Electrical stimulation as a promising therapeutic in inflammatory bowel disease: a scoping review / estimulação: Elétrica como terapêutica promissora na doença inflamatória intestinal: uma revisão de escopo

The central nervous system has extensive innervation spread to the gastrointestinal tract, providing the possibility for using nerve stimulation to treat gastrointestinal diseases, such as Inflammatory Bowel Disease (IBD). This review aimed to carry out a bibliographic survey of the primary clinical studies that correlate IBD treatment with neural electrical stimulation. The following databases were consulted: PubMed, Embase, Cochrane, and BioMed. A total of 477 articles were screened at the titles and abstract level, of which 210 were also assessed at the full text for eligibility. The eleven articles identified for inclusion were selected in this review. The search terms used for the search included: "electrical stimulation", "electrical neuromodulation", "inflammatory bowel disease", "ulcerative colitis", and "Crohn’s Disease". The nerves modulate inflammation in the gut, however, the clinical protocols for anti-inflammatory effects have had variable success. There is still little scientific evidence for an accurate clinical decision for using this electroceutical approach. Therefore, further studies are needed to reduce the heterogeneity of clinical protocols

Sural nerve involvement in experimental hypertension: morphology and morphometry in male and female normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR)

<p>Abstract</p> <p>Background</p> <p>The sural nerve has been widely investigated in experimental models of neuropathies but information about its involvement in hypertension was not yet explored. The aim of the present study was to compare the morphological and morphometric aspects of different segments of the sural nerve in male and female spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto (WKY) rats. Rats aged 20 weeks (N = 6 in each group) were investigated. After arterial pressure and heart rate recordings in anesthetized animals, right and left sural nerves were removed and prepared for epoxy resin embedding and light microscopy. Morphometric analysis was performed with the aid of computer software, and took into consideration the fascicle area and diameter, as well as myelinated fiber number, density, area and diameter.</p> <p>Results</p> <p>Significant differences were observed for the myelinated fiber number and density, comparing different genders of WKY and SHR. Also, significant differences for the morphological (thickening of the endoneural blood vessel walls and lumen reduction) and morphometric (myelinated fibers diameter and G ratio) parameters of myelinated fibers were identified. Morphological exam of the myelinated fibers suggested the presence of a neuropathy due to hypertension in both SHR genders.</p> <p>Conclusions</p> <p>These results indicate that hypertension altered important morphometric parameters related to nerve conduction of sural nerve in hypertensive animals. Moreover the comparison between males and females of WKY and SHR allows the conclusion that the morphological and morphometric parameters of sural nerve are not gender related. The morphometric approach confirmed the presence of neuropathy, mainly associated to the small myelinated fibers. In conclusion, the present study collected evidences that the high blood pressure in SHR is affecting the sural nerve myelinated fibers.</p

Investigating autonomic nervous system dysfunction among patients with post-COVID condition and prolonged cardiovascular symptoms

Heart Rate Variability (HRV) and arterial pressure (AP) variability and their responses to head-up tilt test (HUTT) were investigated in Post-COVID-19 syndrome (PCS) patients reporting tachycardia and/or postural hypotension. Besides tachycardia, PCS patients also showed attenuation of the following HRV parameters: RMSSD [square root of the mean of the sum of the squares of differences between adjacent normal-to-normal (NN) intervals] from statistical measures; the power of RR (beat-to-beat interval) spectra at HF (high frequency) from the linear method spectral analysis; occurrence of 2UV (two unlike variation) pattern of RR from the nonlinear method symbolic analysis; and the new family of statistics named sample entropy, when compared to control subjects. Basal AP and LF (low frequency) power of systolic AP were similar between PCS patients and control subjects, while 0 V (zero variation) patterns of AP from the nonlinear method symbolic analysis were exacerbated in PCS patients. Despite tachycardia and a decrease in RMSSD, no parameter of HRV changed during HUTT in PCS patients compared to control subjects. PCS patients reassessed after 6 months showed higher HF power of RR spectra and a higher percentage of 2UV pattern of RR. Moreover, the reassessed PCS patients showed a lower occurrence of 0 V patterns of AP, while the HUTT elicited HR (heart rate) and AP responses identical to control subjects. The HRV and AP variability suggest an autonomic dysfunction with sympathetic predominance in PCS patients. In contrast, the lack of responses of HRV and AP variability indices during HUTT indicates a marked impairment of autonomic control. Of note, the reassessment of PCS patients showed that the noxious effect of COVID-19 on autonomic control tended to fade over time

Rationale, study design, and analysis plan of the Alveolar Recruitment for ARDS Trial (ART): Study protocol for a randomized controlled trial

