used to identify muscle weakness in CS patients.