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Previous studies have suggested that the Angiotensin-(1-7) [(Ang-(1-7)] can change cardiac function by modulating the autonomic nervous system. However, it is unknown whether the Ang-(1-7) can modulate the effect of acetylcholine (ACh) in ventricular contractility. Thus, this study aimed to investigate whether Ang-(1-7) modifies the amplitude of the cardiac cholinergic effects and if these effects are intrinsic to the heart. In anesthetized Wistar rats, Ang-(1-7) attenuated the effect of ACh in decreasing the left ventricular end-systolic pressure (LVESP), dP/dt

Bombesin mediates several biological activities in the gastrointestinal (GI) tract and central nervous system in mammals, including smooth muscle contraction, secretion of GI hormones and regulation of homeostatic mechanisms. Here, we report a novel bombesin-like peptide isolated from Boana raniceps. Its amino acid sequence, GGNQWAIGHFM-NH

Our aim with this study was to evaluate the consumption, performance, quantitative characteristics of carcasses, biochemical profile, plasma levels of ghrelin and leptin, expression of the receptor for ghrelin (GHS-R1a) in the hypothalamus and duodenum, and the number of goblet cells in the duodenum of calves subjected to milk volume restriction and supplemented with 2-hydroxy-4-(methylthio)butanoic acid (HMTBa). We used 21 Holstein mixed-breed calves, aged between 3 and 15 d with an average weight of 36.8 kg, and housed in pens with troughs for hay, concentrate, and water. The study included two consecutive experimental periods (first period [P1] and second period [P2]) of 21 d each, with 7 d of adaptation to the diet and facilities. The calves were distributed in a completely randomized design in three treatments with seven repetitions. 1) Control: 6 liters of milk/d during P1 and 6 liters of milk/day during P2; 2) RES (milk restriction): 3 liters of milk/day during P1 and 6 liters of milk/day during P2; and 3) RES + HMTBa: 3 liters of milk/day during P1 and 6 liters of milk/day during P2 + 3.3 g of HMTBa/day in both periods. HMTBa was supplied in milk, and the amount of concentrated ration and hay provided and leftovers were recorded daily to estimate dry matter (DM) and crude protein consumption. Mean daily weight gain (DWG), final weight (FW), and feed conversion (FC) were obtained at the beginning and at the end of each 21-d period. Plasma concentrations of ghrelin and leptin, triglycerides, total protein, urea, lactate, creatinine, alkaline phosphatase, and cholesterol were measured for P1 and P2 at the end of each 21-d period. At the end of P2, animals were slaughtered; sections of the duodenum were collected to evaluate the expression of GHS-R1a and quantity of goblet cells; hypothalamus was used to evaluate the expression of GHS-R1a; rumen was used to evaluate the thickness of epithelium and keratin and the density, height, and width of ruminal papillae. In P1, total DM consumption, FW, DWG, glucose, and triglycerides were lower in the RES and RES + HMTBa groups (P < 0.001). In P2, there was an improvement in the FC of the RES + HMTBa group (compared with Control and RES groups) and a lower urea concentration in the RES group (compared with Control and RES + HMTBa groups) (P < 0.001). No differences were observed among groups regarding hormonal concentrations, histological parameters, and GHS-R1a expression in the duodenum and hypothalamus. Therefore, milk restriction combined with HMTBa supplementation promoted greater compensatory gain by a mechanism independent of changes in GHS-R1a expression and hormone levels of ghrelin and leptin.

Cardiovascular alterations are frequently related to epilepsy in both clinical and experimental models, and have been hypothesized as a potential contributor to sudden unexpected death in epilepsy (SUDEP). Further, the frequency of generalized tonic-clonic seizures (GTCS) is a primary risk factor for SUDEP. Therefore, we aimed to evaluate the vascular response of rats subjected to the electrical amygdala kindling model of epilepsy. Male Wistar rats were randomly distributed into the following groups: without seizures (sham, n = 8), 5 GTCS (5 S, n = 5), and 10 GTCS (10 S, n = 6). One day after the last seizure, the rats were euthanized, and the thoracic aorta rings with (E

Generalized tonic-clonic seizures (GTCS) are the main risk factor for sudden unexpected death in epilepsy (SUDEP). Also, among the several mechanisms underlying SUDEP there is the cardiac dysfunction. So, we aimed to evaluate the impact of the number of seizures on heart function and morphology in rats with epilepsy. Rats were randomized into three groups: Sham (without epilepsy), 5 S, and 10 S groups, referred as rats with epilepsy with a total of 5 or 10 GTCS, respectively. Epilepsy was induced by electrical amygdala kindling. The ventricular function was analyzed by the Langendorff technique and challenged by ischemia/reperfusion protocol. Cardiac fibrosis and hypertrophy were analyzed by histology. We also analyzed cardiac metalloproteinases (MMP2 and MMP9), ERK 1/2 and phosphorylated ERK1/2 (P-ERK) by western blot; microRNA-21 and -320 by RT-PCR; and oxidative stress (TBARS, catalase activity and nitrite) by biochemical analysis. Only the 5S group presented decreased values of ventricular function at before ischemia/reperfusion (baseline): intraventricular systolic pressure, developed intraventricular pressure, positive and negative dP/dt. During ischemia/reperfusion protocol, the variation of the ventricular function did not differ among groups. Both 5S and 10S groups had increased cardiomyocyte hypertrophy and fibrosis compared to Sham, but in the 5S group, these alterations were higher than in the 10S group. The 5S group increased in microRNA-21 and decreased in microRNA-320 expression compared to Sham and the 10S group. The 10S group increased in MMP9 and decreased in P-ERK/ERK expression, and increased in nitrite content compared to both Sham and the 5S group. Therefore, seizures impair cardiac function and morphology, probably through microRNA modulation. The continuation of seizures seems to exert a preconditioning-like stimulus that fails to compensate the cardiac tissue alteration.

Temporal lobe epilepsy (TLE) is the most frequent type of epilepsy and is often refractory to pharmacological treatment. In this scenario, extensive research has identified components of the renin–angiotensin system (RAS) as potential therapeutic targets. Therefore, the aim of the present study was to evaluate the effects of long-term treatment with angiotensin-(1-7) [Ang-(1-7)] in male Wistar rats with TLE induced by pilocarpine (PILO). Rats with TLE were submitted to intracerebroventricular (icv) infusion of Ang-(1-7) (200 ng/kg/h) for 28 days, starting at the first spontaneous motor seizure (SMS). Body weight, food intake, and SMS were evaluated daily. Behavioral tests and hippocampal protein levels were also evaluated at the end of the treatment. Ang-(1-7) treatment reduced the frequency of SMS and attenuated low anxiety levels, increased locomotion/exploration, and reduced body weight gain that was induced by TLE. Moreover, Ang-(1-7) positively regulated the hippocampal levels of antioxidant protein catalase and antiapoptotic protein B-cell lymphoma 2 (Bcl-2), as well as mammalian target of rapamycin (mTOR) phosphorylation, which were reduced by TLE. The hippocampal up-regulation of angiotensin type 1 receptor induced by TLE was also attenuated by Ang-(1-7), while the Mas receptor (MasR) was down-regulated compared with epilepsy. These data show that Ang-(1-7) presents an antiepileptic effect, increasing neuroprotection markers and reducing SMS frequency, body weight, and behavior impairments found in TLE. Therefore, Ang-(1-7) is a promising coadjutant therapeutic option for the treatment of TLE.

