Pera orange juice (Citrus sinensis L. Osbeck) alters lipid metabolism and attenuates oxidative stress in the heart and liver of rats treated with doxorubicin.

Background: Doxorubicin (DOX) is a highly effective chemotherapy drug widely used to treat cancer, but its use is limited due to multisystemic toxicity. Lipid metabolism is also affected by doxorubicin. Orange juice can reduce dyslipidemia in other clinical situations and has already been shown to attenuate cardiotoxicity. Our aim is to evaluate the effects of Pera orange juice (Citrus sinensis L. Osbeck) on mitigating lipid metabolism imbalance, metabolic pathways, and DOX induced cytotoxic effects in the heart and liver. Methods: Twenty-four male Wistar rats were allocated into 3 groups: Control (C); DOX (D); and DOX plus Pera orange juice (DOJ). DOJ received orange juice for 4 weeks, while C and D received water. At the end of each week, D and DOJ groups received 4 mg/kg/week DOX, intraperitoneal. At the end of 4 weeks animals were submitted to echocardiography and euthanasia. Results: Animals treated with DOX decreased water intake and lost weight over time. At echocardiography, DOX treated rats presented morphologic alterations in the heart. DOX increased aspartate aminotransferase (AST), alanine aminotransferase (ALT), total cholesterol, high density lipoprotein (HDL), low-density lipoprotein (LDL), and triglycerides. It also reduced superoxide dismutase (SOD) activity, increased protein carbonylation in the heart and dihydroethidium (DHE) expression in the liver, decreased glucose transporter type 4 (GLUT4) and the nuclear receptor peroxisome proliferator-activated receptor γ (PPARγ1) in the heart, and reduced carnitine palmitoyltransferase I (CPT1) in the liver. Conclusion: DOX caused dyslipidemia, liver and cardiac toxicity by increasing oxidative stress, and altered energy metabolic parameters in both organs. Despite not improving changes in left ventricular morphology, orange juice did attenuate oxidative stress and mitigate the metabolic effects of DOX.

Protective Effects of Omega-3 Supplementation against Doxorubicin-Induced Deleterious Effects on the Liver and Kidneys of Rats.

Anthracycline doxorubicin (DOX) is still widely used as a chemotherapeutic drug for some solid tumors. Although DOX is highly effective, its side effects are limiting factors, such as cardio, nephro and hepatotoxicity. As such, approaches used to mitigate these adverse effects are highly encouraged. Omega 3 (ω-3), which is a class of long-chain polyunsaturated fatty acids, has been shown to have anti-inflammatory and antioxidant effects in preclinical bioassays. Thus, we evaluated the protective effects of ω-3 supplementation on hepatotoxicity and nephrotoxicity induced by multiple DOX administrations in rodents. Male Wistar rats (10 rats/group) were treated daily with ω-3 (400 mg/kg/day) by gavage for six weeks. Two weeks after the first ω-3 administration, the rats received DOX (3.5 mg/kg, intraperitoneal, 1×/week) for four weeks. DOX treatment reduced body weight gain increased systemic genotoxicity and caused liver-related (increase in serum ALT levels, thickness of the Glisson's capsule, compensatory proliferation and p65 levels) and kidney-related (increase in serum urea and creatinine levels, and incidence of tubular dilatation) deleterious outcomes. In contrast, ω-3 supplementation was safe and abrogated the DOX-related enhancement of systemic genotoxicity, serum urea and creatinine levels. Furthermore, ω-3 intervention reduced by 50% the incidence of kidney histological lesions while reducing by 40-50% the p65 protein level, and the proliferative response in the liver induced by DOX. Our findings indicate that ω-3 intervention attenuated the DOX-induced deleterious effects in the liver and kidney. Therefore, our findings may inspire future mechanistical investigations and clinical interventions with ω-3 on the reported outcomes.

Reduced mobility is associated with adverse outcomes after in-hospital cardiac arrest

SUMMARY OBJECTIVE: In-hospital cardiac arrest is a critical medical emergency. Knowledge of prognostic factors could assist in cardiopulmonary resuscitation decision-making. Frailty and functional status are emerging risk factors and may play a role in prognostication. The objective was to evaluate the association between reduced mobility and in-hospital cardiac arrest outcomes. METHODS: This retrospective cohort study included patients over 18 years of age with in-hospital cardiac arrest in Botucatu, Brazil, from April 2018 to December 2021. Exclusion criteria were patients with a do-not-resuscitate order or patients with recurrent in-hospital cardiac arrest. Reduced mobility was defined as the need for a bed bath 48 h before in-hospital cardiac arrest. The outcomes of no return of spontaneous circulation and in-hospital mortality were evaluated. RESULTS: A total of 387 patients were included in the analysis. The mean age was 65.4±14.8 years; 53.7% were males and 75.4% had reduced mobility. Among the evaluated outcomes, the no return of spontaneous circulation rate was 57.1%, and in-hospital mortality was 94.3%. In multivariate analysis, reduced mobility was associated with no return of spontaneous circulation when adjusted by age, gender, initial shockable rhythm, duration of cardiopulmonary resuscitation, and epinephrine administration. However, in multiple logistic regression, there was no association between reduced mobility and in-hospital mortality. CONCLUSION: In patients with in-hospital cardiac arrest, reduced mobility is associated with no return of spontaneous circulation. However, there is no relation to in-hospital mortality.

