Electrospinning of Hyperbranched Poly-L-Lysine/Polyaniline Nanofibers for Application in Cardiac Tissue Engineering

Electrospun polyaniline nanofibers are one of the most promising materials for cardiac tissue engineering due to their tunable electroactive properties. Moreover, the biocompatibility of polyaniline nanofibes can be improved by grafting of adhesive peptides during the synthesis. In this paper, we describe the biocompatible properties and cardiomyocytes proliferation on polyaniline electrospun nanofibers modified by hyperbranched poly-L-lysine dendrimers (HPLys). The microstructure characterization of the HPLys/polyaniline nanofibers was carried out by scanning electron microscopy (SEM). It was observed that the application of electrical current stimulates the differentiation of cardiac cells cultured on the nanofiber scaffolds. Both electroactivity and biocompatibility of the HPLys based nanofibers suggest the use this material for culture of cardiac cells and opens the possibility of using this material as a biocompatible electroactive 3-D matrix in cardiac tissue engineering.

Nicorandil protects cardiac mitochondria against permeability transition induced by ischemia-reperfusion

Ischemia followed by reperfusion is known to negatively affect mitochondrial function by inducing a deleterious condition termed mitochondrial permeability transition. Mitochondrial permeability transition is triggered by oxidative stress, which occurs in mitochondria during ischemia-reperfusion as a result of lower antioxidant defenses and increased oxidant production. Permeability transition causes mitochondrial dysfunction and can ultimately lead to cell death. A drug able to minimize mitochondrial damage induced by ischemia-reperfusion may prove to be clinically effective. We aimed to analyze the effects of nicorandil, an ATP-sensitive potassium channel agonist and vasodilator, on mitochondrial function of rat hearts and cardiac HL-1 cells submitted to ischemia-reperfusion. Nicorandil decreased mitochondrial swelling and calcium uptake. It also decreased reactive oxygen species formation and thiobarbituric acid reactive substances levels, a lipid peroxidation biomarker. We thus confirm previous reports that nicorandil inhibits mitochondrial permeability transition and demonstrate that nicorandil inhibits this process by preventing oxidative damage and mitochondrial calcium overload induced by ischemia-reperfusion, resulting in improved cardiomyocyte viability. These results may explain the good clinical results obtained when using nicorandil in the treatment of ischemic heart disease.

Comparison between two methods for cardiac output measurement in propofol-anesthetized dogs: thermodilution and Doppler

ObjectiveTo compare cardiac output (CO) measured by Doppler echocardiography and thermodilution techniques in spontaneously breathing dogs during continuous infusion of propofol. To do so, CO was obtained using the thermodilution method (CO(TD)) and Doppler evaluation of pulmonary flow (CO(DP)) and aortic flow (CO(DA)).Study designProspective cohort study.AnimalsEight adult dogs weighing 8.3 +/- 2.0 kg.MethodsPropofol was used for induction (7.5 +/- 1.9 mg kg-1 IV) followed by a continuous rate infusion at 0.7 mg kg-1 minute-1. The animals were positioned in left lateral recumbency on an echocardiography table that allowed for positioning of the transducer at the 3rd and 5th intercostal spaces of the left hemithorax for Doppler evaluation of pulmonary and aortic valves, respectively. CO(DP) and CO(DA) were calculated from pulmonary and aortic velocity spectra, respectively. A pulmonary artery catheter was inserted via the jugular vein and positioned inside the lumen of the pulmonary artery in order to evaluate CO(TD). The first measurement of CO(TD), CO(DP) and CO(DA) was performed 30 minutes after beginning continuous infusion (T0) and then at 15-minute intervals (T15, T30, T45 and T60). Numeric data were submitted to two-way anova for repeated measurements, Pearson's correlation coefficient and Bland & Altman analysis. Data are presented as mean +/- SD.ResultsAt T0, CO(TD) was lower than CO(DA). CO(DA) was higher than CO(TD) and CO(DP) at T30, T45 and T60. The difference between the CO(TD) and CO(DP), when all data were included, was -0.04 +/- 0.22 L minute-1 and Pearson's correlation coefficient (r) was 0.86. The difference between the CO(TD) and CO(DA) was -0.87 +/- 0.54 L minute-1 and r = 0.69. For CO(TD) and CO(DP), the difference was -0.82 +/- 0.59 L minute-1 and r = 0.61.ConclusionDoppler evaluation of pulmonary flow was a clinically acceptable method for assessing the CO in propofol-anesthetized dogs.

