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1.
Crit Care ; 28(1): 2, 2024 01 02.
Artigo em Inglês | MEDLINE | ID: mdl-38166968

RESUMO

Surface electromyography (sEMG) can be used to measure the electrical activity of the respiratory muscles. The possible applications of sEMG span from patients suffering from acute respiratory failure to patients receiving chronic home mechanical ventilation, to evaluate muscle function, titrate ventilatory support and guide treatment. However, sEMG is mainly used as a monitoring tool for research and its use in clinical practice is still limited-in part due to a lack of standardization and transparent reporting. During this round table meeting, recommendations on data acquisition, processing, interpretation, and potential clinical applications of respiratory sEMG were discussed. This paper informs the clinical researcher interested in respiratory muscle monitoring about the current state of the art on sEMG, knowledge gaps and potential future applications for patients with respiratory failure.


Assuntos
Músculo Esquelético , Músculos Respiratórios , Humanos , Eletromiografia , Músculos Respiratórios/fisiologia , Músculo Esquelético/fisiologia
2.
Sci Rep ; 13(1): 22134, 2023 12 13.
Artigo em Inglês | MEDLINE | ID: mdl-38092785

RESUMO

Mucormycosis is a severe complication in critically ill COVID-19 patients. Throughout the pandemic, a notable prevalence of mucormycosis has been observed in the Indian population, whereas lower occurrences have been reported in Europe. However, limited data exist regarding its prevalence in Europe, which is potentially underestimated due to the low sensitivity of bronchoalveolar lavage (BAL) cultures. We aimed to evaluate the prevalence of mucormycosis in a high-risk critically ill COVID-19 population in the Netherlands, and to evaluate the potential benefit of adding Mucor PCR to BAL as part of routine follow-up. In this study, we included 1035 critically ill COVID-19 patients admitted to either one of the two ICUs at AmsterdamUMC between March 2020 and May 2022; of these, 374 had undergone at least one bronchoscopy. Following the AmsterdamUMC protocols, bronchoscopies were conducted weekly until clinical improvement was achieved. We cultured BAL fluid for fungi and used PCR and galactomannan testing to detect Aspergillus spp. Additionally, we retrospectively performed qPCR targeting Mucorales DNA in the BAL of 89 deceased patients. All cultures were negative for Mucorales, whereas 42 (11%) cultures were positive for Aspergillus. Furthermore, qPCR targeting Mucorales was negative in all 89 deceased patients. This study showed that pulmonary mucormycosis was not present in critically ill COVID-19 patients in two tertiary care ICUs. These results indicate routine Mucorales qPCR screening is not clinically necessary in a high-standard-of-care tertiary ICU in a low-endemic area.


Assuntos
COVID-19 , Mucorales , Mucormicose , Humanos , Mucormicose/epidemiologia , Países Baixos/epidemiologia , Estado Terminal , Estudos Retrospectivos , COVID-19/epidemiologia , Mucorales/genética , Aspergillus/genética , Unidades de Terapia Intensiva
3.
Crit Care ; 27(1): 268, 2023 07 06.
Artigo em Inglês | MEDLINE | ID: mdl-37415253