The effects of the renin-angiotensin system (RAS) on stem cells isolated from human dental apical papilla (SCAPs) are completely unknown. Therefore, the aim of this study was to identify RAS components expressed in SCAPs and the effects of angiotensin (Ang) II and Ang-(1-7) on cell proliferation. SCAPs were collected from third molar teeth of adolescents and maintained in cell culture. Messenger RNA expression and protein levels of angiotensin-converting enzyme (ACE), ACE2, and Mas, Ang II type I (AT1) and type II (AT2) receptors were detected in SCAPs. Treatment with either Ang II or Ang-(1-7) increased the proliferation of SCAPs. These effects were inhibited by PD123319, an AT2 antagonist. While Ang II augmented mTOR phosphorylation, Ang-(1-7) induced ERK1/2 phosphorylation. In conclusion, SCAPs produce the main RAS components and both Ang II and Ang-(1-7) treatments induced cell proliferation mediated by AT2 activation through different intracellular mechanisms.

The imbalance between antioxidant system and reactive oxygen species (ROS) generation is related to epileptogenesis, neuronal death, and seizure frequency. Treatment with vitamin E has been associated with neuroprotection and control of seizures. In most experimental studies, vitamin E treatment has short duration. Therefore, the aim of this study was to verify the role of long-term treatment with vitamin E in rats submitted to the pilocarpine model of epilepsy. Rats were divided into two main groups: control (Ctr) and pilocarpine (Pilo). Each one was subdivided according to treatment: vehicle (Ctr V and Pilo V) or vitamin E at dosages of 6 IU/kg/day (Ctr E6 and Pilo E6) or 60 IU/kg/day (Ctr E60 and Pilo E60). Treatment lasted 120 days from status epilepticus (SE). There were no statistical differences concerning treatment in the Ctr group for all variables, so the data were grouped. Carbonyl content in the hippocampus of Pilo V and Pilo E6 was higher compared with that of the Ctr group (8 ± 1.5, 7.1 ± 1, and 3.1 ± 0.3 nmol carbonyl/mg protein, respectively for Pilo V, Pilo E6, and Ctr; p 0.05). Carbonyl content was restored to control values in Pilo E60 rats (4.2 ± 1.1 and 3.1 ± 0.3 nmol carbonyl/mg protein, respectively for Pilo E60 and Ctr; p 0.05). The volume of the hippocampal formation (6.5 ± 0.3, 6.6 ± 0.4, 6.3 ± 0.3, and 7.4 ± 0.2, respectively for Pilo V, Pilo E6, Pilo E60, and Ctr) and subfields CA1 (1.6 ± 0.1, 1.4 ± 0.2, 1.5 ± 0.1, and 2 ± 0.05, respectively for Pilo V, Pilo E6, Pilo E60, and Ctr) and CA3 (1.7 ± 0.1, 1.5 ± 0.2, 1.4 ± 0.1, and 2 ± 0.1, respectively for Pilo V, Pilo E6, Pilo E60, and Ctr) was reduced in the Pilo group regardless of treatment. Parvalbumin immunostaining was increased in the hilus of the Pilo E60 group compared with that in the Ctr group (26 ± 2 and 39.6 ± 8.3 neurons, respectively for Ctr and Pilo E60). No difference was found in seizure frequency and Neo-Timm staining. Therefore, long-term treatment with 60 IU/kg/day of vitamin E prevented oxidative damage in the hippocampus and increased hilar parvalbumin expression in rats with epilepsy without a reduction in seizure frequency.

Aim: Many particularities concerning interhemispheric differences still need to be explored and unveiled. Functional and anatomical differential features found between left and right brain sides are best known as asymmetries and are consequence of the unilateral neuronal recruitment or predominance that is set to organize some function. The outflow from different neural pathways involved in the autonomic control of the cardiovascular system may route through asymmetrically relayed efferences (ipsilateral/lateralized and/or contralateral). In spite of this, the literature reporting on the role of central nuclei involved in the autonomic control is not always dedicated on these interhemispheric comparisons. Considering the recent reports demonstrating that asymmetries may set differential functional responses, it is worth checking differences between right and left sides of central regions. This review aims to inspire neuroscientists with the idea that studying the interhemispheric differences may deepen the understanding on several centrally controlled responses, with special regard to the autonomic functions underlying the cardiovascular regulation. Conclusions: Thus, an avenue of knowledge may unfold from a field of research that requires further exploration.

Prior evidence indicates that ghrelin is involved in the integration of cardiovascular functions and behavioral responses. Ghrelin actions are mediated by the growth hormone secretagogue receptor subtype 1a (GHS-R1a), which is expressed in peripheral tissues and central areas involved in the control of cardiovascular responses to stress. Aims In the present study, we assessed the role of ghrelin – GHS-R1a axis in the cardiovascular reactivity to acute emotional stress in rats. Main methods and key findings Ghrelin potentiated the tachycardia evoked by restraint and air jet stresses, which was reverted by GHS-R1a blockade. Evaluation of the autonomic balance revealed that the sympathetic branch modulates the ghrelin-evoked positive chronotropy. In isolated hearts, the perfusion with ghrelin potentiated the contractile responses caused by stimulation of the beta-adrenergic receptor, without altering the amplitude of the responses evoked by acetylcholine. Experiments in isolated cardiomyocytes revealed that ghrelin amplified the increases in calcium transient changes evoked by isoproterenol. Significance Taken together, our results indicate that the Ghrelin-GHS-R1a axis potentiates the magnitude of stress-evoked tachycardia by modulating the autonomic nervous system and peripheral mechanisms, strongly relying on the activation of cardiac calcium transient and beta-adrenergic receptors.

The aim of this study was to investigate whether treatment with diminazene aceturate (DIZE), a putative ACE2 activator, or with angiotensin-(1-7) during pregnancy could attenuate the development of cardiovascular dysfunction in the adult offspring of spontaneously hypertensive rats (SHRs). For this, pregnant SHRs received DIZE or Ang-(1-7) throughout gestation. The systolic blood pressure (SBP) was measured in the male offspring from the 6th to16th weeks of age by tail-cuff plethysmography. Thereafter, the left ventricular contractile function and coronary reactivity were evaluated by the Langendorff technique. Samples of the left ventricles (LVs) and kidneys were collected for histology and western blot assay in another batch of adult rat offspring. Maternal treatment with DIZE or Ang-(1-7) during pregnancy attenuated the increase in SBP in adult offspring. In addition, both DIZE and Ang-(1-7) treatments reduced the cardiomyocyte diameter and fibrosis deposition in the LV, and treatment with Ang-(1-7) also reduced the fibrosis deposition in the kidneys. Maternal treatment with DIZE, as well as Ang-(1-7), improved the coronary vasodilation induced by bradykinin in isolated hearts from adult offspring. However, no difference was observed in the contractile function of the LVs of these animals. The expression levels of AT1 and Mas receptors, ACE, ACE2, SOD, and catalase in the LV were not modified by maternal treatment with Ang-(1-7), but this treatment elicited a reduction in AT2 expression. These data show that treatment with DIZE or Ang-(1-7) during gestation promoted beneficial effects of attenuating hypertension and cardiac remodeling in adult offspring.