Cardiac function in dogs with chronic Chagas cardiomyopathy undergoing autologous stem cell transplantation into the coronary arteries

This study assessed the effects of a single intracoronary injection of autologous stem cells on the cardiac function of dogs with Chagas cardiomyopathy. Bone-marrow-derived stem cells were delivered into the right and left coronary arteries of 5 mature dogs with mildly compromised cardiac function due to chronic Chagas cardiomyopathy. Blood pressure and electrocardiographic and echocardiographic parameters were recorded at monthly intervals for 6 mo in the 3 dogs that survived. Although no changes were observed in the electrocardiogram and blood pressure, there was a significant increase in peak velocity of aortic flow 3 mo after stem cell transplantation. Pre-ejection period, isovolumic relaxation time, and the Tei index of myocardial performance were reduced significantly 4 mo after the procedure. All significant changes persisted to the end of the study. The results suggest that the transplantation of autologous bone-marrow-derived stem cells into the coronary arteries of dogs with Chagas cardiomyopathy may have a beneficial effect but the small number of dogs studied was a limitation.

Effects of weight loss on the cardiac parameters of obese dogs

A obesidade é uma das doenças nutricionais mais frequentemente observada em cães e pode provocar sérios problemas de saúde, como os distúrbios cardiovasculares. Realizou-se este estudo visando avaliar algumas das possíveis alterações estruturais e funcionais cardíacas decorrentes da correção da obesidade canina. Para isso foram utilizados 18 cães obesos divididos pelo peso corporal em Grupo I (até 15kg), Grupo II (entre 15,1 e 30 kg) e Grupo III (acima de 30 kg). Os animais foram submetidos à restrição calórica de forma a perderem 15% do peso vivo. Foram realizados os exames ecocardiográfico em modo-M, eletrocardiográfico e mensuração da pressão arterial dos animais antes do início do tratamento da obesidade e após atingirem o peso meta. Os resultados revelaram que após a redução de peso ocorreram diminuições significativas da espessura da parede livre do ventrículo esquerdo durante a sístole e diástole no Grupo III, diminuição da pressão arterial sistólica no Grupo III e também da pressão arterial média no Grupo II. Assim, concluiu-se que a perda de peso pode reverter as alterações estruturais cardíacas, como a hipertrofia excêntrica do ventrículo esquerdo em cães obesos acima de 30 kg, como também reduzir a pressão arterial sistêmica em cães obesos submetidos à restrição calórica mediante administração de dieta hipocalórica.

Sexing of murine and bovine embryos by developmental high-titer arrest induced by H-Y antisera

Murine and bovine embryos at the late morula stage were cultured in medium containing high-titer rat H-Y antisera. After 12 h of incubation, embryos blocked at the late morulae stage were classified as males and those at the blastocyst stage were classified as females. Sexing of murine embryos by PCR and cytogenetics revealed that 83% of the embryos classified as males and 82% of those classified as females had their sex correctly predicted (P < 0.05). Bovine embryos were transferred to recipient females. Pregnancy rates were 71.4% (10/14) for embryos classified as males and 68.8% (11/16) for embryos classified as females. The sex was correctly predicted for 80% (8/10) of the embryos classified as males and for 81.8% (9/11) of those classified as females (overall accuracy, 80.9%, P < 0.05). Therefore, the induction of developmental arrest by high-titer male-specific antisera was an efficient strategy for non-invasive embryo sexing. The procedure was straightforward and has considerable commercial potential for sexing bovine embryos. (c) 2004 Elsevier B.V. All rights reserved.

