Reduction of vascular reactivity in rat aortas following pilocarpine-induced status epilepticus

Abstract Objective: The authors investigated changes in vascular reactivity in rats following pilocarpine-induced status epilepticus. Method: Male Wistar rats weighing between 250g and 300g were used. Status epilepticus was induced using 385 mg/kg i.p. pilocarpine. After 40 days the thoracic aorta was dissected and divided into 4 mm rings and the vascular smooth muscle reactivity to phenylephrine was evaluated. Results: Epilepsy decreased the contractile responses of the aortic rings to phenylephrine (0.1 nM-300 mM). To investigate if this reduction was induced by increasing NO production with/or hydrogen peroxide L-NAME and Catalase were used. L-NAME (N-nitro-L arginine methyl ester) increased vascular reactivity but the contractile response to phenylephrine increased in the epileptic group. Catalase administration decreased the contractile responses only in the rings of rats with epilepsy. Conclusions: Our findings demonstrated for the first time that epilepsy is capable of causing a reduction of vascular reactivity in rat aortas. These results suggest that vascular reactivity reduction is associated with increased production of Nitric Oxide (NO) as an organic attempt to avoid hypertension produced by excessive sympathetic activation.

Role of cardiac β1-adrenergic and A1-adenosine receptors in severe arrhythmias related to Parkinson's disease

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.

Ischemic stroke in 455 COVID-19 patients

ABSTRACT There is increasing evidence that COVID-19 can be associated with ischemic stroke (COVID-stroke). The frequency and pathogenesis of COVID-stroke, however, remains largely unknown. This narrative review aimed at summarizing and discussing current knowledge about frequency and pathogenesis of COVID-stroke in 455 patients collected from the literature. COVID-stroke occurs in all age groups and predominantly in males. The anterior circulation is more frequently affected than the posterior circulation. COVID-stroke is most frequently embolic. The severity of COVID-stroke ranges from NIHSS 3 to 32. Cardiovascular risk factors are highly prevalent in patients with COVID-stroke. COVID-stroke occurs simultaneously with the onset of pulmonary manifestations or up to 40 days later. Clinical manifestations of COVID-19 are most frequently mild or even absent. The majority of patients with COVID-stroke achieve complete or partial recovery, but in one-quarter of patients, the outcome is fatal. In conclusion, the frequency of ischemic stroke has not increased since the outbreak of the SARS-CoV-2 pandemic. COVID-stroke predominantly affects males and the anterior circulation. COVID-stroke is multifactorial but predominantly embolic and more frequently attributable to cardiovascular risk factors than to coagulopathy.

Peripheral neuropathy in COVID-19 is due to immune-mechanisms, pre-existing risk factors, anti-viral drugs, or bedding in the Intensive Care Unit / Neuropatia periférica na COVID-19 com mecanismos immunológicos, fatores de risco preexistentes, medicamentos antivirais e compressão dos nervos periféricos nos leitos da Unidade de Terapia Intensiva

ABSTRACT Background: This mini-review aims to summarize and discuss previous and recent advances in the clinical presentation, pathophysiology, diagnosis, treatment, and outcome of SARS-CoV-2-associated peripheral neuropathies. Methods: Literature review. Results: Altogether, 105 articles about SARS-CoV-2-associated neuropathy describing 261 patients were retrieved. Peripheral neuropathy in patients with COVID-19 is frequent and predominantly due to immune mechanisms or neurotoxic side effects of drugs used to treat the symptoms of COVID-19 and, to a lesser extent, due to the compression of peripheral nerves resulting from prolonged bedding in the Intensive Care Unit (ICU) and pre-existing risk factors such as diabetes. SARS-CoV-2 does not cause viral neuropathy. Neurotoxic drugs such as daptomycin, linezolid, lopinavir, ritonavir, hydro-chloroquine, cisatracurium, clindamycin, and glucocorticoids should be administered with caution and patients should be appropriately bedded in the ICU to prevent SARS-CoV-2-associated neuropathy. Patients with Guillain-Barré syndrome (GBS) benefit from immunoglobulins, plasma exchange, and steroids. Conclusions: Neuropathies of peripheral nerves in patients with COVID-19 are frequent and mostly result from immune mechanisms or neurotoxic side effects of drugs used to treat the symptoms of COVID-19 and, to a lesser extent, from the compression of peripheral nerves due to prolonged bedding on the ICU. SARS-CoV-2 does not cause infectious neuropathy.

RESUMO Introdução: A presente minirrevisão tem como objetivo resumir e discutir os avanços dos aspectos clínicos, fisiopatológicos, de diagnóstico, tratamento e evolução das neuropatias dos nervos periféricos associadas à COVID-19. Métodos: Revisão da literatura. Resultados: Foram avaliados 105 artigos sobre neuropatia associada à COVID-19. Nesses estudos, 261 pacientes apresentaram boa evolução. As neuropatias dos nervos periféricos em pacientes com COVID-19 são frequentes e se devem, principalmente, aos mecanismos immunológicos ou efeitos colaterais neurotóxicos dos medicamentos utilizados para o tratamento da COVID-19, a fatores de risco pré-existentes, como diabetes e, em menor parte, à compressão dos nervos periféricos nos leitos da UTI. A COVID-19 não causa neuropatia viral. Os medicamentos neurotóxicos, como daptomicina, linezolida, lopinavir, ritonavir, hidro-cloroquina, cisatracúrio, clindamicina e glicocorticoides devem ser administrados com cautela, e os pacientes deve ser adequadamente admitidos nos leitos da UTI para prevenir o desenvolvimento de neuropatia associada à COVID-19. Pacientes com síndrome de Guillain-Barré (GBS) se beneficiam de imunoglobulinas, plasmaférese e esteroides. Conclusões: As neuropatias dos nervos periféricos em pacientes com COVID-19 são raras e predominantemente devidas aos efeitos colaterais neurotóxicos das mecanismos immunológicos ou drogas utilizadas para o tratamento de COVID-19 e, em menor parte, devido à compressão dos nervos periféricos nos leitos da UTI. A COVID-19 não causa neuropatia infeciosa.

Cardioprotection stimulated by resveratrol and grape products prevents lethal cardiac arrhythmias in an animal model of ischemia and reperfusion

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.

New Brazilian variant of the SARS-CoV-2 (P1/Gamma) of COVID-19 in Alagoas state

ABSTRACT Since the beginning of 2020, health authorities have been monitoring the cases of Coronavirus Disease 2019 (COVID-19), which has grown every day in Brazil and around the world, becoming pandemic. The new coronavirus, also called SARS-CoV-2 by scientists spreads rapidly, causing fear, deaths, and threats for the economy of several countries. This work aimed to describe the clinical characterization of the first cases of a new Brazilian variant of SARS-CoV-2 (P1) in the State of Alagoas, which occurred on February 16th, 2021. Two cases are described: first, a person infected in Amazonas State, where the new variant P1 was first described, who migrated to Alagoas State, and second, a case of probable community transmission within Alagoas, since the patient had no history of recent travel. In both confirmed cases the symptoms were mild. Further studies are necessary to better understand the clinical behavior of P1 SARS-CoV-2 variant and also the associated sequelae in the context of COVID-19.