Carlos Fernando Ronchi

Effects of Inhaled Nitric Oxide on Oxidative Stress and Histopathological and Inflammatory Lung Injury in a Saline-Lavaged Rabbit Model of Acute Lung Injury

BACKGROUND: Conventional mechanical ventilation (CMV) is fundamental in acute respiratory distress syndrome (ARDS) treatment. Inhaled nitric oxide (INO), an adjunctive therapy, has been used with ventilation in an attempt to improve oxygenation and reduce lung injury. OBJECTIVE: To analyze the early effects of low INO dose on oxygenation, oxidative stress, inflammatory, and histopathological lung injury in a rabbit model of acute lung injury (ALI). METHODS: This was a prospective, controlled, in vivo animal laboratory study. Forty rabbits were instrumented and ventilated at FIO2 1.0. ALI was induced by tracheal infusion of warm saline (30 mL/kg, 38°C) and lung oxidative stress was assessed by total antioxidant performance (TAP) assay. Animals were assigned to groups: control group (no. = 10, low tidal volume [VT] = 6 mL/kg, PEEP = 5 cm H2O), ALI without INO (no-INO group, no. = 10, low VT = 6 mL/kg, PEEP = 10 cm H2O), ALI plus INO (INO group, no. = 10, low VT = 6 mL/kg, PEEP = 10 cm H2O, INO = 5 ppm). Plateau pressure was limited to 30 cm H2O in all groups. Ten non-instrumented animals (healthy group) were studied for TAP assay. Ventilatory and hemodynamic parameters were recorded every 30 min for 4 hours. RESULTS: After lung injury, the instrumented groups were worse than the control group for PaO2 (control group 438 ± 87 mm Hg, no-INO group 80 ± 13 mm Hg, INO group 81 ± 24 mm Hg, P < .001). The INO group showed decreased lung inflammation by leukocyte count in lung lavage fluid (no-INO group 4.8 ± 1.64, control group 0.16 ± 0.15, INO group 0.96 ± 0.35 polymorphonuclear cells × 106/bronchoalveolar lavage fluid/lung, P < .001), decreased histopathological injury score (no-INO group 5 [range 1–16], INO group 2 [range 0–5], control group 0 [range 0–3], P < .001), and better lung protection against oxidative injury than the no-INO group (healthy group 68 ± 8.7, control group 66.4 ± 6.8, INO group 56.3 ± 5.1, no-INO group 45.9 ± 3.4 percent protection/g protein, P < .001). CONCLUSIONS: INO attenuates oxidative stress and histopathological and inflammatory lung injury in a saline-lavaged rabbit ALI model.

High-frequency oscillatory ventilation attenuates oxidative lung injury in a rabbit model of acute lung injury

Mechanical ventilation (MV) can induce lung oxidative stress, which plays an important role in pulmonary injury. This study compared protective conventional mechanical ventilation (CMV) and high-frequency oscillatory ventilation (HFOV) for oxygenation, oxidative stress, inflammatory and histopathological lung injury in a rabbit model of acute lung injury (ALI). Rabbits (n = 30) were ventilated at FiO2 1.0. Lung injury was induced by tracheal saline infusion (30 mL/kg, 38°C). Animals were randomly assigned to: (a) sham control (CG: tidal volume [V T] 6 mL/kg, positive end expiratory pressure [PEEP] 5 cmH2O, respiratory rate [RR] 40 ipm); (b) ALI + CMV (CMVG: V T 6 mL/kg, PEEP 10 cmH2O, RR 40 ipm); or (c) ALI + HFOV (HFG: mean airway pressure [Paw] 14 cmH2O, RR 10 Hz) groups. Lung oxidative stress was assessed by total antioxidant performance assay, inflammatory response by the number of polymorphonuclear leukocytes/bronchoalveolar lavage fluid/lung and pulmonary histological damage was quantified by a score. Ventilatory and hemodynamic parameters were recorded every 30 min. Both ALI groups showed worse oxygenation after lung injury induction. After four hours of ventilation, HFG showed better oxygenation (partial pressure of oxygen [PaO2] – CG: 465.9 ± 30.5 = HFG: 399.1 ± 98.2 > CMVG: 232.7 ± 104 mmHg, P < 0.05) and inflammatory responses (CMVG: 4.27 ± 1.50 > HFG: 0.33 ± 0.20 = CG: 0.16 ± 0.15; polymorphonuclear cells/bronchoalveolar lavage fluid/lung, P < 0.05), less histopathological injury score (CMVG: 5 [1–16] > HFG: 1 [0–5] > CG: 0 [0–3]; P < 0.05), and lower lung oxidative stress than CMVG (CG: 59.4 ± 4.52 = HFG: 69.0 ± 4.99 > CMVG: 47.6 ± 2.58% protection/g protein, P < 0.05). This study showed that HFOV had an important protective role in ALI. It improved oxygenation, reduced inflammatory process and histopathological damage, and attenuated oxidative lung injury compared with protective CMV under these experimental conditions considering the study limitations.