Venous tone and cardiac function in the South American rattlesnake Crotalus durissus: mean circulatory filling pressure during adrenergic stimulation in anaesthetised and fully recovered animals

The effects of adrenergic stimulation on mean circulatory filling pressure (MCFP), central venous pressure (P-CV) and stroke volume (Vs), as well as the effects of altered MCFP through changes of blood volume were investigated in rattlesnakes (Crotalus durissus). MCFP is an estimate of the upstream pressure driving blood towards the heart and is determined by blood volume and the activity of the smooth muscle cells in the veins (venous tone). MCFP can be determined as the plateau in P-CV during a total occlusion of blood flow from the heart.Vs decreased significantly when MCFP was lowered by reducing blood volume in anaesthetised snakes, whereas increased MCFP through infusion of blood (up to 3 ml kg(-1)) only led to a small rise in Vs. Thus, it seems that end-diastolic volume is not affected by an elevated MCFP in rattlesnakes. To investigate adrenergic regulation on venous tone, adrenaline as well as phenylephrine and isoproterenol (alpha- and beta-adrenergic agonists, respectively) were infused as bolus injections (2 and 10 mu g kg(-1)). Adrenaline and phenylephrine caused large increases in MCFP and P-CV, whereas isoproterenol decreased both parameters. This was also the case in fully recovered snakes. Therefore, adrenaline affects venous tone through both alpha- and beta-adrenergic receptors, but the alpha-adrenergic receptor dominates at the dosages used in the present study. Injection of the nitric oxide donor SNP caused a significant decrease in P-CV and MCFP. Thus, nitric oxide seems to affect venous tone.

Analysis of cardiac autonomic modulation in obese and eutrophic children

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Energy Expenditure, Lipid Profile, Oxidative Stress, and Cardiac Energy Metabolism After Growth Hormone Treatment in Obese Young Rats

Obesity is rampant in modern society and growth hormone (GH) could be useful as adjunct therapy to reduce the obesity-induced cardiovascular damage. To investigate GH effects on obesity, initially 32 male Wistar rats were divided into two groups (n = 16): control (C) was fed standard-chow and water and hyper-caloric (H) was fed hypercaloric chow and 30% sucrose in its drinking water. After 45 days, both C and H groups were divided into two subgroups (n = 8): C + PL was fed standard-chow, water and received saline subcutaneously; C + GH was fed standard-chow, water, and received 2 mg/kg/day GH subcutaneously; H + PL was fed hypercaloric diet, 30% sucrose in its drinking water, and received saline subcutaneously; and H + GH was fed hypercaloric diet, 30% sucrose in its drinking water, and received GH subcutaneously. After 75 days of total experimental period, H + PL rats were considered obese, having higher body weight, body mass index, Lee-index, and atherogenic index (AI) compared to C + PL. Obesity was accompanied by enhanced myocardial lipid hydroperoxide (LH) and lactate dehydrogenase (LDH), as well of depressed energy expenditure (RMR) and oxygen consumption(VO(2))/body weight. H + GH rats had higher fasting RMR, as well as lower AI and myocardial LH than H + PL. Comparing C + GH with C + PL, despite no effects on morphometric parameters, lipid profile, myocardial LH, and LDH activity, GH enhanced fed RMR and myocardial pyruvate dehydrogenase. In conclusion, the present study brought new insights into the GH effects on obesity related cardiovascular damage demonstrating, for the first time, that GH regulated cardiac metabolic pathways, enhanced energy expenditure and improved the lipid profile in obesity condition. Growth hormone in standard fed condition also offered promising therapeutic value enhancing pyruvate-dehydrogenase activity and glucose oxidation in cardiac tissue, thus optimizing myocardial energy metabolism.

