Cardiac autonomic control in the obstructive sleep apnea

Introduction: The sympathetic activation is considered to be the main mechanism involved in the development of cardiovascular diseases in obstructive sleep apnea (OSA). The heart rate variability (HRV) analysis represents a non-invasive tool allowing the study of the autonomic nervous system. The impairment of HRV parameters in OSA has been documented. However, only a few studies tackled the dynamics of the autonomic nervous system during sleep in patients having OSA.Aims: To analyze the HRVover sleep stages and across sleep periods in order to clarify the impact of OSA on cardiac autonomic modulation. The second objective is to examine the nocturnal HRV of OSA patients to find out which HRV parameter is the best to reflect the symptoms severity.Methods: The study was retrospective. We have included 30 patients undergoing overnight polysomnography. Subjects were categorized into two groups according to apneahypopnea index (AHI): mild-to-moderate OSAS group (AHI: 5-30) and severe OSAS group (AHI>30). The HRV measures for participants with low apneahypopnea indices were compared to those of patients with high rates of apneahypopnea across the sleep period and sleep stages.Results: HRV measures during sleep stages for the group with low rates of apneahypopnea have indicated a parasympathetic activation during non-rapid eye movement (NREM) sleep. However, no significant difference has been observed in the high AHI group except for the mean of RR intervals (mean RR). The parasympathetic activity tended to increase across the night but without a statistical difference. After control of age and body mass index, the most significant correlation found was for the mean RR (p =0.0001, r = -0.248).Conclusion: OSA affects sympathovagal modulation during sleep, and this impact has been correlated to the severity of the disease. The mean RR seemed to be a better index allowing the sympathovagal balance appreciation during the night in OSA.Keywords: autonomic nervous system; sleep apnea; heart rate; sleep; circadia

Pituitary Adenylate Cyclase Activating Peptide (1-38) and its analog (Acetyl-[Ala15, Ala20] PACAP 38-polyamide) reverse methacholine airway hyperresponsiveness in rats

O objetivo deste estudo foi investigar funcionalmente e estruturalmente efeito broncodilatador do peptídeo ativador da adenilato ciclase pituitária (PACAP1-38) e da acetil-[Ala15, Ala20]PACAP 38-poliamida, potente análogo do PACAP-38, nos ratos desafiados pelo metacolina (MeCh). Ratos Wistar machos foram aleatoriamente divididos em cinco grupos. Grupos 1 e 2, inalando aerossóis de solução salina ou doses crescentes de MeCh (0,5, 1, 2,12, 4,25, 8,5, 17, 34 e 68 mg/L). Os outros grupos recebendo terbutalina (Terb) (250 µg/rato) (10-6M), PACAP-38 (50 µg/rato) (0.1 mM) ou análogo do PACAP-38 (50 µg/rato) associados a MeCh na dose de 4,25 mg/L. A resistência pulmonar total (RL) foi registrada antes e 2 min após a administração de Mech pelo equipamento pneumomultiteste. A administração MeCh induziu aumento significativo e dose dependente (pThe aim of this study was to investigate both functionally and structurally bronchodilator effects of Pituitary adenylate cyclase activating peptide (PACAP38) and acetyl-[Ala15, Ala20] PACAP38-polyamide, a potent PACAP38 analog, in rats challenged by methacholine (MeCh). Male Wistar rats were divided randomly into five groups. Groups 1 and 2 inhaled respectively aerosols of saline or increasing doses of MeCh (0.5, 1, 2.12, 4.25, 8.5, 17, 34 and 68mg/L). The other groups received terbutaline (Terb) (250 µg/rat) (10-6 M), PACAP38 (50 µg/rat) (0.1 mM) or PACAP38 analog (50 µg/rat) associated to MeCh from the dose of 4.25 mg/L. Total lung resistances (RL) were recorded before and 2 min after MeCh administration by pneumomultitest equipment. MeCh administration induced a significant and a dose-dependent increase (

Astrocyte-Derived Tissue Transglutaminase Interacts with Fibronectin: A Role in Astrocyte Adhesion and Migration?

An important neuropathological feature of neuroinflammatory processes that occur during e.g. Multiple Sclerosis (MS) is the formation of an astroglial scar. Astroglial scar formation is facilitated by the interaction between astrocytes and extracellular matrix proteins (ECM) such as fibronectin. Since there is evidence indicating that glial scars strongly inhibit both axon growth and (re)myelination in brain lesions, it is important to understand the factors that contribute to the interaction between astrocytes and ECM proteins. Tissue Transglutaminase (TG2) is a multifunctional enzyme with an ubiquitous tissue distribution, being clearly present within the brain. It has been shown that inflammatory cytokines can enhance TG2 activity. In addition, TG2 can mediate cell adhesion and migration and it binds fibronectin with high affinity. We therefore hypothesized that TG2 is involved in astrocyte-fibronectin interactions. Our studies using primary rat astrocytes show that intracellular and cell surface expression and activity of TG2 is increased after treatment with pro-inflammatory cytokines. Astrocyte-derived TG2 interacts with fibronectin and is involved in astrocyte adhesion onto and migration across fibronectin. TG2 is involved in stimulating focal adhesion formation which is necessary for the interaction of astrocytes with ECM proteins. We conclude that astrocyte-derived TG2 contributes to the interaction between astrocytes and fibronectin. It might thereby regulate ECM remodeling and possibly glial scarring