Respiratory muscular strength decrease in children with mylomeningocele

Study Design. Case-control study. Objective. To evaluate respiratory muscle force in children with myelomeningocele. Summary of Background Data. Myelomeningocele is a common spinal cord malformation with limitations linked to central nervous system lesions and abnormalities in respiratory movements. Despite this, little attention has been given to evaluating respiratory muscle force in these patients. Methods. Children with myelomeningocele aged between 4 and 14 years (myelomeningocele group; MG, n = 20) were studied and compared with healthy children (control group; CG, n = 20) matched for age and gender. Respiratory muscular force was evaluated by maximum inspiratory (Pimax) and expiratory (Pemax) pressures. Results. Groups were similar for age [CG = 8 (6–13) × MG = 8 (4–14), P > 0.05]; gender, and body mass index [CG = 17.4 (14.1–24.7) × MG = 19.2 (12.6–31.9), P > 0.05]. The lumbosacral region was predominantly affected (45%). Maximum respiratory pressures were significantly higher in CG than MG (Pimax = CG: −83 ± 21.75 > MG: −54.1 ± 23.66; P < 0.001 and Pemax = CG: +87.4 ± 26.28 > MG: +64.6 ± 26.97; P = 0.01). Patients with upper spinal lesion (UL) had lower maximum respiratory pressure values than those with lower spinal lesion (LL), [Pimax (UL = −38.33 ± 11.20 cm H2O × LL = −60.85 ± 24.62 cm H2O), P < 0.041 and Pemax (UL = +48 ± 20.82 cm H2O × LL + 71.71 ± 26.73 cm H2O), P = 0.067]). Conclusion. Children with myelomeningocele at the ages studied presented reduced respiratory muscle force with more compromise in upper spinal lesion.

Association of pre and intraoperative variables with postoperative complications in coronary artery bypass graft surgery

Objective To associate the pre- and intraoperative variables with postoperative complications of patients undergoing coronary artery bypass graft surgery. Methods The pre- and intraoperative risk factors of individuals of both genders with diagnosis of coronary insufficiency undergoing coronary artery bypass graft have been studied. Results Fifty-eight individuals with median age 62 ± 10 year-old were included in the study, 67% of whom were male. Fourteen (24.1%) patients were smokers, 39 (67.2%) had previous myocardial infarction history, 11 (19%) had undergone coronary angioplasty, 74% had hypertension, 27% had diabetes mellitus, 64% had dyslipidemia and 15.5% had chronic obstructive pulmonary disease. Eighteen (31%) patients presented postoperative complications, most frequent being: infection in surgical incision, difficulties in deambulation, dyspnea, urinary infection and generalized weakness. Male patients had fewer complications than females (P=0.005). Patients with chronic obstructive pulmonary disease remained hospitalized for longer time periods (P=0.019). Postoperative complications occurred in 50% of the patients with creatinine increased, while only 27.1% of the patients with normal value of creatinine had complications (P=0.049). In addition, complications occurred in 50% of the patients with diabetes mellitus, while only 23.8% of patients without diabetes mellitus had complications (P=0.032). The intraoperative factors showed no statistically significant differences. Conclusion The preoperative factors are associated with postoperative complications in patients undergoing coronary artery bypass graft surgery.