Cell cycle arrest evidence, parasiticidal and bactericidal properties induced by L-amino acid oxidase from Bothrops atrox snake venom

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Presence of autoantibodies against HeLa small nuclear ribonucleoproteins in chagasic and non-chagasic cardiac patients

We detected anti-human small nuclear ribonucleoprotein (snRNP) autoantibodies in chagasic patients by different immunological methods using HeLa snRNPs. ELISA with Trypanosoma cruzi total lysate antigen or HeLa human U small nuclear ribonucleoproteins (UsnRNPs) followed by incubation with sera from chronic chagasic and non-chagasic cardiac patients was used to screen and compare serum reactivity. Western blot analysis using a T. cruzi total cell extract was also performed in order to select some sera for Western blot and immunoprecipitation assays with HeLa nuclear extract. ELISA showed that 73 and 95% of chronic chagasic sera reacted with HeLa UsnRNPs and T. cruzi antigens, respectively. The Western blot assay demonstrated that non-chagasic cardiac sera reacted with high molecular weight proteins present in T. cruzi total extract, probably explaining the 31% reactivity found by ELISA. However, these sera reacted weakly with HeLa UsnRNPs, in contrast to the chagasic sera, which showed autoantibodies with human Sm (from Stefanie Smith, the first patient in whom this activity was identified) proteins (B/B', D1, D2, D3, E, F, and G UsnRNP). Immunoprecipitation reactions using HeLa nuclear extracts confirmed the reactivity of chagasic sera and human UsnRNA/RNPs, while the other sera reacted weakly only with U1snRNP. These findings agree with previously reported data, thus supporting the idea of the presence of autoimmune antibodies in chagasic patients. Interestingly, non-chagasic cardiac sera also showed reactivity with T. cruzi antigen and HeLa UsnRNPs, which suggests that individuals with heart disease of unknown etiology may develop autoimmune antibodies at any time. The detection of UsnRNP autoantibodies in chagasic patients might contribute to our understanding of how they develop upon initial T. cruzi infection.

Auditory stimulation and cardiac autonomic regulation

Previous studies have already demonstrated that auditory stimulation with music influences the cardiovascular system. In this study, we described the relationship between musical auditory stimulation and heart rate variability. Searches were performed with the Medline, SciELO, Lilacs and Cochrane databases using the following keywords: auditory stimulation, autonomic nervous system, music and heart rate variability. The selected studies indicated that there is a strong correlation between noise intensity and vagal-sympathetic balance. Additionally, it was reported that music therapy improved heart rate variability in anthracycline-treated breast cancer patients. It was hypothesized that dopamine release in the striatal system induced by pleasurable songs is involved in cardiac autonomic regulation. Musical auditory stimulation influences heart rate variability through a neural mechanism that is not well understood. Further studies are necessary to develop new therapies to treat cardiovascular disorders.

Intraoperative lactate levels and postoperative complications of pediatric cardiac surgery

Objectives: Correlate arterial lactate levels during the intraoperative period of children undergoing cardiac surgery and the occurrence of complications in the postoperative period. Aim: Arterial lactate levels can indicate hypoperfusion states, serving as prognostic markers of morbidity and mortality in this population. Background: Anesthesia for cardiac pediatric surgery is frequently performed on patients with serious abnormal physiological conditions. During the intraoperative period, there are significant variations of blood volume, body temperature, plasma composition, and tissue blood flow, as well as the activation of inflammation, with important pathophysiological consequences. Methods/Materials: Chart data relating to the procedures and perioperative conditions of the patients were collected on a standardized form. Comparisons of arterial lactate values at the end of the intraoperative period of the patients that presented, or not, with postoperative complications and frequencies related to perioperative conditions were established by odds ratio and nonparametric univariate analysis. Results: After surgeries without cardiopulmonary bypass (CPB), higher levels of arterial lactate upon ICU admission were observed in patients who had renal complications (2.96 vs 1.31 mm) and those who died (2.93 vs 1.40 mm). For surgeries with CPB, the same association was observed for cardiovascular (2.90 mm x 2.06 mm), renal (3.34 vs 2.33 mm), respiratory (2.98 vs 2.12 mm) and hematological complications (2.99 vs 1.95 mm), and death (3.38 vs 2.40 mm). Conclusion: Elevated intraoperative arterial lactate levels are associated with a higher morbidity and mortality in low- and medium-risk procedures, with or without CPB, in pediatric cardiac surgery.