Açai supplementation (Euterpe oleracea Mart.) attenuates cardiac remodeling after myocardial infarction in rats through different mechanistic pathways.

Myocardial infarction has a high mortality rate worldwide. Therefore, clinical intervention in cardiac remodeling after myocardial infarction is essential. Açai pulp is a natural product and has been considered a functional food because of its antioxidant/anti-inflammatory properties. The aim of the present study was to analyze the effect of açai pulp supplementation on cardiac remodeling after myocardial infarction in rats. After 7 days of surgery, male Wistar rats were assigned to six groups: sham animals fed standard chow (SA0, n = 14), fed standard chow with 2% açai pulp (SA2, n = 12) and fed standard chow with 5% açai pulp (SA5, n = 14), infarcted animals fed standard chow (IA0, n = 12), fed standard chow with 2% açai pulp (IA2, n = 12), and fed standard chow with 5% açai pulp (IA5, n = 12). After 3 months of supplementation, echocardiography and euthanasia were performed. Açai pulp supplementation, after myocardial infarction, improved energy metabolism, attenuated oxidative stress (lower concentration of malondialdehyde, P = 0.023; dose-dependent effect), modulated the inflammatory process (lower concentration of interleukin-10, P<0.001; dose-dependent effect) and decreased the deposit of collagen (lower percentage of interstitial collagen fraction, P<0.001; dose-dependent effect). In conclusion, açai pulp supplementation attenuated cardiac remodeling after myocardial infarction in rats. Also, different doses of açai pulp supplementation have dose-dependent effects on cardiac remodeling.

A Review of Current Clinical Concepts in the Pathophysiology, Etiology, Diagnosis, and Management of Hypercalcemia.

Calcium is the most abundant extracellular cation in the body, and it is responsible for structural and enzymatic functions. Calcium homeostasis is regulated by 3 factors: calcitonin, vitamin D, and parathyroid hormone (PTH). Hypercalcemia is defined by a serum calcium concentration >10.5 mg/dL, and it is classified into mild, moderate, and severe, depending on calcium values. Most cases are caused by primary hyperparathyroidism and malignancies. Various mechanisms are involved in the pathophysiology of hypercalcemia, such as excessive PTH production, production of parathyroid hormone-related protein (PTHrp), bone metastasis, extrarenal activation of vitamin D, and ectopic PTH secretion. The initial approach is similar in most cases, but a definitive treatment depends on etiology, that is why etiological investigation is mandatory in all cases. The majority of patients are asymptomatic and diagnosed during routine exams; only a small percentage of patients present with severe manifestations which can affect neurological, muscular, gastrointestinal, renal, and cardiovascular systems. Clinical manifestations are related to calcium levels, with higher values leading to more pronounced symptoms. Critically ill patients should receive treatment as soon as diagnosis is made. Initial treatment involves vigorous intravenous hydration and drugs to reduce bone resorption such as bisphosphonates and, more recently, denosumab, in refractory cases; also, corticosteroids and calcitonin can be used in specific cases. This review aims to provide a clinical update on current concepts of the pathophysiology of calcium homeostasis, epidemiology, screening, clinical presentation, diagnosis, and management of hypercalcemia.

Pera orange (Citrus sinensis) and Moro orange (Citrus sinensis (L.) Osbeck) juices attenuate left ventricular dysfunction and oxidative stress and improve myocardial energy metabolism in acute doxorubicin-induced cardiotoxicity in rats.

