Abstract Aims Although reduced life expectancy in Parkinson's Disease (PD) patients has been related to severe cardiac arrhythmias due to autonomic dysfunctions, its molecular mechanisms remain unclear. To investigate the role of cardiac β1-Adrenergic (β1AR) and A1-Adenosine (A1R) receptors in these dysfunctions, the pharmacological effects of stimulation of cardiac β1AR (isoproterenol, ISO), in the absence and presence of cardiac β1AR (atenolol, AT) or A1R (1,3-dipropyl-8-cyclopentyl xanthine, DPCPX) blockade, on the arrhythmias induced by Ischemia/Reperfusion (CIR) in an animal PD model were studied. Methods PD was produced by dopaminergic lesions (confirmed by immunohistochemistry analysis) caused by the injection of 6-hydroxydopamine (6-OHDA, 6 μg) in rat striatum. CIR was produced by a surgical interruption for 10 min followed by reestablishment of blood circulation in the descendent left coronary artery. On the incidence of CIR-Induced Ventricular Arrhythmias (VA), Atrioventricular Block (AVB), and Lethality (LET), evaluated by Electrocardiogram (ECG) analysis, the effects of intravenous treatment with ISO, AT and DPCPX (before CIR) were studied. Results VA, AVB and LET incidences were significantly higher in 6-OHDA (83%, 92%, 100%, respectively) than in control rats (58%, 67% and 67%, respectively). ISO treatment significantly reduced these incidences in 6-OHDA (33%, 33% and 42%, respectively) and control rats (25%, 25%, 33%, respectively), indicating that stimulation of cardiac β1AR induced cardioprotection. This response was prevented by pretreatment with AT and DPCPX, confirming the involvement of cardiac β1AR and A1R. Conclusion Pharmacological modulation of cardiac β1AR and A1R could be a potential therapeutic strategy to reduce severe arrhythmias and increase life expectancy in PD patients. Parkinsons Parkinson s (PD dysfunctions unclear β1Adrenergic βAdrenergic β1 Adrenergic β βAR AR (β1AR A1Adenosine AAdenosine A1 Adenosine A R (A1R isoproterenol, isoproterenol (isoproterenol , ISO) atenolol, atenolol (atenolol 1,3dipropyl8cyclopentyl 13dipropyl8cyclopentyl dipropylcyclopentyl 1,3 dipropyl 8 cyclopentyl 1 3 xanthine blockade IschemiaReperfusion Ischemia Reperfusion (CIR studied confirmed analysis 6hydroxydopamine hydroxydopamine 6OHDA, 6OHDA OHDA OHDA, (6-OHDA μg striatum artery CIRInduced Induced VA (VA) AVB, (AVB) LET, (LET) ECG (ECG before 83%, 83 (83% 92 92% 100 100% respectively 58%, 58 (58% 67 respectively. . 33 (33% 42 42% 25 (25% 25% respectively, cardioprotection 3dipropyl8cyclopentyl 13 1, (VA (AVB (LET 83% (83 9 58% 5 (58 (33 4 2 (25 (8 (5 (3 (2 (

OBJECTIVES: In addition to the classic motor symptoms of Parkinson’s disease (PD), patients also present with non-motor symptoms, such as autonomic dysfunction, which is present in almost 90% of patients with PD, affecting the quality of life and mortality. Regarding sex differences in prevalence and presentation, there is increasing concern about how sex affects autonomic dysfunction. However, there are no previous data on autonomic cardiac function in females after 6-hydroxydopamine (6-OHDA) striatal injection. METHODS: Wistar female rats were ovariectomized. After 20 days, the animals received bilateral injections of 6-OHDA (total dose per animal: 48 µg) or a vehicle solution in the striatum. Thirty days after 6-OHDA injection, subcutaneous electrodes were implanted for electrocardiogram (ECG) recording. Ten days after electrode implantation, ECG signals were recorded. Analyses of heart rate variability (HRV) parameters were performed, and the 6-OHDA lesion was confirmed by analyzing the number of tyrosine hydroxylase-positive neurons in the substantia nigra pars compacta (SNpc). RESULTS: A high dose of 6-OHDA did not affect HRV of females, independent of ovariectomy. As expected, ovariectomy did not affect HRV or lesions in the SNpc after 6-OHDA injection. CONCLUSIONS: We suggest that females with 6-OHDA present with cardioprotection, independent of ovarian hormones, which could be related to female vagal predominance.