RESUMO

BACKGROUND: Individualised optimisation of mechanical ventilation (MV) remains cumbersome in modern intensive care medicine. Computerised, model-based support systems could help in tailoring MV settings to the complex interactions between MV and the individual patient's pathophysiology. Therefore, we critically appraised the current literature on computational physiological models (CPMs) for individualised MV in the ICU with a focus on quality, availability, and clinical readiness. METHODS: A systematic literature search was conducted on 13 February 2023 in MEDLINE ALL, Embase, Scopus and Web of Science to identify original research articles describing CPMs for individualised MV in the ICU. The modelled physiological phenomena, clinical applications, and level of readiness were extracted. The quality of model design reporting and validation was assessed based on American Society of Mechanical Engineers (ASME) standards. RESULTS: Out of 6,333 unique publications, 149 publications were included. CPMs emerged since the 1970s with increasing levels of readiness. A total of 131 articles (88%) modelled lung mechanics, mainly for lung-protective ventilation. Gas exchange (n = 38, 26%) and gas homeostasis (n = 36, 24%) models had mainly applications in controlling oxygenation and ventilation. Respiratory muscle function models for diaphragm-protective ventilation emerged recently (n = 3, 2%). Three randomised controlled trials were initiated, applying the Beacon and CURE Soft models for gas exchange and PEEP optimisation. Overall, model design and quality were reported unsatisfactory in 93% and 21% of the articles, respectively. CONCLUSION: CPMs are advancing towards clinical application as an explainable tool to optimise individualised MV. To promote clinical application, dedicated standards for quality assessment and model reporting are essential. Trial registration number PROSPERO- CRD42022301715 . Registered 05 February, 2022.


Assuntos
Pulmão , Respiração Artificial , Humanos , Cuidados Críticos , Fenômenos Fisiológicos Respiratórios
4.
J Crit Care ; 73: 154173, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36265246

RESUMO

PURPOSE: To examine whether lung ultrasound prior to prone positioning can predict the resulting gas-exchange response. MATERIALS AND METHODS: This is a prospective observational study on critically-ill COVID-19 patients with a pilot and confirmation cohort. Lung ultrasound examinations were performed before prone positioning and gas-exchange parameters were recorded before and after position change. RESULTS: A total of 79 patients, 36 in the pilot cohort and 43 in the confirmation cohort, were included. In the pilot cohort, a moderate correlation between pre-turn lung ultrasound score index (LUSI) and change in PaO2/FiO2 after prone positioning was found. These findings were corroborated and extended upon in the confirmation cohort. The confirmation cohort found that anterior LUSI had the strongest correlation with follow-up time-points 1, 6, 12, and 24 h after prone positioning, with strength of correlation gradually increasing up to 24 h. In a multivariate model anterior aeration loss (odds ratio 0.035; 95%CI 0.003-0.319 for anterior LUSI >50%) and higher pre-turn PaCO2 (odds ratio 0.479 95% CI 0.235-0.979) were negatively predictive of a PaO2/FiO2 increase ≥20 mmHg. CONCLUSIONS: Anterior LUSI, in addition to other clinical parameters, may be used to aid COVID-19 respiratory strategy and a clinician's decision to prone.


Assuntos
COVID-19 , Síndrome do Desconforto Respiratório , Humanos , Decúbito Ventral/fisiologia , Estudos Prospectivos , Respiração com Pressão Positiva/métodos , Troca Gasosa Pulmonar/fisiologia , Pulmão/diagnóstico por imagem , Respiração Artificial
5.
Ann Intensive Care ; 11(1): 167, 2021 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-34862945

RESUMO

BACKGROUND: Dynamic pulmonary hyperinflation may develop in patients with chronic obstructive pulmonary disease (COPD) due to dynamic airway collapse and/or increased airway resistance, increasing the risk of volutrauma and hemodynamic compromise. The reference standard to quantify dynamic pulmonary hyperinflation is the measurement of the volume at end-inspiration (Vei). As this is cumbersome, the aim of this study was to evaluate if methods that are easier to perform at the bedside can accurately reflect Vei. METHODS: Vei was assessed in COPD patients under controlled protective mechanical ventilation (7 ± mL/kg) on zero end-expiratory pressure, using three techniques in a fixed order: (1) reference standard (Veireference): passive exhalation to atmosphere from end-inspiration in a calibrated glass burette; (2) ventilator maneuver (Veimaneuver): measuring the expired volume during a passive exhalation of 45s using the ventilator flow sensor; (3) formula (Veiformula): (Vt × Pplateau)/(Pplateau - PEEPi), with Vt tidal volume, Pplateau is plateau pressure after an end-inspiratory occlusion, and PEEPi is intrinsic positive end-expiratory pressure after an end-expiratory occlusion. A convenience sample of 17 patients was recruited. RESULTS: Veireference was 1030 ± 380 mL and had no significant correlation with Pplateau (r2 = 0.06; P = 0.3710) or PEEPi (r2 = 0.11; P = 0.2156), and was inversely related with Pdrive (calculated as Pplateau -PEEPi) (r2 = 0.49; P = 0.0024). A low bias but rather wide limits of agreement and fairly good correlations were found when comparing Veimaneuver and Veiformula to Veireference. Vei remained stable during the study period (low bias 15 mL with high agreement (95% limits of agreement from - 100 to 130 mL) and high correlation (r2 = 0.98; P < 0.0001) between both measurements of Veireference). CONCLUSIONS: In patients with COPD, airway pressures are not a valid representation of Vei. The three techniques to quantify Vei show low bias, but wide limits of agreement.