OBJECTIVES: Doxorubicin is a highly effective chemotherapeutic agent for treating several types of cancer; however, it can induce cardiotoxicity. We evaluated the influence of Pera and Moro orange juices on cardiac remodeling induced by acute administration of doxorubicin in rats. METHODS: We allocated 120 male Wistar rats into six groups: control (C), Pera orange juice (PO), Moro orange juice (MO), doxorubicin (D), doxorubicin + Pera orange juice (DPO), and doxorubicin + Moro orange juice (DMO). Groups PO and DPO received Pera orange juice, MO and DMO received Moro orange juice, and C and D received water with maltodextrin (100 g/L) for 4 wk. Subsequently, groups D, DPO, and DMO received 20 mg/kg doxorubicin and C, PO, and MO received saline. Echocardiogram and euthanasia were performed 48 h after doxorubicin injection. Juice and animal-serum flavonoid identification and quantification were evaluated by liquid chromatography/electrospray ionization multistage mass spectrometry. Oxidative stress and myocardial metabolism were evaluated by spectrophotometry. RESULTS: Systolic and diastolic left ventricular dysfunction increased oxidative stress and pathologic changes in myocardial energy metabolism of rats treated with doxorubicin. Intake of both orange juices improved left ventricular function, decreased oxidative stress, and attenuated the myocardial energy metabolism changes. Moro orange juice had a more pronounced effect than Pera orange juice in glutathione peroxidase activity, citrate synthase, and ß-hydroxyacyl-CoA dehydrogenase activity. CONCLUSIONS: Pera and Moro orange juices attenuated cardiac remodeling induced by doxorubicin, improved myocardial energy metabolism, and attenuated oxidative stress. However, Moro orange juice was more effective than Pera orange juice in modifying energy metabolism.

Clinical trials in cardiac xenotransplantation: Are we ready to overcome barriers?

Heart allotransplantation has become one of the methods of choice in the treatment of severe heart failure. In the face of its difficulties, such as the unmet balance between organ supply and demand, the use of xenotransplantation (XTx) might be an attractive option shortly, even more with the ongoing progress achieved regarding the avoidance of hyperacute rejection and primary organ disfunction, maintenance of xenograft function and control of xenograft growth. To make possible this translational challenge, some points must be taken into account indeed, and they are the equipoise of human benefit and animal suffering, the risk of unknown infections, a well prepared informed consent, ethical and religious beliefs, and the role of cardiac XTx in a ventricular assistance device era.

Evaluation of peptidylarginine deiminase 4 and PADI4 polymorphisms in sepsis-induced acute kidney injury

SUMMARY BACKGROUND: The aim of this study is to evaluate the peptidylarginine deiminase 4 (PAD 4) concentration and PADI4 polymorphisms as predictors of acute kidney injury (AKI) development, the need for renal replacement therapy (RRT), and mortality in patients with septic shock. METHODS: We included all individuals aged ≥ 18 years, with a diagnosis of septic shock at ICU admission. Blood samples were taken within the first 24 hours of the patient's admission to determine serum PAD4 concentration and its PADI4 polymorphism (rs11203367) and (rs874881). Patients were monitored during their ICU stay and the development of SAKI was evaluated. Among the patients in whom SAKI developed, mortality and the need for RRT were also evaluated. RESULTS: There were 99 patients, 51.5% of whom developed SAKI and of these, 21.5% needed RRT and 80% died in the ICU. There was no difference between PAD4 concentration (p = 0.116) and its polymorphisms rs11203367 (p = 0.910) and rs874881 (p = 0.769) in patients in whom SAKI did or did not develop. However, PAD4 had a positive correlation with plasma urea concentration (r = 0.269 and p = 0.007) and creatinine (r = 0.284 and p = 0.004). The PAD4 concentration and PADI4 polymorphisms were also not associated with RRT and with mortality in patients with SAKI. CONCLUSION: PAD4 concentration and its polymorphisms were not associated with SAKI development, the need for RRT, or mortality in patients with septic shock. However, PAD4 concentrations were associated with creatinine and urea levels in these patients.

RESUMO OBJETIVO: Avaliar a concentração da peptidilarginina deiminase 4 (PAD4) e os polimorfismos de PADI4, como preditores de desenvolvimento de lesão renal aguda, necessidade de terapia renal substitutiva (TRS) e mortalidade em pacientes com choque séptico. MÉTODOS: Foram incluídos indivíduos com idade ≥18 anos, com diagnóstico de choque séptico na admissão na Unidade de Terapia Intensiva (UTI). Amostras de sangue foram coletadas nas primeiras 24 horas após a admissão do paciente para determinar a concentração sérica de PAD4 e seus polimorfismos PADI4 (rs11203367) e (rs874881). Os pacientes foram acompanhados durante a internação na UTI e tiveram avaliados desenvolvimento da lesão renal aguda séptica (Sepsis-induced acute kidney injury - Saki), necessidade TRS e mortalidade. RESULTADOS: Foram avaliados 99 pacientes; 51,5% desenvolveram Saki e, desses, 21,5% necessitaram de TRS e 80% morreram na UTI. Não houve diferença entre a concentração de PAD4 (p=0,116) e seus polimorfismos rs11203367 (p=0,910) e rs874881 (p=0,769) entre os pacientes. No entanto, o PAD4 apresentou correlação positiva com a concentração plasmática de ureia (r=0,269; p=0,007) e creatinina (r=0,284; p=0,004). A concentração de PAD4 e os polimorfismos da PADI4 também não foram associados à TRS e à mortalidade em pacientes com Saki. CONCLUSÕES: A concentração de PAD4 e seus polimorfismos não foram associados ao desenvolvimento de Saki, à necessidade de TRS ou à mortalidade em pacientes com choque séptico. No entanto, as concentrações de PAD4 foram associadas às concentrações de creatinina e ureia nesses pacientes.