Interactive effects of mechanical ventilation, inhaled nitric oxide and oxidative stress in acute lung injury

To compare conventional mechanical ventilation (CMV) and high-frequency oscillatory ventilation (HFOV), with/without inhaled nitric oxide (iNO), for oxygenation, inflammation, antioxidant/oxidative stress status, and DNA damage in a model of acute lung injury (ALI). Lung injury was induced by tracheal infusion of warm saline. Rabbits were ventilated at [Formula: see text] 1.0 and randomly assigned to one of five groups. Overall antioxidant defense/oxidative stress was assessed by total antioxidant performance assay, and DNA damage by comet assay. Ventilatory and hemodynamic parameters were recorded every 30min for 4h. ALI groups showed worse oxygenation than controls after lung injury. After 4h of mechanical ventilation, HFOV groups presented significant improvements in oxygenation. HFOV with and without iNO, and CMV with iNO showed significantly increased antioxidant defense and reduced DNA damage than CMV without iNO. Inhaled nitric oxide did not beneficially affect HFOV in relation to antioxidant defense/oxidative stress and pulmonary DNA damage. Overall, lung injury was reduced using HFOV or CMV with iNO.

Ventilator-Induced Lung Injury and Acute Respiratory Distress Syndrome: A Basic Science Review

Acute respiratory distress syndrome is the most severe manifestation of acute lung injury and it is associated with high mortality rate. Despite better understanding of ARDS pathophysiology, its mechanism is still unclear. Mechanical ventilation is the main ARDS supportive treatment. However, mechanical ventilation is a non-physiologic process and complications are associated with its application. Mechanical ventilation may induce lung injury, referred to as ventilator-induced lung injury. Frequently, VILI is related to macroscopic injuries associated with alveolar rupture. The present article is a review of the literature on ventilator-induced lung injury in acute respiratory distress syndrome. Animal and human studies were reviewed. We mainly selected publications in the past 5 years, but did not exclude commonly referenced and highly regarded older publications.

Biomarkers for oxidative stress in acute lung injury induced in rabbits submitted to different strategies of mechanical ventilation

Oxidative damage has been said to play an important role in pulmonary injury, which is associated with the development and progression of acute respiratory distress syndrome (ARDS). We aimed to identify biomarkers to determine the oxidative stress in an animal model of acute lung injury (ALI) using two different strategies of mechanical ventilation. Rabbits were ventilated using either conventional mechanical ventilation (CMV) or high-frequency oscillatory ventilation (HFOV). Lung injury was induced by tracheal saline infusion (30 ml/kg, 38°C). In addition, five healthy rabbits were studied for oxidative stress. Isolated lymphocytes from peripheral blood and lung tissue samples were analyzed by alkaline single cell gel electrophoresis (comet assay) to determine DNA damage. Total antioxidant performance (TAP) assay was applied to measure overall antioxidant performance in plasma and lung tissue. HFOV rabbits had similar results to healthy animals, showing significantly higher antioxidant performance and lower DNA damage compared with CMV in lung tissue and plasma. Total antioxidant performance showed a significant positive correlation (r = 0.58; P = 0.0006) in plasma and lung tissue. In addition, comet assay presented a significant positive correlation (r = 0.66; P = 0.007) between cells recovered from target tissue and peripheral blood. Moreover, antioxidant performance was significantly and negatively correlated with DNA damage (r = -0.50; P = 0.002) in lung tissue. This study indicates that both TAP and comet assay identify increased oxidative stress in CMV rabbits compared with HFOV. Antioxidant performance analyzed by TAP and oxidative DNA damage by comet assay, both in plasma, reflects oxidative stress in the target tissue, which warrants further studies in humans.