6.
Ann Intensive Care ; 10(1): 67, 2020 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-32472272

RESUMO

BACKGROUND: Inappropriate ventilator assist plays an important role in the development of diaphragm dysfunction. Ventilator under-assist may lead to muscle injury, while over-assist may result in muscle atrophy. This provides a good rationale to monitor respiratory drive in ventilated patients. Respiratory drive can be monitored by a nasogastric catheter, either with esophageal balloon to determine muscular pressure (gold standard) or with electrodes to measure electrical activity of the diaphragm. A disadvantage is that both techniques are invasive. Therefore, it is interesting to investigate the role of surrogate markers for respiratory dive, such as extradiaphragmatic inspiratory muscle activity. The aim of the current study was to investigate the effect of different inspiratory support levels on the recruitment pattern of extradiaphragmatic inspiratory muscles with respect to the diaphragm and to evaluate agreement between activity of extradiaphragmatic inspiratory muscles and the diaphragm. METHODS: Activity from the alae nasi, genioglossus, scalene, sternocleidomastoid and parasternal intercostals was recorded using surface electrodes. Electrical activity of the diaphragm was measured using a multi-electrode nasogastric catheter. Pressure support (PS) levels were reduced from 15 to 3 cmH2O every 5 min with steps of 3 cmH2O. The magnitude and timing of respiratory muscle activity were assessed. RESULTS: We included 17 ventilated patients. Diaphragm and extradiaphragmatic inspiratory muscle activity increased in response to lower PS levels (36 ± 6% increase for the diaphragm, 30 ± 6% parasternal intercostals, 41 ± 6% scalene, 40 ± 8% sternocleidomastoid, 43 ± 6% alae nasi and 30 ± 6% genioglossus). Changes in diaphragm activity correlated best with changes in alae nasi activity (r2 = 0.49; P < 0.001), while there was no correlation between diaphragm and sternocleidomastoid activity. The agreement between diaphragm and extradiaphragmatic inspiratory muscle activity was low due to a high individual variability. Onset of alae nasi activity preceded the onset of all other muscles. CONCLUSIONS: Extradiaphragmatic inspiratory muscle activity increases in response to lower inspiratory support levels. However, there is a poor correlation and agreement with the change in diaphragm activity, limiting the use of surface electromyography (EMG) recordings of extradiaphragmatic inspiratory muscles as a surrogate for electrical activity of the diaphragm.