Previous studies have demonstrated a protective effect of the Ang-(1–7)/Mas receptor axis on pathological cardiac hypertrophy. Also, the involvement of Mas receptor in exercise-induced cardiac hypertrophy has been suggested. However, the role of the Ang-(1–7)/Mas receptor on pregnancy-induced cardiac remodelling remains unknown. The objective of the present study was to evaluate the participation of the Mas receptor in the development of the cardiac hypertrophy and fibrosis induced by gestation. Female Wistar rats were divided in three groups: control, pregnant and pregnant treated with Mas receptor antagonist A-779. Wild-type (WT) and Mas-knockout (KO) mice were distributed in non-pregnant and pregnant groups. Systolic blood pressure (SBP) was measured by tail-cuff plethysmography. The medial part of the left ventricle (LV) was collected for histological analysis. Echocardiographic analysis was used to evaluate cardiac function. SBP was not changed by pregnancy or A-779 treatment in the Wistar rats. Pharmacological blockade or genetic deletion of Mas receptor attenuates the pregnancy-induced myocyte hypertrophy. The treatment with A-779 or genetic deletion of the Mas receptor increased the collagen III deposition in LV from pregnant animals without changing fibroblast proliferation. KO mice presented a lower ejection fraction (EF), fractional shortening (FS) and stroke volume (SV) and higher end systolic volume (ESV) compared with WT. Interestingly, pregnancy restored these parameters. In conclusion, these data show that although Mas receptor blockade or deletion decreases physiological hypertrophy of pregnancy, it is associated with more extracellular matrix deposition. These alterations are associated with improvement of cardiac function through a Mas-independent mechanism.

Aims Angiotensin-converting enzyme 2 (ACE2) is a key modulator of the renin-angiotensin system. Recent studies have shown that diminazene aceturate (DIZE) acts as an ACE2 activator. The aim of this study was to evaluate the cardiac effects of chronic treatment with DIZE in pressure-overloaded rats. Main methods Male Wistar rats were divided into 4 groups: (1) sham; (2) aortic banded rats (AB); (3) AB + DIZE (1 mg/kg, gavage); and (4) AB + DIZE + A-779 (120 μg/day, osmotic mini-pumps). Cardiac hypertrophy was evaluated by ventricular mass index and myocyte cross-sectional area. mRNA expression of atrial natriuretic peptide (ANP), B-type natriuretic peptide (BNP) and transforming growth factor beta 1 (TGF-β) was quantified by RT-PCR. Cardiac function was assessed according to the Langendorff technique. The ACE2 and Mas protein expression was examined by western blot analysis. Key findings DIZE treatment prevented the cardiomyocyte hypertrophy promoted by AB and A-779 inhibited this effect. Also, DIZE induced the expression of ANP and BNP mRNA in cardiac tissue from AB rats and attenuated the impairment in left ventricular end-systolic pressure and left ventricular developed pressure, + dP/dt and − dP/dt caused by AB. These effects were blocked by A-779. Moreover, DIZE prevented the increase in the expression of TGF-β mRNA in AB hearts, but it did not change the ACE2 and Mas protein expression. Significance These results showed that DIZE was efficient in preventing the cardiomyocyte hypertrophy and attenuated the left ventricular contractile impairment induced by pressure overload. However, further studies are necessary to confirm whether these effects were due to ACE2 activation.

We investigated the coronary arteries reactivity alterations in rats with epilepsy induced by pilocarpine. To do so, male Wistar rats weighing between 250 g and 300 g were used. Status epilepticus (SE) was induced in rats using 385 mg/kg (i.p.) of pilocarpine. After 60 days from the first spontaneous seizure, rats were submitted to heart rate measurements and then, one day after, euthanized, and the heart was dissected and submitted to constant flow Langendorff approaches to evaluate coronary reactivity. Rats with epilepsy showed higher resting heart rate and impairment of coronary vasodilation induced by bradykinin. Endothelial nitric oxide synthase (eNOS) and superoxide dismutase (SOD) presented a reduced staining in coronary arteries, and eNOS expression was also reduced in the left ventricle of rats with epilepsy. Our findings demonstrated, for the first time, that epilepsy can cause impairment of coronary arteries reactivity, probably because of an endothelial dependent mechanism.

Sympathetic premotor neurons of the paraventricular hypothalamus (PVN) play a role in hemodynamics adjustments during changes in body fluid homeostasis. However, PVN contribution to the tonic control of cardiac function remains to be systematically studied. In this study, we assessed whether GABAergic and adrenergic synapses, known for being active in the PVN, are involved in the control of cardiac function. Adult male Wistar rats (250-350 g; n = 27) were anesthetized with urethane (1.2-1.4 g/kg i.p.) and underwent catheterization of femoral artery to record blood pressure and heart rate. The femoral vein was used to inject the vasoactive agents phenylephrine (10 μg/kg) and sodium nitroprusside (10 μg/kg) and to supplement anesthesia. The cardiac left ventricle was catheterized to record left ventricular pressure and its derivative. Craniotomy allowed for injections (100 nL) into the PVN of: muscimol (20 mM), bicuculline methiodide (0.4 mM), propranolol (10 mM), isoproterenol (100 μM), phentolamine (13 mM), phenylephrine (30 nM). We found that: (i) inhibition of PVN by muscimol, reduced arterial pressure, cardiac chronotropy and inotropy; (ii) disinhibition of PVN neurons by bicuculline evoked positive chronotropy and inotropy, and increase blood pressure; (iii) PVN alpha adrenergic receptors control cardiac chronotropy and inotropy; (iv) beta adrenergic receptors of the PVN do not influence cardiac function; (v) afterload does not contribute to the PVN-evoked inotropy. Our results indicate that the modulation of the activity of PVN neurons exerted by GABAergic and adrenergic mechanisms contribute to the control of cardiac function.

We estimated the effect of oligosaccharide supplementation and feed restriction on calves. The study was divided into two experimental periods of 28 days each with 20 crossbred calves that had initial body weight of 37 Kg and housed in individual pens. The animals were split in four experimental groups: animals fed 6 L milk/day (CON) in the two periods, animals fed milk restricted (3 L milk/day) in the first period and followed by CON feeding in the second period (RES), animals receiving supplementation of 5 g/day of mannanoligosaccharide (MOS) and animals receiving supplementation of 5 g/day mannan and frutoligosaccharide (MFOS). At the end of the study, all the animals were slaughtered. The average weight gain was lower in the restricted group when compared with CON and MFOS groups in the first period (P < 0.05) and there were no difference among the groups in the second period. Animals supplemented with MOS showed a significant increases in jejunal villus height and rumen papillae, which were not observed for MFOS group (P < 0.05) compared with RES and CON groups. There were no difference in ghrelin and leptin levels among treatments during periods 1 and 2 (P > 0.05). Also, the expression of ghrelin receptors in the paraventricular region of the hypothalamus did not differ among groups. We conclude that milk restriction during the first weeks of life in calves resulted in compensatory gain and did not modify the hormonal profile and expression of the ghrelin receptor in the hypothalamus. Moreover, a prebiotic supplementation changed the development of intestinal and ruminal epithelium.

This study investigated the influence of antihypertensive drugs, such as angiotensin-converting enzyme inhibitors (ACEIs), AT1 receptor blockers (ARBs), voltage-gated L-type calcium channel blockers, and mineralocorticoid receptor antagonists (MRAs), on the effects of angiotensin-(1-7) [Ang-(1-7)] on aorta and coronary arteries from pressure-overloaded rats. Pressure overload was induced by abdominal aortic banding (AB). To evaluate the role of antihypertensive drugs on the effect of Ang-(1-7), AB male Wistar rats weighing 250–300 g were treated with vehicle or low doses (5 mg·kg-1·day-1, gavage) of losartan, captopril, amlodipine, or spironolactone. Isolated aortic rings and isolated perfused hearts under constant flow were used to evaluate the effect of Ang-(1-7) in thoracic aorta and coronary arteries, respectively. Ang-(1-7) induced a significant relaxation in the aorta of sham animals, but this effect was reduced in the aortas of AB rats. Chronic treatments with losartan, captopril or amlodipine, but not with spironolactone, restored the Ang-(1-7)-induced aorta relaxation in AB rats. The coronary vasodilatation evoked by Ang-(1-7) in sham rats was blunted in hypertrophic rats. Only the treatment with losartan restored the coronary vasodilatory effect of Ang-(1-7) in AB rat hearts. These data support a beneficial vascular effect of an association of Ang-(1-7) and some antihypertensive drugs. Thus, this association may have potential as a new therapeutic strategy for cardiovascular diseases.