Background: Acute respiratory distress syndrome (ARDS) is associated with high in-hospital mortality. Alveolar recruitment followed by ventilation at optimal titrated PEEP may reduce ventilator-induced lung injury and improve oxygenation in patients with ARDS, but the effects on mortality and other clinical outcomes remain unknown. This article reports the rationale, study design, and analysis plan of the Alveolar Recruitment for ARDS Trial (ART). Methods/Design: ART is a pragmatic, multicenter, randomized (concealed), controlled trial, which aims to determine if maximum stepwise alveolar recruitment associated with PEEP titration is able to increase 28-day survival in patients with ARDS compared to conventional treatment (ARDSNet strategy). We will enroll adult patients with ARDS of less than 72 h duration. The intervention group will receive an alveolar recruitment maneuver, with stepwise increases of PEEP achieving 45 cmH(2)O and peak pressure of 60 cmH2O, followed by ventilation with optimal PEEP titrated according to the static compliance of the respiratory system. In the control group, mechanical ventilation will follow a conventional protocol (ARDSNet). In both groups, we will use controlled volume mode with low tidal volumes (4 to 6 mL/kg of predicted body weight) and targeting plateau pressure &lt;= 30 cmH2O. The primary outcome is 28-day survival, and the secondary outcomes are: length of ICU stay; length of hospital stay; pneumothorax requiring chest tube during first 7 days; barotrauma during first 7 days; mechanical ventilation-free days from days 1 to 28; ICU, in-hospital, and 6-month survival. ART is an event-guided trial planned to last until 520 events (deaths within 28 days) are observed. These events allow detection of a hazard ratio of 0.75, with 90% power and two-tailed type I error of 5%. All analysis will follow the intention-to-treat principle. Discussion: If the ART strategy with maximum recruitment and PEEP titration improves 28-day survival, this will represent a notable advance to the care of ARDS patients. Conversely, if the ART strategy is similar or inferior to the current evidence-based strategy (ARDSNet), this should also change current practice as many institutions routinely employ recruitment maneuvers and set PEEP levels according to some titration method.Hospital do Coracao (HCor) as part of the Program 'Hospitais de Excelencia a Servico do SUS (PROADI-SUS)'Brazilian Ministry of Healt

Effect of baroreceptor denervation on the autonomic control of arterial pressure in conscious mice

This study evaluated the role of arterial baroreceptors in arterial pressure (AP) and pulse interval (PI) regulation in conscious C57BL mice. Male animals, implanted with catheters in a femoral artery and a jugular vein, were submitted to sino-aortic (SAD), aortic (Ao-X) or carotid sinus denervation (Ca-X), 5 daysprior to the experiments. After basal recording of AP, the lack of reflex bradycardia elicited by administration of phenylephrine was used to confirm the efficacy of SAD, and cardiac autonomic blockade with methylatropine and propranolol was performed. The AP and PI variability were calculated in the time and frequency domains (spectral analysis/fast Fourier transform) with the spectra quantified in low-(LF; 0.25-1Hz) and high-frequency bands (HF; 1-5Hz). Basal AP and AP variability were higher after SAD, Ao-X or Ca-X than in intact mice. Pulse interval was similar among the groups, whereas PI variability was lower after SAD. Atropine elicited a slight tachycardia in control mice but did not change PI after total or partial denervation. The bradycardia caused by propranolol was higher after SAD, Ao-X or Ca-X compared with intact mice. The increase in the variability of AP was accompanied by a marked increase in the LF and HF power of the AP spectra after baroreceptor denervation. The LF and HF power of the PI were reduced by SAD and by Ao-X or Ca-X. Therefore, both sino-aortic and partial baroreceptor denervation in mice elicits hypertension and a remarkable increase in AP variability and cardiac sympathetic tonus. Spectral analysis showed an important contribution of the baroreflex in the power of LF oscillations of the PI spectra. Both sets of baroreceptors seem to be equally important in the autonomic regulation of the cardiovascular system in mice.Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq)Coordenadoria de Aperfeicoamento de Pessoal de Nivel Superior (CAPES

Hemodynamic responses to aortic depressor nerve stimulation in conscious L-NAME-induced hypertensive rats

Durand MT, Castania JA, Fazan R Jr, Salgado MC, Salgado HC. Hemodynamic responses to aortic depressor nerve stimulation in conscious L-NAME-induced hypertensive rats. Am J Physiol Regul Integr Comp Physiol 300: R418-R427, 2011. First published November 24, 2010; doi: 10.1152/ajpregu.00463.2010.-The present study investigated whether baroreflex control of autonomic function is impaired when there is a deficiency in NO production and the role of adrenergic and cholinergic mechanisms in mediating reflex responses. Electrical stimulation of the aortic depressor nerve in conscious normotensive and nitro-L-arginine methyl ester (L-NAME)-induced hypertensive rats was applied before and after administration of methylatropine, atenolol, and prazosin alone or in combination. The hypotensive response to progressive electrical stimulation (5 to 90 Hz) was greater in hypertensive (-27 +/- 2 to -64 +/- 3 mmHg) than in normotensive rats (-17 +/- 1 to -46 +/- 2 mmHg), whereas the bradycardic response was similar in both groups (-34 +/- 5 to -92 +/- 9 and -21 +/- 2 to -79 +/- 7 beats/min, respectively). Methylatropine and atenolol showed no effect in the hypotensive response in either group. Methylatropine blunted the bradycardic response in both groups, whereas atenolol attenuated only in hypertensive rats. Prazosin blunted the hypotensive response in both normotensive (43%) and hypertensive rats (53%) but did not affect the bradycardic response in either group. Prazosin plus angiotensin II, used to restore basal arterial pressure, provided hemodynamic responses similar to those of prazosin alone. The triple pharmacological blockade abolished the bradycardic response in both groups but displayed similar residual hypotensive response in hypertensive (-13 +/- 2 to -27 +/- 2 mmHg) and normotensive rats (-10 +/- 1 to -25 +/- 3 mmHg). In conclusion, electrical stimulation produced a well-preserved baroreflex-mediated decrease in arterial pressure and heart rate in conscious L-NAME-induced hypertensive rats. Moreover, withdrawal of the sympathetic drive played a role in the reflex bradycardia only in hypertensive rats. The residual fall in pressure after the triple pharmacological blockade suggests the involvement of a vasodilatory mechanism unrelated to NO or deactivation of alpha(1)-adrenergic receptor.FAPESP Fundacao de Amparo a Pesquisa do Estado de Sao PauloCNPq Conselho Nacional de Desenvolvimento Cientifico e TecnologicoCAPES Coordenadoria de Aperfeicoamento de Pessoal de Nivel SuperiorPesquisa e Assistencia do H. C. da Faculdade de Medicina de Ribeirao Preto (FAEPA