Spondias mombin L. attenuates ventricular remodelling after myocardial infarction associated with oxidative stress and inflammatory modulation.

The objective of this study was to evaluate Spondias mombin L. (SM) pulp and its influence on cardiac remodelling after myocardial infarction (MI). Male Wistar rats were assigned to four groups: a sham group (animals underwent simulated surgery) that received standard chow (S; n = 20), an infarcted group that received standard chow (MI; n = 24), an infarcted group supplemented with 100 mg of SM/kg bodyweight/d, (MIS100; n = 23) and an infarcted group supplemented with 250 mg of SM/kg bodyweight/d (MIS250; n = 22). After 3 months of treatment, morphological, functional and biochemical analyses were performed. MI induced structural and functional changes in the left ventricle with worsening systolic and diastolic function, and SM supplementation at different doses did not influence these variables as analysed by echocardiography and an isolated heart study (P > .05). However, SM supplementation attenuated cardiac remodelling after MI, reducing fibrosis (P = .047) and hypertrophy (P = .006). Biomarkers of oxidative stress, inflammatory processes and energy metabolism were further investigated in the myocardial tissue. SM supplementation improved the efficiency of energy metabolism and decreased lipid hydroperoxide in the myocardium [group S (n = 8): 267.26 ± 20.7; group MI (n = 8): 330.14 ± 47.3; group MIS100 (n = 8): 313.8 ± 46.2; group MIS250: 294.3 ± 38.0 nmol/mg tissue; P = .032], as well as decreased the activation of the inflammatory pathway after MI. In conclusion, SM supplementation attenuated cardiac remodelling processes after MI. We also found that energy metabolism, oxidative stress and inflammation are associated with this effect. In addition, SM supplementation at the highest dose is more effective.

Euterpe Oleracea Mart. (Açaí) Reduces Oxidative Stress and Improves Energetic Metabolism in Myocardial Ischemia-Reperfusion Injury in Rats / Euterpe Oleracea Mart. (Açaí) Reduz o Estresse Oxidativo e Melhora o Metabolismo Energético da Lesão de Isquemia-Reperfusão Miocárdica Em Ratos

Abstract Background: Euterpe oleracea Mart. (açaí) is a fruit with high antioxidant capacity and could be an adjuvant strategy to attenuate ischemia-reperfusion injury. Objective: To evaluate the influence of açaí in global ischemia-reperfusion model in rats. Methods: Wistar rats were assigned to 2 groups: Control (C: receiving standard chow; n = 9) and Açaí (A: receiving standard chow supplemented with 5% açaí; n = 10). After six weeks, the animals were subjected to the global ischemia-reperfusion protocol and an isolated heart study to evaluate left ventricular function. Level of significance adopted: 5%. Results: There was no difference between the groups in initial body weight, final body weight and daily feed intake. Group A presented lower lipid hydroperoxide myocardial concentration and higher catalase activity, superoxide dismutase and glutathione peroxidase than group C. We also observed increased myocardial activity of b-hydroxyacyl coenzyme-A dehydrogenase, pyruvate dehydrogenase, citrate synthase, complex I, complex II and ATP synthase in the A group as well as lower activity of the lactate dehydrogenase and phosphofructokinase enzymes. The systolic function was similar between the groups, and the A group presented poorer diastolic function than the C group. We did not observe any difference between the groups in relation to myocardial infarction area, total and phosphorylated NF-kB, total and acetylated FOXO1, SIRT1 and Nrf-2 protein expression. Conclusion: despite improving energy metabolism and attenuating oxidative stress, açai supplementation did not decrease the infarcted area or improve left ventricular function in the global ischemia-reperfusion model.

Resumo Fundamento: Euterpe oleracea Mart. (açaí) é uma fruta com alta capacidade antioxidante e pode ser uma estratégia adjuvante para atenuar a lesão de isquemia-reperfusão. Objetivo: Avaliar a influência do açaí no modelo global de isquemia-reperfusão em ratos. Metodologia: Ratos Wistar foram divididos em 2 grupos: Controle (C: recebendo ração padrão; n = 9) e Açaí (A: recebendo ração padrão suplementada com 5% de açaí; n = 10). Após seis semanas, os animais foram submetidos ao protocolo global de isquemia-reperfusão e a estudo do coração isolado para avaliar a função ventricular esquerda. Nível de significância adotado: 5%. Resultados: Não houve diferença entre os grupos quanto ao peso corporal inicial e final, e a ingestão diária de ração. O grupo A apresentou menor concentração miocárdica de hidroperóxido lipídico e maior atividade de catalase, superóxido dismutase e glutationa peroxidase do que o grupo C. Também observamos aumento da atividade miocárdica da b-hidroxiacil coenzima-A desidrogenase, piruvato desidrogenase, citrato sintase, complexo I, complexo II e ATP sintase no grupo A, bem como menor atividade das enzimas lactato desidrogenase e fosfofructoquinase. A função sistólica foi semelhante entre os grupos, e o grupo A apresentou função diastólica pior que C. Não foram observadas diferenças entre os grupos em relação à área de infarto do miocárdio, e expressão proteica de NF-kB total e fosforilado, e das proteínas FOXO1, SIRT1 e Nrf-2. Conclusão: apesar de melhorar o metabolismo energético e atenuar o estresse oxidativo, a suplementação de açaí não diminuiu a área infartada nem melhorou a função ventricular esquerda no modelo global de isquemia-reperfusão.