Made available in DSpace on 2018-11-26T16:33:13Z (GMT). No. of bitstreams: 0 Previous issue date: 2016-06-02 Fundacao de Amparo a Pesquisa do Estado de Goias (FAPEG) Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) Intrathecal injection of bombesin (BBS) promoted hypertensive and sympathoexcitatory effects in normotensive (NT) rats. However, the involvement of rostra' ventrolateral medulla (RVLM) in these responses is still unclear. In the present study, we investigated: (1) the effects of BBS injected bilaterally into RVLM on cardiorespiratory and sympathetic activity in NT and spontaneously hypertensive rats (SHR); (2) the contribution of RVLM BBS type 1 receptors (BB1) to the maintenance of hypertension in SHR. Urethane-anesthetized rats (1.2 g kg(-1), i.v.) were instrumented to record mean arterial pressure (MAP), diaphragm (DIA) motor, and renal sympathetic nerve activity (RSNA). In NT rats and SHR, BBS (0.3 mM) nanoinjected into RVLM increased MAP (33.9 +/- 6.6 and 37.1 +/- 4.5 mmHg, respectively; p 9 0.05) and RSNA (97.8 +/- 12.9 and 84.5 +/- 18.1%, respectively; p < 0.05). In SHR, BBS also increased DIA burst amplitude (115.3 +/- 22.7%; p 0.05). BB1 receptors antagonist (BIM-23127; 3 mM) reduced MAP (-19.9 +/- 4.4 mmHg; p < 0.05) and RSNA (-17.7 +/- 3.8%; p < 0.05) in SHR, but not in NT rats (-2.5 +/- 2.8 mmHg; -2.7 +/- 5.6%, respectively). These results show that BBS can evoke sympathoexcitatory and pressor responses by activating RVLM BB1 receptors. This pathway might be involved in the maintenance of high levels of arterial blood pressure in SHR. Univ Fed Goias, Dept Physiol Sci, Ctr Neurosci & Cardiovasc Res, Inst Biol Sci, Goiania, Go, Brazil Univ Fed Goias, Fac Pharm, Postgrad Programme Pharmaceut Sci, Goiania, Go, Brazil Univ Fed Goias, Dept Biochem & Mol Biol, Inst Biol Sci, Goiania, Go, Brazil Univ Fed Goias, Dept Morphol, Inst Biol Sci, Goiania, Go, Brazil Univ Fed Uberlandia, Dept Physiol, Coll Phys Educ, Av Engenheiro Dinz 1178,CP 593, BR-38400 Uberlandia, MG, Brazil Sao Paulo State Univ, Sch Dent, Dept Physiol & Pathol, Araraquara, Brazil Sao Paulo State Univ, Sch Dent, Dept Physiol & Pathol, Araraquara, Brazil Fundacao de Amparo a Pesquisa do Estado de Goias (FAPEG): 2012/0055431086 Fundacao de Amparo a Pesquisa do Estado de Goias (FAPEG): 2009/10267000352 CNPq: 477832/2010-5 CNPq: 483411/2012-4 CNPq: 447496/2014-0

Sudden and unexpected death in epilepsy (SUDEP) is the most common type of death among patients with epilepsy. Here, we address the importance of the experimental models in search of the mechanisms underlying SUDEP. Most studies have investigated the cardiovascular responses in animal models of epilepsy. However, there are few proposed SUDEP models in literature. Hypoventilation, apnea, respiratory distress, pulmonary hypertension, autonomic dysregulation and arrhythmia are common findings in epilepsy models. Impairments on adenosinergic and serotonergic systems, brainstem spreading depolarization, seizure-activation of neural substrates related to cardiorespiratory control, altered autonomic control, and mutations on sodium and potassium channels are hypothesis suggested. Overall, current research highlights the evident multifactorial nature of SUDEP, which involves acute and chronic aspects ranging from systemic to molecular alterations. Thus, we are convinced that elucidation and prevention of SUDEP can be achieved only through the interaction between basic and clinical science.

Embora a análise no domínio da freqüência do sinal eletromiográfico (EMG) seja empregada na caracterização do processo de fadiga muscular localizada, sua aplicação, especificamente a da freqüência mediana (Fmed), é pouco explorada no âmbito esportivo. O objetivo do presente estudo foi verificar a viabilidade da aplicação do sinal EMG, através de sua análise no domínio da freqüência, como parâmetro para determinação e diferenciação no comportamento da fadiga muscular localizada. Dois grupos de sujeitos, um caracterizado como atletas (n =12) e outro como sedentários (n =12), foram submetidos a análises baseadas em procedimentos executados em três diferentes situações experimentais, todos envolvendo a modalidade de exercício isométrico: i) teste máximo para determinação da contração isométrica voluntária máxima (CIVM); ii) teste de fadiga, sustentado por 35 seg. a 80% da CIVM; iii) teste de recuperação, sustentado por 10 seg. a 80% da CIVM; neste ultimo foi monitorado o comportamento da Fmed nos três primeiros (Fmedi) e três últimos segundos (Fmedf) do sinal EMG no músculo tibial anterior durante o teste de fadiga. Durante os 10 segundos do teste de recuperação foi calculada a Fmed referente a todo o período (Fmedr). parâmetro utilizado no cálculo do índice de recuperação muscular (IRM). Os resultados apontam que a Fmedf apresentou valor menor em relação à Fmedi em ambos os grupos (p < 0,05). Quando comparado com o grupo de sedentários, o grupo de atletas apresentou valores maiores de Fmedi e Fmedf (p < 0,05). O valor médio e desvio-padrão do IRM para o grupo de atletas foram de 62,1% ± 28,7 e, para o grupo de sedentários, de 55,2% ± 27,8 (p > 0,05). Dessa forma, os resultados apresentados neste estudo permitem inferir a viabilidade na aplicação de parâmetros no domínio da freqüência do sinal EMG para a determinação e diferenciação do comportamento da fadiga muscular localizada.Although the analysis in the frequency domain of the Electromyographic Signal (EMG) has been used in the characterization of the localized muscular fatigue process, its application, specifically the Median Frequency (MF), is rarely explored in sports. The objective of this study was to verify the viability of the EMG signal application, through its frequency domain analysis, as a parameter for determination and differentiation of the behavior of localized muscle fatigue. Two groups of subjects, one characterized as athletes (n = 12) and the other as sedentary (n = 12), were submitted to analysis based on procedures from three different experimental situations, all involving isometric exercise modality: i) maximum test for determination of the Maximum Voluntary Isometric Contraction (MVIC); ii) fatigue test, 35 sec. sustained load of 80% of MVIC; iii) recovery test, 10 sec. sustained load of 80% of MVIC. In the latter, the MF behavior in the three first (Fmedi) and three last (Fmedf) seconds of the EMG signal of tibialis anterior muscle during the fatigue test have been monitored. During the 10 seconds of the recovery test, MF was calculated regarding the whole period (Fmedr); this parameter was used to calculate the Muscular Recovery Index (MRI). The results showed that Fmedf presented lower value in relation to Fmedi in both groups (p < 0.05). Additionally, the Fmedi and Fmedf values for the athlete group were higher in comparison to the sedentary group (p < 0.05). The MRI mean value and standard deviation for the athlete group were 62.1% ± 28.7 and for the sedentary group was 55.2% ± 27.8 (p > 0.05). Therefore, the results presented in this study allow inferring the viability in the application of the frequency domain parameters of the EMG signal for the determination and differentiation of localized muscle fatigue behavior.