7.
Respir Physiol Neurobiol ; 249: 47-53, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29307724

RESUMO

BACKGROUND: Patients with acute respiratory failure may develop respiratory acidosis. Metabolic compensation by bicarbonate production or retention results in posthypercapnic alkalosis with an increased arterial bicarbonate concentration. The hypothesis of this study was that elevated plasma bicarbonate levels decrease respiratory drive and minute ventilation. METHODS: In an intervention study in 10 healthy subjects the ventilatory response using a hypercapnic ventilatory response (HCVR) test was assessed, before and after administration of high dose sodium bicarbonate. Total dose of sodiumbicarbonate was 1000 ml 8.4% in 3 days. RESULTS: Plasma bicarbonate increased from 25.2 ±â€¯2.2 to 29.2 ±â€¯1.9 mmol/L. With increasing inspiratory CO2 pressure during the HCVR test, RR, Vt, Pdi, EAdi and VE increased. The clinical ratio ΔVE/ΔPetCO2 remained unchanged, but Pdi, EAdi and VE were significantly lower after bicarbonate administration for similar levels of inspired CO2. CONCLUSION: This study demonstrates that in healthy subjects metabolic alkalosis decreases the neural respiratory drive and minute ventilation, as a response to inspiratory CO2.


Assuntos
Bicarbonatos/sangue , Respiração/efeitos dos fármacos , Bicarbonato de Sódio/farmacologia , Adulto , Análise de Variância , Feminino , Voluntários Saudáveis , Humanos , Masculino , Respiração Artificial , Testes de Função Respiratória , Fatores de Tempo , Adulto Jovem
8.
Acta Anaesthesiol Scand ; 58(4): 487-94, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24571360

RESUMO

BACKGROUND: Mechanical ventilation (MV) can result in inflammation and subsequent lung injury. Toll-like receptor (TLR)4 and NF-κB are proposed to play a crucial role in the MV-induced inflammatory response. Resveratrol (RVT) exhibits anti-inflammatory effects in vitro and in vivo supposedly by interfering with TLR4 signaling and NF-κB. In the present study, we investigated the role of RVT in MV-induced inflammation in mice. METHODS: RVT (10 mg/kg, 20 mg/kg and 40 mg/kg) or vehicle was intraperitoneally administered 1 h before start of MV (4 h, tidal volume 8 ml/kg, positive end-expiratory pressure 1,5 cmH2 O and FiO2 0.4). Blood and lungs were harvested for cytokine analysis. DNA binding activity of transcription factor NF-κB was measured in lung homogenates. RESULTS: MV resulted in elevated pulmonary concentrations of IL-1ß, IL-6, keratinocyte-derived chemokine (KC) and NF-κB DNA-binding activity. RVT at 10, 20 and 40 mg/kg reduced NF-κB's DNA-binding activity following MV compared with ventilated controls. However, no differences in cytokine release were found between RVT-treated and control ventilated mice. Similarly, in plasma, MV resulted in elevated concentrations of TNF-α, KC and IL-6, but RVT did not affect cytokine levels. CONCLUSIONS: RVT abrogates the MV-induced increase in pulmonary NF-κB activity but does not attenuate cytokine levels. This implies a less prominent role for NF-κB in MV-induced inflammation than previously assumed.


Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Citocinas/biossíntese , NF-kappa B/efeitos dos fármacos , NF-kappa B/metabolismo , Respiração Artificial , Estilbenos/farmacologia , Animais , Citocinas/análise , DNA/metabolismo , Ensaio de Imunoadsorção Enzimática , Coração/efeitos dos fármacos , Coração/fisiologia , Pulmão/efeitos dos fármacos , Pulmão/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Resveratrol
9.
Heart Lung Vessel ; 5(4): 227-45, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24364017