ABSTRACT Purpose To evaluate the preventive cardioprotective effects of resveratrol and grape products, such as grape juice and red wine, in animal model of cardiac ischemia and reperfusion. Methods Male Wistar rats orally pretreated for 21-days with resveratrol and grape products were anesthetized and placed on mechanical ventilation to surgically induce cardiac ischemia and reperfusion by obstruction (ischemia) followed by liberation (reperfusion) of blood circulation in left descending coronary artery. These rats were submitted to the electrocardiogram (ECG) analysis to evaluate the effects of pretreatment with resveratrol and grape products on the incidence of ventricular arrhythmias (VA), atrioventricular block (AVB) and lethality (LET) resulting from cardiac ischemia and reperfusion. Results It was observed that the incidence of AVB was significantly lower in rats pretreated with resveratrol (25%), grape juice (37.5%) or red wine (12.5%) than in rats treated with saline solution (80%) or ethanol (80%). Similarly, incidence of LET was also significantly lower in rats pretreated with resveratrol (25%), grape juice (25%) or red wine (0%) than in rats treated with saline solution (62.5%) or ethanol (75%). Conclusions These results indicate that the cardioprotective response stimulated by resveratrol and grape products prevents the lethal cardiac arrhythmias in animal model of ischemia and reperfusion, supporting the idea that this treatment can be beneficial for prevention of severe cardiac arrhythmias in patients with ischemic heart disease.

Abstract Purpose To evaluate whether the attenuation of mitochondrial Ca2+ overload produced by pharmacological blockade of mitochondrial Ca2+ uniporter (MCU) protects the myocardium against injuries caused by cardiac ischemia and reperfusion (CIR). Methods CIR was induced in adult male Wistar rats (300-350 g) by occlusion of the left anterior descendent coronary artery (10 min), followed by reperfusion (120 min). Rats were treated with different doses of MCU blocker ruthenium red (RuR), administered 5 min before ischemia or reperfusion. Results In untreated rats, the incidences of ventricular arrhythmias (VA), atrioventricular block (AVB) and the lethality (LET) induced by CIR were 85%, 79% and 70%, respectively. In rats treated with RuR before ischemia, the incidences of VA, AVB and LET were significantly reduced to 62%, 25% and 25%, respectively. In rats treated with RuR after ischemia, the incidences of VA, AVB and LET were significantly reduced to 50%, 25% and 25%, respectively. Conclusion The significant reduction of the incidence of CIR-induced VA, AVB and LET produced by the treatment with RuR indicates that the attenuation of mitochondrial Ca2+ overload produced by pharmacological blockade of MCU can protect the myocardium against injuries caused by CIR.

Abstract Purpose: To evaluate the cardioprotective response of the pharmacological modulation of β-adrenergic receptors (β-AR) in animal model of cardiac ischemia and reperfusion (CIR), in spontaneously hypertensive (SHR) and normotensive (NWR) rats. Methods: CIR was induced by the occlusion of left anterior descendent coronary artery (10 min) and reperfusion (75 min). The SHR was treated with β-AR antagonist atenolol (AT, 10 mg/kg, IV) 5 min before CIR, and NWR were treated with β-AR agonist isoproterenol (ISO, 0.5 mg/kg, IV) 5 min before CIR. Results: The treatment with AT increased the incidence of VA, AVB and LET in SHR, suggesting that spontaneous cardioprotection in hypertensive animals was abolished by blockade of β-AR. In contrast, the treatment with ISO significantly reduced the incidence of ventricular arrhythmia, atrioventricular blockade and lethality in NWR (30%, 20% and 20%, respectively), suggesting that the activation of β-AR stimulate cardioprotection in normotensive animals. Serum CK-MB were higher in SHR/CIR and NWR/CIR compared to respective SHAM group (not altered by treatment with AT or ISO). Conclusion: The pharmacological modulation of β-AR could be a new cardioprotective strategy for the therapy of myocardial dysfunctions induced by CIR related to cardiac surgery and cardiovascular diseases.

A epilepsia é o distúrbio neurológico crônico mais comum no mundo. O tratamento farmacológico é essencial na maioria dos casos. Entretanto, terapias não farmacológicas, como a prática de atividade física regular, vêm sendo estudadas para o tratamento complementar desse distúrbio. Já está bem estabelecido que programas de atividade física promovem benefícios sobre a aptidão física e a saúde. Contudo, pessoas com epilepsia frequentemente são desencorajadas a participar desses programas. Essa relutância origina-se da proteção excessiva dos profissionais da saúde e familiares, pois existe o receio que a prática de atividade física possa predispor os indivíduos a lesões traumáticas ou que a fadiga resultante do esforço físico possa precipitar uma nova crise epiléptica. Evidências crescentes mostram que a prática de atividade física é benéfica para pessoas com epilepsia, havendo poucos achados mostrando o aumento da frequência de crises ou do risco de lesão quando a doença está farmacologicamente controlada. Portanto, o objetivo da presente revisão é apresentar os possíveis riscos e benefícios da prática de atividade física por pessoas com epilepsia.