Social behavior depends on the integrity of social brain circuitry. The temporal lobe is an important part of the social brain, and manifests morphological and functional alterations in autism spectrum disorders (ASD). Rats with temporal lobe epilepsy (TLE), induced with pilocarpine, were subjected to a social discrimination test that has been used to investigate potential animal models of ASD, and the results were compared with those for the control group. Rats with TLE exhibited fewer social behaviors than controls. No differences were observed in nonsocial behavior between groups. The results suggest an important role for the temporal lobe in regulating social behaviors. This animal model might be used to explore some questions about ASD pathophysiology.

Approximately 1% of the population has epilepsy, the most common neurological disorder. Moreover, people with epilepsy are more likely to die prematurely than those without epilepsy, and the most common epilepsy-related category of death is sudden unexpected death in epilepsy (SUDEP). Information concerning risk factors for SUDEP is conflicting, but potential risk factors include: age, early onset of epilepsy, duration of epilepsy, uncontrolled seizures, seizure frequency, number of antiepileptic drugs and winter temperatures. Additionally, the cause of SUDEP is still unknown; however, the most commonly suggested mechanisms are cardiac abnormalities during and between seizures. This review discusses the epidemiology, risk factors, etiology, and preventative measures in the management of SUDEP.

Epilepsy is the most common neurological disorder; approximately 1% of the population worldwide have epilepsy. Moreover, sudden unexpected death in epilepsy (SUDEP) is the most important direct epilepsy-related cause of death. Information concerning risk factors for SUDEP is conflicting, but potential risk factors include: age, early onset of epilepsy, duration of epilepsy, uncontrolled seizures, seizure frequency and AED number. Additionally, the cause of SUDEP is still unknown; however, the most commonly suggested mechanisms are cardiac abnormalities during and between seizures. Very recently, our research group was the first to annunciate that winter temperatures may lead a cardiac abnormalities and hence sudden death, become a new potential risk factor to SUDEP. Quite interesting, several mammalian species have evolved to develop a physiological phenomenon called hibernation as a strategy for survival under adverse cold conditions. From cardiovascular point of view, it has been established that hibernating mammals inherited a stable cardiovascular function as a result of adaptation to extreme external and internal environments during hibernation. For instance, hibernating mammals show resistance to hypothermia at a cellular level, the membrane potentials and excitability are more stable in the cardiac cells of these animals (action potentials (60 mV) have been recorded in hibernators myocardium at -5 degrees C), the aortic smooth muscle cells from hibernators are able to maintain ionic gradients upon prolonged exposure to low temperatures, and cardiac myocytes from hibernating mammals maintain constant levels of intracellular free calcium and forceful contractility at 10 degrees C or lower. Taken together, in this paper we postulate that hibernators have some cardiovascular particularities that confer heart protection that could positively influence the cardiovascular system of patients with epilepsy.

OBJECTIVE: To further characterize the capacity of lovastatin to prevent hippocampal neuronal loss after pilocarpine-induced status epilepticus (SE) METHOD: Adult male Wistar rats were divided into four groups: (A) control rats, received neither pilocarpine nor lovastatin (n=5); (B) control rats, received just lovastatin (n=5); (C) rats that received just pilocarpine (n=5); (D) rats that received pilocarpine and lovastatin (n=5). After pilocarpine injection (350mg/kg, i.p.), only rats that displayed continuous, convulsive seizure activity were included in our study. Seizure activity was monitored behaviorally and terminated with an injection of diazepam (10 mg/kg, i.p.) after 4 h of convulsive SE. The rats treated with lovastatin received two doses of 20mg/kg via an oesophagic probe immediately and 24 hours after SE induction. Seven days after pilocarpine-induced SE, all the animals were perfused and their brains were processed for histological analysis through Nissl method. RESULTS: The cell counts in the Nissl-stained sections performed within the hippocampal formation showed a significant cell loss in rats that received pilocarpine and presented SE (CA1= 26.8 ± 13.67; CA3= 38.1 ± 7.2; hilus= 43.8 ± 3.95) when compared with control group animals (Group A: CA1= 53.2 ± 9.63; CA3= 63.5 ± 13.35; hilus= 59.08 ± 10.24; Group B: CA1= 74.3 ± 8.16; CA3= 70.1 ± 3.83; hilus= 70.6 ± 5.10). The average neuronal cell number of CA1 subfield of rats that present SE and received lovastatin (44.4 ± 17.88) was statically significant increased when compared with animals that just presented SE. CONCLUSION: Lovastatin exert a neuroprotective role in the attenuation of brain damage after SE.

Dentre as causas de morte súbita nas epilepsias (SUDEPE), as disfunções cardíacas têm sido uma área de interesse. Sendo assim, o objetivo de nosso estudo foi avaliar a freqüência cardíaca (FC) (in vivo e in vitro) e a pressão ventricular (PV) in vitro de ratos com epilepsia induzida pela pilocarpina. Ratos machos, adultos, da raça Wistar (n=6) receberam pilocarpina para a indução do status epilepticus. Ratos controles (n=6) receberam solução salina ao invés de pilocarpina. Nossos resultados mostram diferenças significantes na freqüência cardíaca in vivo entre os grupos estudados. Em contraste, não encontramos diferenças entre os grupos nos experimentos in vitro. Nossos resultados sugerem que sob a influência do sistema nervoso central, o coração pode apresentar alterações funcionais que aumentam a probabilidade de ocorrência de morte súbita nas epilepsias.

Since cardiovascular dysfunction may contribute to sudden unexpected death in epilepsy (SUDEP), the consumption of omega-3 fatty acids (omega-3 FAs) might be beneficial as an adjunctive therapy for SUDEP prevention. It is well recognized that omega-3 FAs exert positive effects on the cardiovascular system including heart rate (HR) reduction, a major risk factor to sudden death. Thus, we evaluated the effects of chronic supplementation of omega-3 FAs on the HR of rats with epilepsy. In agreement with our previous investigations, this study also showed that the HR of animals with epilepsy is higher than that of the control group. Quite interestingly, chronic supplementation with omega-3 FAs restored the HR of rats with epilepsy toward control values. In conclusion, although further investigations are still required, our preliminary results showed a potential preventive effect of omega-3 FA supplementation against SUDEP.

Studies have demonstrated that median preoptic nucleus (MnPO) neurons play a role in organizing the cardiovascular responses induced by changes in the circulating blood volume. The present study examined whether the MnPO controls cardiovascular function. Male Wistar normotensive (NT) rats and spontaneously hypertensive rats (SHRs; 250-300 g) were anesthetized with urethane (1.2 g kg(-1), i.v.) and instrumented for recordings of mean arterial blood pressure (MAP) and renal blood flow (RBF). The renal vascular conductance (RVC) was calculated as the RBF:MAP ratio and was expressed as a percentage of the baseline value. In the NT rats (n=6), MnPO inhibition produced a MAP reduction (-8.1±1.1 mmHg, p0.05). In the SHRs (n=6), the MAP response to MnPO inhibition was significantly greater (-22.3±4 mmHg, p0.05) than in the NT rats. Furthermore, the increase in the RVC was higher in the SHRs (10.9±3.3%, p0.05). Histological analyses confirmed that the injection sites were confined to the MnPO. We conclude that the MnPO is involved in the tonic regulation of blood pressure in NT rats. Moreover, the greater cardiovascular response to MnPO inhibition observed in the SHRs strongly suggests that the MnPO may contribute to the pathophysiology of essential hypertension.