RESUMO

Levosimendan is an inodilator indicated for the short-term treatment of acutely decompensated severe chronic heart failure, and in situations where conventional therapy is not considered adequate. The principal pharmacological effects of levosimendan are (a) increased cardiac contractility by calcium sensitisation of troponin C, (b) vasodilation, and (c) cardioprotection. These last two effects are related to the opening of sarcolemmal and mitochondrial potassium-ATP channels, respectively. Data from clinical trials indicate that levosimendan improves haemodynamics with no attendant significant increase in cardiac oxygen consumption and relieves symptoms of acute heart failure; these effects are not impaired or attenuated by the concomitant use of beta-blockers. Levosimendan also has favourable effects on neurohormone levels in heart failure patients. Levosimendan is generally well tolerated in acute heart failure patients: the most common adverse events encountered in this setting are hypotension, headache, atrial fibrillation, hypokalaemia and tachycardia. Levosimendan has also been studied in other therapeutic applications, particularly cardiac surgery - in which it has shown a range of beneficial haemodynamic and cardioprotective effects, and a favourable influence on clinical outcomes - and has been evaluated in repetitive dosing protocols in patients with advanced chronic heart failure. Levosimendan has shown preliminary positive effects in a range of conditions requiring inotropic support, including right ventricular failure, cardiogenic shock, septic shock, and Takotsubo cardiomyopathy.

10.
Br J Pharmacol ; 162(3): 566-73, 2011 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-20880026

RESUMO

BACKGROUND AND PURPOSE: Diaphragm muscle weakness occurs in patients with heart failure (HF) and is associated with exercise intolerance and increased mortality. Reduced sensitivity of diaphragm fibres to calcium contributes to diaphragm weakness in HF. Here we have investigated the ability of the calcium sensitizer levosimendan to restore the reduced calcium sensitivity of diaphragm fibres from rats with HF. EXPERIMENTAL APPROACH: Coronary artery ligation in rats was used as an animal model for HF. Sham-operated rats served as controls. Fifteen weeks after induction of HF or sham operations animals were killed and muscle fibres were isolated from the diaphragm. Diaphragm fibres were skinned and activated with solutions containing incremental calcium concentrations and 10 µM levosimendan or vehicle (0.02% DMSO). Developed force was measured at each calcium concentration, and force-calcium concentration relationships were plotted. KEY RESULTS: Calcium sensitivity of force generation was reduced in diaphragm muscle fibres from HF rats, compared with fibres from control rats (P < 0.01). Maximal force generation was ∼25% lower in HF diaphragm fibres than in control fibres (P < 0.05). Levosimendan significantly increased calcium sensitivity of force generation in diaphragm fibres from HF and control rats, without affecting maximal force generation. CONCLUSIONS AND IMPLICATIONS: Levosimendan enhanced the force generating capacity of diaphragm fibres from HF rats by increasing the sensitivity of force generation to calcium concentration. These results provide strong support for testing the effect of calcium sensitizers on diaphragm muscle weakness in patients with HF.


Assuntos
Antiarrítmicos/farmacologia , Cálcio/farmacologia , Diafragma/fisiologia , Insuficiência Cardíaca/fisiopatologia , Hidrazonas/farmacologia , Contração Muscular/efeitos dos fármacos , Fibras Musculares Esqueléticas/efeitos dos fármacos , Piridazinas/farmacologia , Animais , Diafragma/efeitos dos fármacos , Humanos , Masculino , Fibras Musculares Esqueléticas/química , Fibras Musculares Esqueléticas/fisiologia , Debilidade Muscular , Cadeias Pesadas de Miosina/análise , Ratos , Ratos Wistar , Simendana
11.
Int J Cardiol ; 141(3): 275-83, 2010 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-19150150

RESUMO

BACKGROUND: Diaphragm dysfunction is well-known to limit quality of life and prognosis of patients with heart failure (HF), but its underlying mechanisms are not well understood. In an animal model for HF we recently showed that impaired diaphragm contractility arises at the single fiber level and is associated with sarcomeric injuries. For optimal muscle function and sarcomeric stability passive elastic structures, like titin, are indispensable. The current study aimed to investigate if impaired passive elasticity contributes to diaphragm dysfunction in rats with heart failure. METHODS: Skinned muscle fibers were isolated from the diaphragm and soleus of rats with chronic HF, induced by left coronary artery ligation and of sham-operated rats. Passive tension-length relationships were determined by applying segmental extension tests. Immunofluorescence was performed on muscle cryosections using antibodies (T12) against a titin epitope near the Z-line. Titin content was determined by SDS-agarose-gel electrophoresis. Titin's mobility on gel was studied to detect changes in titin size. RESULTS: Passive tension generation upon stretch was significantly reduced (>35%) in HF diaphragm fibers compared to sham. Immunostaining intensities against titin were reduced in diaphragm cryosections of HF rats compared to sham. Soleus fibers from HF and sham rats did not display differences, neither in passive tension nor in immunostaining. No differences in titin's size were detected in HF and sham diaphragm. Titin content, however, was significantly reduced ( approximately 25%) in HF diaphragm. DISCUSSION: We conclude that in the diaphragm of HF rats, passive elasticity is impaired, mainly resulting from titin loss.