Euterpe oleracea Mart. (Açai) Supplementation Attenuates Acute Doxorubicin-Induced Cardiotoxicity in Rats.

BACKGROUND/AIMS: Doxorubicin, a chemotherapy drug used successfully for years, could induce cardiotoxicity. Euterpe oleracea Mart. (açai) is a fruit high in antioxidant properties. The aim of this study was to evaluate doxorubicin-induced cardiotoxicity prevention after açai administration. METHODS: A total of 64 male Wistar rats were allocated into 4 groups: control (C), açai (A), doxorubicin (D) and açai-doxorubicin (DA). Rats received regular chow (C and D groups) or chow supplemented with açai 5% (A and DA groups) for 4 weeks. Subsequently, rats received doxorubicin 20 mg/kg (D and DA groups) or saline (C and A groups). Euthanasia was performed 48 hours after doxorubicin injection. Left ventricular function was evaluated by echocardiography in vivo and by isolated heart study ex vivo. Oxidative stress, myocardial metabolism and nitric oxide metabolite were evaluated by spectrophotometry, MMP-2 activity by zymography and caspase-3 and Bcl-2 protein expression by Western blot. RESULTS: Doxorubicin induced decreases in body weight, food and water ingestion. We observed decreases in left ventricular fractional shortening in rats treated with doxorubicin. Additionally, the same rats showed lower +dP/dt and -dP/dt during isolated heart study than those who did not receive doxorubicin. Doxorubicin injection increased caspase-3 protein expression, myocardium lipid hydroperoxide concentration, MMP-2 activity, phosphofructokinase and lactate dehydrogenase activity, and decreased ß-hydroxyacyl-CoA dehydrogenase, pyruvate dehydrogenase, citrate synthase, complex I, complex II and ATP synthase activity in myocardium. Açai supplementation improved left ventricular fractional shortening, decreased myocardium lipid hydroperoxide concentration, MMP-2 activity, and improved ß-hydroxyacyl-CoA dehydrogenase, phosphofructokinase, citrate synthase, complex II and ATP synthase enzymatic activities. We did not observe differences in nitric oxide metabolite concentrations between groups. CONCLUSION: Doxorubicin induced left ventricular dysfunction, increases in oxidative stress, changes in myocardium metabolism and MMP-2 activation. Açai supplementation was able to prevent these alterations.

Performance of cardiovascular risk scores in mortality prediction ten years after Acute Coronary Syndromes

SUMMARY BACKGROUND The objective of this study was to evaluate the performance of the Framingham risk score (FRS) and risk score by the American College of Cardiology/American Heart Association (SR ACC/AHA) in predicting mortality of patients ten years after acute coronary syndrome (ACS). METHODS This is a retrospective cohort study that included patients aged ≥ 18 years with ACS who were hospitalized at the Coronary Intensive Care Unit (ICU) of the Botucatu Medical School Hospital from January 2005 to December of 2006. RESULTS A total of 447 patients were evaluated. Of these, 118 were excluded because the mortality in 10 years was not obtained. Thus, 329 patients aged 62.9 ± 13.0 years were studied. Among them, 58.4% were men, and 44.4% died within ten years of hospitalization. The median FRS was 16 (14-18) %, and the ACC/AHA RS was 18.5 (9.1-31.6). Patients who died had higher values of both scores. However, when we classified patients at high cardiovascular risk, only the ACC/AHA RS was associated with mortality (p <0.001). In the logistic regression analysis, both scores were associated with mortality at ten years (p <0.001). CONCLUSIONS Both FRS and SR ACC/AHA were associated with mortality. However, for patients classified as high risk, only the ACC/AHA RS was associated with mortality within ten years.