The aim of the present study was to investigate the coronary effects of Ang-(1–7) [angiotensin-(1–7)] in hypertrophic rat hearts. Heart hypertrophy was induced by abdominal aorta CoA (coarctation). Ang-(1–7) and AVE 0991, a non-peptide Mas-receptor agonist, at picomolar concentration, induced a significant vasodilation in hearts from sham-operated rats. These effects were blocked by the Mas receptor antagonist A-779. Pre-treatment with L-NAME (NG-nitro-L-arginine methyl ester) or ODQ (1H-[1,2,4]oxadiazolo[4,3-a]quinozalin-1-one) [NOS (NO synthase) and soluble guanylate cyclase inhibitors respectively] also abolished the effect of Ang-(1–7) in control hearts. The coronary vasodilation produced by Ang-(1–7) and AVE 0991 was completely blunted in hypertrophic hearts. Chronic oral administration of losartan in CoA rats restored the coronary vasodilation effect of Ang-(1–7). This effect was blocked by A-779 and AT2 receptor (angiotensin II type 2 receptor) antagonist PD123319. Acute pre-incubation with losartan also restored the Ang-(1–7)-induced, but not BK (bradykinin)-induced, coronary vasodilation in hypertrophic hearts. This effect was inhibited by A-779, PD123319 and L-NAME. Chronic treatment with losartan did not change the protein expression of Mas and AT2 receptor and ACE (angiotensin-converting enzyme) and ACE2 in coronary arteries from CoA rats, but induced a slight increase in AT2 receptor in aorta of these animals. Ang-(1–7)-induced relaxation in aortas from sham-operated rats was absent in aortas from CoA rats. In vitro pre-treatment with losartan restored the Ang-(1–7)-induced relaxation in aortic rings of CoA rats, which was blocked by the Mas antagonist A-779 and L-NAME. These data demonstrate that Mas is strongly involved in coronary vasodilation and that AT1 receptor (angiotensin II type 1 receptor) blockade potentiates the vasodilatory effects of Ang-(1–7) in the coronary beds of pressure-overloaded rat hearts through NO-related AT2- and Mas-receptor-dependent mechanisms. These data suggest the association of Ang-(1–7) and AT1 receptor antagonists as a potential therapeutic avenue for coronary artery diseases.

Entre as causas de morte súbita em epilepsia (SUDEPE), os efeitos das drogas antiepilépticas no coração têm sido pobremente explorados. Desta forma, o objetivo deste estudo foi avaliar a frequência cardíaca (in vivo e de forma isolada ex vivo) e a pressão ventricular (de forma isolada ex vivo) de ratos com e sem epilepsia tratados com carbamazepina. Quatro grupos de ratos Wistar machos adultos (peso 200 a 250 g) foram estudados: [A] ratos controle (n=8), não receberam pilocarpina ou carbamazepina; [B] ratos tratados com carbamazepina (n=8), receberam dose diária de carbamazepina de 120 mg/kg intraperitoneal, durante duas semanas (n=8); [C] ratos com epilepsia que receberam solução salina; [D] ratos com epilepsia que receberam dose diária de carbamazepina de 120 mg/kg intraperitoneal durante duas semanas. Nossos resultados evidenciaram uma diferença estatisticamente significativa na média da freqüência cardíaca in vivo entre os animais com epilepsia (com e sem o uso de carbamazepina) quando comparados aos grupos controles in vivo. Em contraste, não observamos diferenças estatísticas nos experimentos ex vivo quando comparados os animais com ou sem epilepsia, a despeito do uso da carbamazepina. Nossos resultados sugerem que, de forma isolada, a carbamazepina pode não ser um fator de risco potencial para a ocorrência de morte súbita em epilepsia. Among the causes for sudden unexpected death (SUDEP) in epilepsy, the effects of antiepileptic drugs on the heart have been poorly explored. Based on this, the aim of our study was to evaluate the heart rate (in vivo and isolated ex vivo) and ventricular pressure (isolated ex vivo) of rats with and without epilepsy treated with carbamazepine. Four groups of adult, male Wistar rats (200-250 g) were studied: [A] control rats (n=8), received neither pilocarpine nor carbamazepine [B] carbamazepine-treated rats (n=8), received a daily dose of 120 mg/Kg, i.p. of carbamazepine for two weeks; [C] rats with epilepsy that received just saline solution (n=8); [D] rats with epilepsy that received a daily dose of 120 mg/Kg, i.p. of carbamazepine for two weeks (n=8). Our results showed significant increase in heart rate in animals with epilepsy (with and without the use of carbamazepine) when compared to the control groups in vivo. In contrast, we did not find differences during isolated ex vivo experiments comparing animals with and without epilepsy and despite the use of carbamazepine. Our results suggest that, in isolation, carbamazepine may not be a potential risk factor for sudden unexpected death in epilepsy. Federal University of São Paulo Paulist Medicine School UNIFESP-EPM Physiology Department Presbiterian Mackenzie University Center of Biological Sciences and Health Program Graduate Development Disorders University of São Paulo Ribeirão Preto Medicine School Department of Neurosciences and Behavior Sciences UNIFESP, Paulist Medicine School UNIFESP, EPM Physiology Department SciELO