Assuntos
Diafragma/fisiopatologia , Insuficiência Cardíaca/fisiopatologia , Fibras Musculares Esqueléticas/fisiologia , Proteínas Musculares/metabolismo , Tono Muscular/fisiologia , Animais , Conectina , Diafragma/citologia , Diafragma/metabolismo , Modelos Animais de Doenças , Elasticidade , Eletroforese em Gel de Ágar , Imunofluorescência , Masculino , Peso Molecular , Contração Muscular/fisiologia , Fibras Musculares Esqueléticas/metabolismo , Proteínas Musculares/química , Músculo Esquelético/citologia , Músculo Esquelético/metabolismo , Músculo Esquelético/fisiopatologia , Cadeias Pesadas de Miosina/metabolismo , Ratos , Ratos Wistar
12.
Acta Anaesthesiol Scand ; 53(6): 742-8, 2009 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-19388896

RESUMO

BACKGROUND: Mechanical ventilation (MV) induces an inflammatory response in healthy lungs. The resulting pro-inflammatory state is a risk factor for ventilator-induced lung injury and peripheral organ dysfunction. Isoflurane is known to have protective immunological effects on different organ systems. We tested the hypothesis that the MV-induced inflammatory response in healthy lungs is reduced by isoflurane. METHODS: Healthy C57BL6 mice (n=34) were mechanically ventilated (tidal volume, 8 ml/kg; positive end-expiratory pressure, 4 cmH(2)O; and fraction of inspired oxygen, 0.4) for 4 h under general anesthesia using a mix of ketamine, medetomidine and atropine (KMA). Animals were divided into four groups: (1) Unventilated control group; (2) MV group using KMA anesthesia; (3) MV group using KMA with 0.25 MAC isoflurane; (4) MV group using KMA with 0.75 MAC isoflurane. Cytokine levels were measured in lung homogenate and plasma. Leukocytes were counted in lung tissue. RESULTS: Lung homogenates: MV increased pro-inflammatory cytokines. In mice receiving KMA+ isoflurane 0.75 MAC, no significant increase in interleukin (IL)-1beta was found compared with non-ventilated control mice. PLASMA: MV induced a systemic pro-inflammatory response. In mice anesthetized with KMA+ isoflurane (both 0.25 and 0.75 MAC), no significant increase in tumor necrosis factor (TNF)-alpha was found compared with non-ventilated control mice. CONCLUSIONS: The present study is the first to show that isoflurane attenuates the pulmonary IL-1beta and systemic TNF-alpha response following MV in healthy mice.


Assuntos
Anestésicos Inalatórios/farmacologia , Interleucina-1beta/metabolismo , Isoflurano/farmacologia , Pulmão/metabolismo , Respiração Artificial , Fator de Necrose Tumoral alfa/metabolismo , Animais , Atropina/farmacologia , Pressão Sanguínea/efeitos dos fármacos , Antagonistas de Aminoácidos Excitatórios/farmacologia , Hipnóticos e Sedativos/farmacologia , Ketamina/farmacologia , Contagem de Leucócitos , Pulmão/efeitos dos fármacos , Masculino , Medetomidina/farmacologia , Camundongos , Camundongos Endogâmicos C57BL , Antagonistas Muscarínicos/farmacologia , Pneumonia/patologia
14.
Eur Respir J ; 30(1): 80-9, 2007 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-17392321