Bioavailability of plant pigment phytochemicals in Angelica keiskei in older adults: A pilot absorption kinetic study.

BACKGROUND/OBJECTIVES Angelica keiskei is a green leafy vegetable rich in plant pigment phytochemicals such as flavonoids and carotenoids. This study examined bioavailability of flavonoids and carotenoids in Angelica keiskei and the alteration of the antioxidant performance in vivo. SUBJECTS AND MATERIALS Absorption kinetics of phytochemicals in Angelica keiskei were determined in healthy older adults (> 60 y, n = 5) and subjects with metabolic syndrome (n = 5). Subjects consumed 5 g dry Angelica keiskei powder encapsulated in gelatin capsules with a low flavonoid and carotenoid liquid meal. Plasma samples were collected at baseline, 0.5, 1, 2, 3, 4, 5, 6, 7, and 8 h. Samples were analyzed for flavonoids and carotenoids using HPLC systems with electrochemical and UV detection, respectively, and for total antioxidant performance by fluorometry. RESULTS After ingestion of Angelica keiskei increases in plasma quercetin concentrations were observed at 1-3 and 6-8 hr in the healthy group and at all time points in the metabolic syndrome group compared to baseline (P < 0.05). Plasma lutein concentrations were significantly elevated in both the healthy and metabolic syndrome groups at 8 hr (P < 0.05). Significant increases in total antioxidant performance were also observed in both the healthy and the metabolic syndrome groups compared to baseline (P < 0.05). CONCLUSIONS Findings of this study clearly demonstrate the bioavailability of phytonutrients of Angelica keiskei and their ability to increase antioxidant status in humans.

Aplicabilidade das equações de referência para o teste de caminhada de seis minutos em adultos e idosos saudáveis de um município do estado de São Paulo

RESUMO | O teste de caminhada de seis minutos (TC6) tem sido considerado simples, seguro, de fácil administração, além de fornecer resultados representativos sobre atividades habituais do dia a dia. Os objetivos do estudo foram avaliar e comparar a distância percorrida no TC6 com as distâncias previstas por equações disponíveis na literatura científica em adultos e idosos saudáveis do município de São Carlos (SP), e verificar a aplicabilidade dessas equações nessa população. Foram avaliados 43 indivíduos (23 homens), dos 55 aos 78 anos, por meio da avaliação física, espirometria e do TC6. Observamos que a distância percorrida no TC6 foi significativamente (teste t-pareado: p<0,05) maior que os valores previstos pelas equações de Enright e Sherril, Masmoudi et al., Alameri, Al-Majed e Al-Howaikan e Dourado, Vidotto e Guerra, e os mesmos foram significativamente menores que os previstos por Troosters, Gosselink e Decramer, Gibbons, Enright, Camarri, Ben Saad e Soares e Pereira. Não foram observadas diferenças significativas entre a distância percorrida no TC6 e os valores previstos pelas equações de Chetta et al. e Iwama et al. A maioria das equações de referências utilizadas no presente estudo subestima ou superestima os valores obtidos no TC6, exceto as propostas por Chetta ABSTRACT | The six-minute walk test (6MWT) has been considered simple, safe, easy administration, and provide representative results about normal activities of day-to-day. The objective of the study was to evaluate and compare the 6-min walk distance (6MWD) with predicted distance by reference equations available in the scientific literature in healthy elderly adults, and to verify the applicability of these reference equations in this population. Forty-three elderly adults apparently healthy (23 males) between 55 to 78 years old were assessed by means of general physical assessment, the spirometry and 6MWT. The 6MWT was performed twice, with 30-min interval between them. The 6MWD was significantly (paired t-test: p<0.05) higher than those predicted by the equations of Enright and Sherrill, Masmoudi et al., Alameri, Al-Majed and Al-Howaikan and Dourado, Vidotto and Guerra, and they were significantly lower than those provided by Troosters, Gosselink and Decramer, Gibbons et al., Enright et al., Camarri et al., Ben Saad et al. and Soares and Pereira. No significant differences were observed between the 6MWD and the predicted values by the equations of Chetta et al. and Iwama et al. Most reference equations used underestimates or overestimates the 6MWD, except of the Chetta et al., and Iwama et al. that showed acceptable to this population. There difference between the distances, even when the 6MWT is realized with similar methodology and rigorous standardization, thus emphasizes the need for specific equations for each population. Applicability of reference equations for the six-minute walk test in healthy elderly adults in a municipality of São Paulo Aplicabilidade das equações de referência para o teste de caminhada de seis minutos em adultos e idosos saudáveis de um município do estado de São Paulo Aplicabilidad de las ecuaciones de referencia para el test de marcha de seis minutos en adultos y adultos mayores saludables de un municipio del estado de Sao Paulo