Submitted by Guilherme Lemeszenski (guilherme@nead.unesp.br) on 2013-08-22T18:41:42Z No. of bitstreams: 1 S1517-86922008000600007.pdf: 88055 bytes, checksum: c4e0db51270e5be79fd726fdaf20c60f (MD5) Made available in DSpace on 2013-08-22T18:41:42Z (GMT). No. of bitstreams: 1 S1517-86922008000600007.pdf: 88055 bytes, checksum: c4e0db51270e5be79fd726fdaf20c60f (MD5) Previous issue date: 2008-12-01 Made available in DSpace on 2013-09-30T19:28:28Z (GMT). No. of bitstreams: 2 S1517-86922008000600007.pdf: 88055 bytes, checksum: c4e0db51270e5be79fd726fdaf20c60f (MD5) S1517-86922008000600007.pdf.txt: 31275 bytes, checksum: 70540dd6e017f5d88928a0c80b656714 (MD5) Previous issue date: 2008-12-01 Submitted by Vitor Silverio Rodrigues (vitorsrodrigues@reitoria.unesp.br) on 2014-05-20T13:22:59Z No. of bitstreams: 2 S1517-86922008000600007.pdf: 88055 bytes, checksum: c4e0db51270e5be79fd726fdaf20c60f (MD5) S1517-86922008000600007.pdf.txt: 31275 bytes, checksum: 70540dd6e017f5d88928a0c80b656714 (MD5) Made available in DSpace on 2014-05-20T13:22:59Z (GMT). No. of bitstreams: 2 S1517-86922008000600007.pdf: 88055 bytes, checksum: c4e0db51270e5be79fd726fdaf20c60f (MD5) S1517-86922008000600007.pdf.txt: 31275 bytes, checksum: 70540dd6e017f5d88928a0c80b656714 (MD5) Previous issue date: 2008-12-01 Embora a análise no domínio da freqüência do sinal eletromiográfico (EMG) seja empregada na caracterização do processo de fadiga muscular localizada, sua aplicação, especificamente a da freqüência mediana (Fmed), é pouco explorada no âmbito esportivo. O objetivo do presente estudo foi verificar a viabilidade da aplicação do sinal EMG, através de sua análise no domínio da freqüência, como parâmetro para determinação e diferenciação no comportamento da fadiga muscular localizada. Dois grupos de sujeitos, um caracterizado como atletas (n =12) e outro como sedentários (n =12), foram submetidos a análises baseadas em procedimentos executados em três diferentes situações experimentais, todos envolvendo a modalidade de exercício isométrico: i) teste máximo para determinação da contração isométrica voluntária máxima (CIVM); ii) teste de fadiga, sustentado por 35 seg. a 80% da CIVM; iii) teste de recuperação, sustentado por 10 seg. a 80% da CIVM; neste ultimo foi monitorado o comportamento da Fmed nos três primeiros (Fmedi) e três últimos segundos (Fmedf) do sinal EMG no músculo tibial anterior durante o teste de fadiga. Durante os 10 segundos do teste de recuperação foi calculada a Fmed referente a todo o período (Fmedr). parâmetro utilizado no cálculo do índice de recuperação muscular (IRM). Os resultados apontam que a Fmedf apresentou valor menor em relação à Fmedi em ambos os grupos (p < 0,05). Quando comparado com o grupo de sedentários, o grupo de atletas apresentou valores maiores de Fmedi e Fmedf (p < 0,05). O valor médio e desvio-padrão do IRM para o grupo de atletas foram de 62,1% ± 28,7 e, para o grupo de sedentários, de 55,2% ± 27,8 (p > 0,05). Dessa forma, os resultados apresentados neste estudo permitem inferir a viabilidade na aplicação de parâmetros no domínio da freqüência do sinal EMG para a determinação e diferenciação do comportamento da fadiga muscular localizada. Although the analysis in the frequency domain of the Electromyographic Signal (EMG) has been used in the characterization of the localized muscular fatigue process, its application, specifically the Median Frequency (MF), is rarely explored in sports. The objective of this study was to verify the viability of the EMG signal application, through its frequency domain analysis, as a parameter for determination and differentiation of the behavior of localized muscle fatigue. Two groups of subjects, one characterized as athletes (n = 12) and the other as sedentary (n = 12), were submitted to analysis based on procedures from three different experimental situations, all involving isometric exercise modality: i) maximum test for determination of the Maximum Voluntary Isometric Contraction (MVIC); ii) fatigue test, 35 sec. sustained load of 80% of MVIC; iii) recovery test, 10 sec. sustained load of 80% of MVIC. In the latter, the MF behavior in the three first (Fmedi) and three last (Fmedf) seconds of the EMG signal of tibialis anterior muscle during the fatigue test have been monitored. During the 10 seconds of the recovery test, MF was calculated regarding the whole period (Fmedr); this parameter was used to calculate the Muscular Recovery Index (MRI). The results showed that Fmedf presented lower value in relation to Fmedi in both groups (p < 0.05). Additionally, the Fmedi and Fmedf values for the athlete group were higher in comparison to the sedentary group (p < 0.05). The MRI mean value and standard deviation for the athlete group were 62.1% ± 28.7 and for the sedentary group was 55.2% ± 27.8 (p > 0.05). Therefore, the results presented in this study allow inferring the viability in the application of the frequency domain parameters of the EMG signal for the determination and differentiation of localized muscle fatigue behavior. Unifesp Escola Paulista de Medicina Programa de Pós-Graduação em Fisiologia do Exercício Universidade do Oeste Paulista (UNOESTE) Faculdade de Fisioterapia Unesp Laboratório de Fisioterapia Aplicada ao Movimento Humano Instituto de Ensino e Pesquisa Movimentare® Fisioterapia e Reabilitação Unifesp Escola Paulista de Medicina Unesp Laboratório de Fisioterapia Aplicada ao Movimento Humano

Sudden unexpected death in epilepsy (SUDEP) is the commonest cause of seizure-related mortality in people with refractory epilepsy. Several risk factors for SUDEP are described; however, the importance of including low temperatures as risk factor for SUDEP was never explored. Based on this, the aim of this study was to evaluate the heart rate of rats with epilepsy during low temperature exposure. Our results showed that low temperature clearly increased the heart rate of rats with epilepsy. Taken together, we concluded that exposure to low temperatures could be considered important risk factors from cardiovascular abnormalities and hence sudden cardiac death in epilepsy.

Epilepsy is the most common neurological disorder, approximately 1% of the population worldwide have epilepsy. Moreover, sudden unexpected death in epilepsy (SUDEP) is the most important direct epilepsy-related cause of death. Information concerning risk factors for SUDEP is conflicting, but potential risk factors include: age, early onset of epilepsy, duration of epilepsy, uncontrolled seizures, seizure frequency, AED number and winter temperatures. Additionally, the cause of SUDEP is still unknown; however, the most commonly suggested mechanisms are cardiac abnormalities during and between seizures. Furthermore, the evidence from the last 10 years suggests that melatonin has an important role in the epileptogenesis process and influences the cardiovascular system as well. The positive effect of melatonin has been demonstrated against different convulsive stimuli in several rodents, including seizures induced by pentylenetetrazole kainate, glutamate, maximal electrical shock and electrically kindled stimulation of amygdala. Clinical studies have also demonstrated a positive role of melatonin on the seizure frequency in children and reduced spiking activity and seizure frequency in patients with intractable epilepsy. In the rat hearts, studies in vivo and in vitro using pharmacological concentrations of melatonin confirmed an anti-arrhythmic effect of this hormone and studies in humans have been shown that chronic heart disease patients have significantly lower melatonin levels in their blood stream than do normal individuals. Thus, caution should be taken in generalization of these findings to epileptic population. Moreover, it is important to note that when dealing with intractable epilepsy that do not respond to any conventional treatment, the additional of melatonin may be evaluated. Taken together, in this paper we suggested a possible relationship between cardiac abnormalities, melatonin and SUDEP.

OBJETIVOS: A morte súbita em epilepsia (SUDEP) é a principal causa de morte entre os pacientes com epilepsia. Alterações morfológicas e funcionais do coração estão relacionadas com a SUDEP. Nesse sentido, o objetivo deste estudo foi avaliar a concentração de troponina I, um importante marcador de lesão do miocárdio, em pacientes com epilepsia do lobo temporal de difícil controle e que foram submetidos à ressecção cirúrgica e que não obtiveram sucesso com esta abordagem terapêutica. METODOLOGIA: Onze pacientes participaram do estudo e todos continuaram a apresentar crises após o tratamento cirúrgico. Os valores de troponina I indicativos de lesão seriam aqueles maiores de 1 ng/ml e o valor mínimo detectável pelo kit utilizado em nosso estudo foi de 0,15 ng/ml. RESULTADOS: Apenas três pacientes apresentaram níveis de troponina I detectáveis. Em relação aos níveis detectáveis de troponina I, não encontramos nenhuma relação com sexo, idade e lateralidade da lesão. CONCLUSÕES: APESAr de não termos encontrado resultados positivos em nosso estudo, o papel do coração na SUDEP não pode ser descartado, já que algumas lesões, embora não sendo capazes de alterar os níveis séricos de troponina I, podem ser suficientes na gênese de focos arritmogênicos. PURPOSE: Sudden unexpected death in epilepsy (SUDEP) is the main cause of death in patients with epilepsy. Morphologic and functional changes in the heart are related to SUDEP. The aim of our study was to verify the concentration of troponin I, an important marker of myocardium damage, in patients with temporal lobe epilepsy who were submitted to surgical resection and were not seizure-free after the procedure. METHODS: Eleven non-consecutive patients participated in the study and all of them presented poor seizure control after surgical procedure. Troponin I levels higher then 1 ng/ml indicate myocardium damage. The detection level of the kit used in our study was 0,15 ng/ml. RESULTS: Only three patients showed detectable troponin I levels. The troponin I levels found in our study is not related with sex, age or side of the lesion. CONCLUSIONS: In spite of we did not find positive results in our study, an active role of the heart in SUDEP cannot be discarded, since some injuries, even so not being capable to modify troponin I levels, can be enough to generate arrhythmogenic foci.