RESUMO OBJETIVO Avaliar a performance do escore de risco de Framingham (ERF) e do escore proposto pela American College of Cardiology/American Heart Association (ER ACC/AHA) em predizer a mortalidade em pacientes dez anos após síndrome coronariana aguda (SCA). MÉTODOS Trata-se de um estudo de coorte retrospectivo que incluiu pacientes com idade ≥18 anos, com SCA, que estiveram internados na Unidade de Terapia Intensiva Coronariana (UTI) do Hospital das Clínicas de Botucatu, no período de janeiro de 2005 a dezembro de 2006. RESULTADOS Foram avaliados 447 pacientes. Destes, 118 foram excluídos, pois a mortalidade em dez anos não foi obtida. Logo, 329 pacientes com idade de 62,9±13,0 anos foram estudados. Dentre eles, 58,4% eram homens e 44,4% morreram no período de dez anos após a internação. A mediana do ERF foi de 16 (14-18)%, e do ER ACC/AHA foi 18,5 (9,1-31,6)%. Os pacientes que evoluíram a óbito apresentaram maiores valores dos escores. No entanto, quando classificamos os pacientes em alto risco cardiovascular, apenas o ER ACC/AHA foi associado com a mortalidade (p<0,001). Na análise de regressão logística, ambos os escores foram associados com a mortalidade em dez anos (p<0,001). CONCLUSÕES Tanto o ERF quanto o ER ACC/AHA foram associados com a mortalidade. No entanto, para os pacientes classificados como alto risco, apenas o ER ACC/AHA foi associado com a mortalidade em dez anos.

Lipid damage is the best marker of oxidative injury during the cardiac remodeling process induced by tobacco smoke.

BACKGROUND: Oxidative stress is one potential mechanism that explain the direct effects of smoking on cardiac remodeling process. However, no study has compared different myocardial products of macromolecule oxidation after tobacco smoke exposure. Thus, the aim of this study was to investigate the lipid hydroperoxide (LH) levels, protein carbonyl concentrations and DNA damage in cardiac tissue of rats exposed to tobacco smoke. METHODS: Male Wistar rats were divided into two groups: group C (control, n = 14) composed of animals not exposed to cigarette smoke; group ETS (exposed to tobacco smoke, n = 14) composed by animals exposed to cigarette smoke. The animals were exposed to 2 month of ETS and morphological, biochemical and functional analyses were performed. RESULTS: Cardiac cotinine levels were elevated in the ETS group. In addition, the myocyte cross-sectional area was higher in the ETS group. (C = 266.6 ± 23.2 µm2 and ETS = 347.5 ± 15.1 µm2, p <  0.001). Cardiac LH was higher in the ETS group than in group C (C = 196.4 ± 51.5 nmol/g and ETS = 331.9 ± 52.9 nmol/g, p <  0.001). However, there were no between-group differences in cardiac protein carbonyl concentration or DNA damage. CONCLUSIONS: Therefore, our results suggest that, in this model, lipid damage is a good marker of oxidative damage during the cardiac remodeling process induced by 2 months of exposure to tobacco smoke.

Spondias mombin supplementation attenuated cardiac remodelling process induced by tobacco smoke.

The objective of this study was to investigate the influence of Spondias mombin (SM) supplementation on the cardiac remodelling process induced by exposure to tobacco smoke (ETS) in rats. Male Wistar rats were divided into 4 groups: group C (control, n = 20) comprised animals not exposed to cigarette smoke and received standard chow; group ETS (n = 20) comprised animals exposed to cigarette smoke and received standard chow; group ETS100 (n = 20) received standard chow supplemented with 100 mg/kg body weight/d of SM; and group ETS250 (n = 20) received standard chow supplemented with 250 mg/kg body weight/d of SM. The observation period was 2 months. The ETS animals had higher values of left cardiac chamber diameters and of left ventricular mass index. SM supplementation attenuated these changes. In addition, the myocyte cross-sectional area (CSA) was lower in group C compared with the ETS groups; however, the ETS250 group had lower values of CSA compared with the ETS group. The ETS group also showed higher cardiac levels of lipid hydroperoxide (LH) compared with group C; and, groups ETS100 and ETS250 had lower concentrations of LH compared with the ETS group. Regarding energy metabolism, SM supplementation decreased glycolysis and increased the ß-oxidation and the oxidative phosphorylation. There were no differences in the expression of Nrf-2, SIRT-1, NF-κB, interferon-gamma and interleukin 10. In conclusion, our results suggest that ETS induced the cardiac remodelling process. In addition, SM supplementation attenuated this process, along with oxidative stress reduction and energy metabolism modulation.