Epilepsy is the most common chronic neurological disorder in the world. Pharmacological treatment is essential in the majority of cases. However, nonpharmacologic therapies such as regular physical activity have been studied in the treatment of epilepsy. It was well established that the regular physical activity provides benefits on physical fitness and health. However, people with epilepsy are often discouraged from participating in physical activity programs. This reluctance derived from overprotection of health's professionals and relatives, because there are fears that the practice of physical activity may predispose individuals to traumatic injury or that fatigue resulting from physical effort can precipitate a seizure. Growing evidence shows that regular physical activity is beneficial for individuals with epilepsy, with few findings showing an increase in seizure frequency or risk of injury when the disease is pharmacologically controlled. Therefore, the purpose of this review is to present the possible risks and benefits of regular physical activity for people with epilepsy.

Pessoas com epilepsia apresentam baixa participação em atividades físicas. Um importante problema nos cuidados da epilepsia é a falta de profissionais qualificados. Neste estudo apresentamos dados de uma pesquisa para avaliar o conhecimento de professores de educação física sobre a epilepsia. Um questionário foi respondido por 134 educadores físicos de ambos os sexos. Sessenta por cento dos profissionais acreditam que a crise epilética é uma descarga elétrica anormal do cérebro, 13% que a epilepsia é uma doença crônica cerebral que não pode ser curada ou controlada, 84% que pessoas que têm convulsões não necessariamente apresentam epilepsia e 5% que pessoas com epilepsia têm dificuldade de aprendizado. Em relação à experiência prévia do profissional, 61% presenciaram uma crise epilética e 53% tiveram acesso a alguma informação sobre epilepsia. Além disso, 28% dos profissionais possuíam amigo ou parente com epilepsia, 14% tinham um aluno com epilepsia e 29% já tinham socorrido alguém durante uma crise. Nossos achados revelam uma falta de conhecimento apropriado dos profissionais da área de educação física sobre a epilepsia. A melhora desse conhecimento pode contribuir para um adequado tratamento e cuidado da pessoa com epilepsia.

People with epilepsy suffer from a considerable lack of physical activity. In addition, an important problem of epilepsy management is the lack of qualified professionals. In this study we present data from a survey which aimed to assess physical educators' general knowledge about epilepsy. One hundred and thirty four physical educators of both sexes answered a questionnaire. Sixty percent of the professionals believe that a seizure is an abnormal electrical discharge of the brain, 13% that epilepsy is a cerebral chronic disease that can not be cured or controlled, 84% that people having convulsions will not necessarily present epilepsy and 5% that people with epilepsy have difficulties of learning. Questions concerned previous professional experience with epilepsy showed that 61% have seen a seizure and 53% have access to some information about epilepsy. Thus, 28% of professionals have a friend or relative with epilepsy, 14% have a student with epilepsy, and 29% helped someone during seizures. Our findings reveal a lack of physical educators' appropriate knowledge about epilepsy. Improvement of this might contribute to the improvement of epilepsy care/management.

Pessoas com epilepsia têm sido desencorajadas a participar de atividades físicas por medo que o exercício físico possa exacerbar as crises epilépticas. Apesar dos efeitos benéficos do exercício físico aeróbico em pessoas com epilepsia, informações em relação à intensidade do exercício têm sido pouco estudadas. Neste estudo, investigamos o efeito do exercício físico incremental até a exaustão (teste ergométrico) em pessoas com epilepsia. Dezessete pessoas com epilepsia do lobo temporal e vinte e um indivíduos saudáveis (controles) participaram do estudo. Os dois grupos foram submetidos a ecocardiograma e eletrocardiograma em repouso e durante o esforço físico. Nenhum indivíduo com epilepsia apresentou crises durante o esforço físico ou no período de recuperação do teste ergométrico. Ambos os grupos apresentaram respostas fisiológicas da frequência cardíaca e pressão arterial durante os diferentes estágios do teste de esforço. Somente algumas pessoas com epilepsia apresentaram alterações ecocardiográficas e eletrocardiográficas em repouso ou durante o esforço. Em conclusão, este estudo sugere que o esforço físico exaustivo parece não ser um componente indutor de crises epilépticas.

People with epilepsy have been discouraged from participating in physical activity due to the fear that it will exacerbate seizures. Although the beneficial effect of aerobic exercise in people with epilepsy, little objective evidence regarding the intensity of exercise has been reported. We investigated the effect of incremental physical exercise to exhaustion in people with epilepsy. Seventeen persons with temporal lobe epilepsy and twenty one control healthy subjects participated in this study. Both groups were submitted to echocolordoppler and electrocardiogram at rest and during physical effort. None of patients reported seizures during physical effort or in the recovery period of ergometric test. Both groups presented physiological heart rate and blood pressure responses during the different stages of the ergometric test. Only few patients presented electrocardiography or echocardiography alterations at rest or during effort. In conclusion, this work suggests that physical effort to exhaustion is not a seizure-induced component.