Studies has showed beneficial effects of physical exercise in epilepsy. Thus, sudden death in epileptic patients is higher than in no epileptic. It is well known the positive effects of exercise to the prevention and rehabilitation of cardiac diseases. Based on this, we analyzed the heart rate in vivo and in vitro and the ventricular pressure in vitro of rats with epilepsy submitted to an aerobic physical exercise program. Adult male Wistar rats were divided into 4 groups of 6 animals: epilepsy group, trained epilepsy group, control group, trained control group. The pilocarpine model was used to obtain epilepsy groups. Trained groups were submitted to aerobic exercise program consisting of 30 days during 50 min at 60% of VO2 max. Our results showed difference in heart rate in vivo only in animals with epilepsy when compared with control animals. A significant difference in heart rate in vitro was observed in trained animals with epilepsy when compared with animals with epilepsy. No significant difference in the ventricular pressure in vitro was observed among all groups. These results suggest an altered intrinsic autorhythmicity of trained animals with epilepsy, however, without altered heart contractility function.

Among the causes for sudden death in epilepsy, cardiac dysfunction has been an area of interest. Based on this, the aim of our study was to evaluate the heart rate (in vivo and in vitro) and ventricular pressure in vitro of rats with epilepsy induced by pilocarpine. Adult male Wistar rats (n=6) were given pilocarpine hydrochloride to induce status epilepticus. Control rats (n=6) received saline solution instead pilocarpine. Our results showed significant differences in the mean of heart rate in vivo between the groups. In contrast, we did not find differences during in vitro experiments. Our results suggest a central nervous system modulation on the heart, which could explain the sudden unexpected death in epilepsy.

Hypernatremia stimulates the secretion of oxytocin (OT), but the physiological role of OT remains unclear. The present study sought to determine the involvement of OT and renal nerves in the renal responses to an intravenous infusion of hypertonic saline. Male Wistar rats (280-350 g) were anesthetized with sodium thiopental (40 mg. kg(-1), i.v.). A bladder cannula was implanted for collection of urine. Animals were also instrumented for measurement of mean arterial pressure (MAP) and renal blood flow (RBF). Renal vascular conductance (RVC) was calculated as the ratio of RBF by MAP. In anesthetized rats (n = 6), OT infusion (0.03 µg • kg(-1), i.v.) induced renal vasodilation. Consistent with this result, ex vivo experiments demonstrated that OT caused renal artery relaxation. Blockade of OT receptors (OXTR) reduced these responses to OT, indicating a direct effect of this peptide on OXTR on this artery. Hypertonic saline (3 M NaCl, 1.8 ml • kg(-1) b.wt., i.v.) was infused over 60 s. In sham rats (n = 6), hypertonic saline induced renal vasodilation. The OXTR antagonist (AT; atosiban, 40 µg • kg(-1) • h(-1), i.v.; n = 7) and renal denervation (RX) reduced the renal vasodilation induced by hypernatremia. The combination of atosiban and renal denervation (RX+AT; n = 7) completely abolished the renal vasodilation induced by sodium overload. Intact rats excreted 51% of the injected sodium within 90 min. Natriuresis was slightly blunted by atosiban and renal denervation (42% and 39% of load, respectively), whereas atosiban with renal denervation reduced sodium excretion to 16% of the load. These results suggest that OT and renal nerves are involved in renal vasodilation and natriuresis induced by acute plasma hypernatremia.

Allancer DC Nunes,1 Laylla S Ramalho,2Álvaro PS Souza,1Elizabeth P Mendes,1,3Diego B Colugnati,1Nícholas Zufelato,2Marcelo H Sousa,4Andris F Bakuzis,2Carlos H Castro1,3 1Department of PhysiologicalSciences, 2Physics Institute, Federal University of Goiás, Goiânia, Brazil;3National Institute of Science andTechnology in Nanobiopharmaceutics,Belo Horizonte, Brazil; 4Faculty of Ceilândia, University of Brasília, Brasília-DF, Brazil Abstract: Magnetic nanoparticles (MNPs) have been used for various biomedical applications. Importantly, manganese ferrite-based nanoparticles have useful magnetic resonance imaging characteristics and potential for hyperthermia treatment, but their effects in the cardiovascular system are poorly reported. Thus, the objectives of this study were to determine the cardiovascular effects of three different types of manganese ferrite-based magnetic nanoparticles: citrate-coated (CiMNPs); tripolyphosphate-coated (PhMNPs); and bare magnetic nanoparticles (BaMNPs). The samples were characterized by vibrating sample magnetometer, X-ray diffraction, dynamic light scattering, and transmission electron microscopy. The direct effects of the MNPs on cardiac contractility were evaluated in isolated perfused rat hearts. The CiMNPs, but not PhMNPs and BaMNPs, induced a transient decrease in the left ventricular end-systolic pressure. The PhMNPs and BaMNPs, but not CiMNPs, induced an increase in left ventricular end-diastolic pressure, which resulted in a decrease in a left ventricular end developed pressure. Indeed, PhMNPs and BaMNPs also caused a decrease in the maximal rate of left ventricular pressure rise (+dP/dt) and maximal rate of left ventricular pressure decline (–dP/dt). The three MNPs studied induced an increase in the perfusion pressure of isolated hearts. BaMNPs, but not PhMNPs or CiMNPs, induced a slight vasorelaxant effect in the isolated aortic rings. None of the MNPs were able to change heart rate or arterial blood pressure in conscious rats. In summary, although the MNPs were able to induce effects ex vivo, no significant changes were observed in vivo. Thus, given the proper dosages, these MNPs should be considered for possible therapeutic applications. Keywords: cardiac function, isolated heart, magnetic fluids, magnetic nanoparticles, nanomedicine

Submitted by Vitor Silverio Rodrigues (vitorsrodrigues@reitoria.unesp.br) on 2014-05-27T11:30:41Z No. of bitstreams: 0Bitstream added on 2014-05-27T14:32:57Z : No. of bitstreams: 1 2-s2.0-84883826525.pdf: 1527930 bytes, checksum: b3c6a8f9413d8aaa0a45380cd9b6e29c (MD5) Made available in DSpace on 2014-05-27T11:30:41Z (GMT). No. of bitstreams: 0 Previous issue date: 2013-09-10 Noradrenergic neurons in the caudal ventrolateral medulla (CVLM; A1 group) contribute to cardiovascular regulation. The present study assessed whether specific lesions in the A1 group altered the cardiovascular responses that were evoked by hypertonic saline (HS) infusion in non-anesthetized rats. Male Wistar rats (280-340 g) received nanoinjections of antidopamine-β-hydroxylase-saporin (A1 lesion, 0.105 ng.nL-1) or free saporin (sham, 0.021 ng.nL-1) into their CVLMs. Two weeks later, the rats were anesthetized (2% halothane in O2) and their femoral artery and vein were catheterized and led to exit subcutaneously between the scapulae. On the following day, the animals were submitted to HS infusion (3 M NaCl, 1.8 ml • kg-1, b.wt., for longer than 1 min). In the sham-group (n = 8), HS induced a sustained pressor response (ΔMAP: 35±3.6 and 11±1.8 mmHg, for 10 and 90 min after HS infusion, respectively; P

It is thought that cardiovascular changes may contribute to sudden death in patients with epilepsy. To examine cardiovascular alterations that occur during epileptogenesis, we measured the heart rate of rats submitted to the electrical amygdala kindling model. Heart rate was recorded before, during, and after the induced seizures. Resting heart rate was increased in stages 1, 3, and 5 as compared with the unstimulated control condition. In the initial one third of the seizures, we observed bradycardia, which increased in intensity with increasing stage and was blocked by injecting methyl atropine. During stage 5 seizures, a rebound tachycardia was observed that also increased in intensity with increasing number of seizures. This study demonstrated the influence of seizure frequency on cardiac autonomic modulation, providing a basis for discussion of potential mechanisms that cause patients with epilepsy to die suddenly.