Phase angle is associated with the length of ICU stay in patients with non-ST elevation acute coronary syndrome

Background: The aim of this study was to evaluate the associations between phase angle (PhA), sarcopenia, and the length of stay (LOS) in the coronary intensive care unit (ICU) in patients with non-ST acute coronary syndrome(NSTE-ACS).Methods: This was a prospective observational study that evaluated 80 patients with NSTE-ACS over the age of18 years, admitted to the ICU from January to June 2014. Upon admission, the patients'demographic information was recorded. Handgrip strength and bioelectrical impedance analysis (BIA) were performed, and blood samples were taken within the first 72 h of admission. All of the patients were followed during their ICU stays. Results: We evaluated 80 patients, five were excluded due to impossibility of assessing handgrip strength, and seven patients were not subjected to BIA. Thus, 68 patients with a mean age of 63.3 ± 13.1 years were included in the analysis. Among these patients, 60.1% were male, 27.9% of the patients had sarcopenia, 8.8% had LOSs≥8 days, and median phase angle was 6.5 (6.1­7.3)°. Multiple logistic regression adjusted for age and gender revealed tha PhA was not associated with the presence of sarcopenia. Additionally, PhA (OR 0.337; CI 95% 0.118­0.961;p= 0.04)but not sarcopenia (OR 0.517; CI 95% 0.055­4.879;p= 0.56) was associated with an increased LOS. Conclusions: PhA is associated with LOS in patients with NSTE-ACS. Additionally, there was no association between PhA and sarcopenia.

Impact of coronary intensive care unit in treatment of myocardial infarction / Impacto da unidade coronariana no tratamento do infarto do miocárdio

Summary Introduction: The mortality rate attributed to ST-segment elevation myocardial infarction (STEMI) has decreased in the world. However, this disease is still responsible for high costs for health systems. Several factors could decrease mortality in these patients, including implementation of cardiac intensive care units (CICU). The aim of this study was to evaluate the effect of CICU implementation on prescribed recommended treatments and mortality 30 days after STEMI. Method: We performed a retrospective study with patients admitted to CICU between 2005 and 2006 (after group) and between 2000 and 2002, before CICU implementation (before group). Results: The after group had 101 patients, while the before group had 143 patients. There were no differences in general characteristics between groups. We observed an increase in angiotensin-converting enzyme inhibitors, clopidogrel and statin prescriptions after CICU implementation. We did not find differences regarding number of patients submitted to reperfusion therapy; however, there was an increase in primary percutaneous angioplasty compared with thrombolytic therapy in the after group. There was no difference in 30-day mortality (before: 10.5%; after: 8.9%; p=0.850), but prescription of recommended treatments was high in both groups. Prescription of angiotensin-converting enzyme inhibitors and beta-blocker decreased mortality risk by 4.4 and 4.9 times, respectively. Conclusion: CICU implementation did not reduce mortality after 30 days in patients with STEMI; however, it increased the prescription of standard treatment for these patients.

Resumo Introdução: Apesar da diminuição da mortalidade por infarto agudo do miocárdio com supradesnivelamento do segmento ST (IAM-ST) no mundo, a doença ainda acarreta elevados custos e morbidade. Muitas medidas contribuem para a redução da mortalidade, dentre elas a criação de unidades intensivas coronarianas (UCO). Objetivo: Avaliar o impacto da criação de uma UCO na prescrição de tratamentos preconizados e na mortalidade em 30 dias em pacientes com IAM-ST. Método: Foi realizado estudo retrospectivo e foram coletados dados de prontuários de pacientes internados na UCO de 2005 a 2006 (grupo depois). Esses dados foram comparados com dados do serviço de 2000 a 2002, previamente à criação da UCO (grupo antes). Resultados: Havia 101 e 143 pacientes nos grupos depois e antes, respectivamente. Não houve diferenças em relação às características populacionais e às características do infarto entre os períodos. Observamos aumento na prescrição de iECA, clopidogrel e estatinas. Apesar da ausência de mudanças no número de pacientes que receberam terapia de reperfusão, houve aumento de angioplastias primárias em detrimento ao uso de trombolíticos no período posterior à criação da UCO. Não observamos diminuição da mortalidade em 30 dias após IAM-ST (antes: 10,5%; depois: 8,9%; p=0,850), mas a prescrição de tratamentos preconizados foi alta em ambos os períodos. O uso de iECA e de betabloqueador diminuiu o risco de morte em 4,4 e 4,9 vezes, respectivamente. Conclusão: Em pacientes com IAM-ST, a criação da UCO não reduziu a mortalidade em 30 dias, mas houve aumento na prescrição de tratamentos preconizados.