Aplicabilidad de las ecuaciones de referencia para el test de marcha de seis minutos en adultos y adultos mayores saludables de un municipio del estado de Sao Paulo

RESUMO | O teste de caminhada de seis minutos (TC6) tem sido considerado simples, seguro, de fácil administração, além de fornecer resultados representativos sobre atividades habituais do dia a dia. Os objetivos do estudo foram avaliar e comparar a distância percorrida no TC6 com as distâncias previstas por equações disponíveis na literatura científica em adultos e idosos saudáveis do município de São Carlos (SP), e verificar a aplicabilidade dessas equações nessa população. Foram avaliados 43 indivíduos (23 homens), dos 55 aos 78 anos, por meio da avaliação física, espirometria e do TC6. Observamos que a distância percorrida no TC6 foi significativamente (teste t-pareado: p<0,05) maior que os valores previstos pelas equações de Enright e Sherril, Masmoudi et al., Alameri, Al-Majed e Al-Howaikan e Dourado, Vidotto e Guerra, e os mesmos foram significativamente menores que os previstos por Troosters, Gosselink e Decramer, Gibbons, Enright, Camarri, Ben Saad e Soares e Pereira. Não foram observadas diferenças significativas entre a distância percorrida no TC6 e os valores previstos pelas equações de Chetta et al. e Iwama et al. A maioria das equações de referências utilizadas no presente estudo subestima ou superestima os valores obtidos no TC6, exceto as propostas por Chetta ABSTRACT | The six-minute walk test (6MWT) has been considered simple, safe, easy administration, and provide representative results about normal activities of day-to-day. The objective of the study was to evaluate and compare the 6-min walk distance (6MWD) with predicted distance by reference equations available in the scientific literature in healthy elderly adults, and to verify the applicability of these reference equations in this population. Forty-three elderly adults apparently healthy (23 males) between 55 to 78 years old were assessed by means of general physical assessment, the spirometry and 6MWT. The 6MWT was performed twice, with 30-min interval between them. The 6MWD was significantly (paired t-test: p<0.05) higher than those predicted by the equations of Enright and Sherrill, Masmoudi et al., Alameri, Al-Majed and Al-Howaikan and Dourado, Vidotto and Guerra, and they were significantly lower than those provided by Troosters, Gosselink and Decramer, Gibbons et al., Enright et al., Camarri et al., Ben Saad et al. and Soares and Pereira. No significant differences were observed between the 6MWD and the predicted values by the equations of Chetta et al. and Iwama et al. Most reference equations used underestimates or overestimates the 6MWD, except of the Chetta et al., and Iwama et al. that showed acceptable to this population. There difference between the distances, even when the 6MWT is realized with similar methodology and rigorous standardization, thus emphasizes the need for specific equations for each population. Applicability of reference equations for the six-minute walk test in healthy elderly adults in a municipality of São Paulo Aplicabilidade das equações de referência para o teste de caminhada de seis minutos em adultos e idosos saudáveis de um município do estado de São Paulo Aplicabilidad de las ecuaciones de referencia para el test de marcha de seis minutos en adultos y adultos mayores saludables de un municipio del estado de Sao Paulo