Vitamin D role in smoking women and cardiac remodeling

Background: The objective of the study is to evaluate the influence of serum vitamin D concentrations and smoking status in cardiac structure and function. Methods: The participants of this study were healthy women smokers (n = 18, mean age 52.8 years), ex-smokers ( n = 18, mean age 51.7 years), and never smokers ( n = 19, mean age 44.4 years). All participants underwent assessment of body composition, dietary intake, sun exposure frequency, vitamin D serum determination, and echocardiographic assessment. All data underwent statistical analysis. Results: The three groups were classified as overweight. The group of ex-smokers showed significantly higher vitamin D serum concentrations. Smoker group showed a higher posterior wall thickness (PW), left ventricular mass, and left ventricular mass index (LVMI). We identified positive correlations between LVMI and smoking history, PW and vitamin D serum, and body mass index and time of smoking history. Multiple linear regressions showed positive association of smoking history and LVMI and PW, also that serum vitamin D has a positive association with PW. PW was associated with smoking history and serum vitamin D, showing a deleterious effect on the heart of both variables. Conclusions: Smoking habit in adult women was associated with cardiac remodeling, and excess of vitamin Dis associated with the action of smoking on cardiac variables. Thus, higher serum vitamin D values have a deleterious effect on the heart in this model.

Erythrocyte superoxide dismutase as a biomarker of septic acute kidney injury.

BACKGROUND: Oxidative stress is a key feature of sepsis and could be a common pathophysiological pathway between septic shock and acute kidney injury (AKI) Our objective was to evaluate the erythrocyte superoxide dismutase (SOD1) activity as predictor of AKI in patients with septic shock. METHODS: This is a prospective observational study that evaluated 175 consecutive patients over the age of 18 years with septic shock upon intensive care unit (ICU) admission. However, 43 patients were excluded (27 due to AKI at ICU admission). Thus, 132 patients were enrolled in the study. At the time of the patients' enrollment, demographic information was recorded. Blood samples were taken within the first 24 h of the patient's admission to determine the erythrocyte SOD1 activity. All patients were followed throughout the ICU stay, and the development of AKI was evaluated. In addition, we also evaluated 17 control subjects. RESULTS: The mean age of patients with septic shock was 63.2 ± 15.7 years, 53 % were male and the median ICU stay was 8 days (4-16). Approximately 50.7 % developed AKI during the ICU stay. The median erythrocyte SOD1 activity was 2.92 (2.19-3.92) U/mg Hb. When compared to control subjects, septic shock patients had a higher serum malondialdehyde concentration and lower erythrocyte SOD1 activity. In univariate analysis, erythrocyte SOD1 activity was lower in patients who developed AKI. The ROC curve analysis revealed that lower erythrocyte SOD1 activity was associated with AKI development (AUC 0.686; CI 95 % 0.595-0.777; p < 0.001) at the cutoff of <3.32 U/mg Hb. In the logistic regression models, SOD1 activity higher than 3.32 U/mg Hb was associated with protection of AKI development when adjusted by hemoglobin, phosphorus and APACHE II score (OR 0.309; CI 95 % 0.137-0.695; p = 0.005) and when adjusted by age, gender, chronic kidney disease, admission category (medical or surgery) and APACHE II score (OR 0.129; CI 95 % 0.033-0.508; p = 0.003). CONCLUSIONS: In conclusion, our data suggest that erythrocyte SOD1 activity could play a role as an early marker of septic AKI and could be seen as a new research avenue in the field of biomarker in AKI. However, our study did not show a strong correlation between SOD activity and AKI. Nevertheless, these original data do warrant further research in order to confirm or not this hypothesis.

Acute doxorubicin-induced cardiotoxicity is associated with matrix metalloproteinase-2 alterations in rats.

BACKGROUND: Doxorubicin can cause cardiotoxicity. Matrix metalloproteinases (MMP) are responsible for degrading extracellular matrix components which play a role in ventricular dilation. Increased MMP activity occurs after chronic doxorubicin treatment. In this study we evaluated in vivo and in vitro cardiac function in rats with acute doxorubicin treatment, and examined myocardial MMP and inflammatory activation, and gene expression of proteins involved in myocyte calcium transients. METHODS: Wistar rats were injected with doxorubicin (Doxo, 20 mg/kg) or saline (Control). Echocardiogram was performed 48 h after treatment. Myocardial function was assessed in vitro in Langendorff preparation. RESULTS: In left ventricle, doxorubicin impaired fractional shortening (Control 0.59 ± 0.07; Doxo 0.51 ± 0.05; p < 0.001), and increased isovolumetric relaxation time (Control 20.3 ± 4.3; Doxo 24.7 ± 4.2 ms; p = 0.007) and myocardial passive stiffness. MMP-2 activity, evaluated by zymography, was increased in Doxo (Control 141338 ± 8924; Doxo 188874 ± 7652 arbitrary units; p < 0.001). There were no changes in TNF-α, INF-γ, IL-10, and ICAM-1 myocardial levels. Expression of phospholamban, Serca-2a, and ryanodine receptor did not differ between groups. CONCLUSION: Acute doxorubicin administration induces in vivo left ventricular dysfunction and in vitro increased myocardial passive stiffness in rats. Cardiac dysfunction is related to myocardial MMP-2 activation. Increased inflammatory stimulation or changed expression of the proteins involved in intracellular calcium transients is not involved in acute cardiac dysfunction.