RESUMO

In the present study, phage display-derived antibodies were used to investigate the topology of glycosaminoglycan epitopes in the diaphragm of chronic obstructive pulmonary disease (COPD) and non-COPD patients. Furthermore, the potential physiological significance of changes in the occurrence of glycosaminoglycan epitopes in the diaphragm of COPD patients was studied by determining the overlap in epitope recognition of glycosaminoglycan antibodies and growth factors. Diaphragm cryosections from non-COPD (n = 5) and COPD patients (Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage I/II; n = 9) were incubated with antibodies directed against heparan sulphate, chondroitin sulphate and dermatan sulphate epitopes. Antibodies were visualised immunofluorescently. In addition, interference of antibody and growth factor binding with heparan sulphate epitopes was tested. Specific glycosaminoglycan epitopes showed increased expression in the diaphragm of COPD patients, whereas other epitopes were decreased or unaffected. Interestingly, the anti-heparan sulphate antibody HS4C3, which is directed against a downregulated epitope, interfered with the binding of hepatocyte growth factor. Three patients with the most severe airway obstruction also demonstrated interference of heparan sulphate antibody A04B08 with hepatocyte growth factor binding. Results indicate changes in glycosaminoglycan composition in the diaphragm of patients with chronic obstructive pulmonary disease. This may affect cellular physiology via alterations in growth factor handling and might be related to reduced levels of contractile protein in the diaphragm of these patients.


Assuntos
Diafragma/patologia , Heparitina Sulfato/metabolismo , Doença Pulmonar Obstrutiva Crônica/complicações , Doença Pulmonar Obstrutiva Crônica/patologia , Idoso , Epitopos/química , Feminino , Glicosaminoglicanos/química , Heparitina Sulfato/química , Fator de Crescimento de Hepatócito/metabolismo , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/química , Pneumopatias/patologia , Masculino , Microscopia de Fluorescência , Pessoa de Meia-Idade , Contração Muscular , Biblioteca de Peptídeos
15.
Eur J Appl Physiol ; 88(4-5): 417-26, 2003 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-12527972

RESUMO

Hypoxia disturbs Ca(2+) regulation and increases the intracellular Ca(2+) concentration ([Ca(2+)](i)), which may in turn activate the nitric oxide synthase (NOS) regulated by [Ca(2+)](i). Since nitric oxide (NO) reduces the isometric contractility of rat diaphragm in vitro, we hypothesized that NO contributes to the impaired force generation of an hypoxic diaphragm. The effects of different concentrations of the NOS inhibitor, N(G)-monomethyl-L-arginine (L-NMMA), the NO scavenger haemoglobin (150 micro mol.l(-1)) and the NO donor spermine NONOate (Sp-NO; 1 mmol.l(-1)) were determined on isometric contractility during hypoxia [partial pressure of oxygen, PO(2), about 7 kPa (about 54 mmHg)] and hyperoxia [ PO(2) about 83 kPa (about 639 mmHg)]. Hypoxia significantly reduced maximal twitch force ( F(t)), and submaximal tetanic force (30 Hz, F(30)) in all L-NMMA groups. A low concentration of L-NMMA (30 micromol.l(-1)) increased F(30) but a high concentration (1,000 micromol.l(-1)) reduced F(30) during hypoxia. The effects of L-NMMA on force generation were more pronounced during hypoxia compared to hyperoxia. Peak increases in F(30) and F(t) were observed at a concentration of 30 micromol.l(-1) L-NMMA during hypoxia, but with 10 micromol.l(-1) L-NMMA during hyperoxia. The same concentration of haemoglobin increased F(30) and F(t) less during hypoxia compared to hyperoxia. The Sp-NO reduced F(t), F(30) and maximal tetanic force (F(0)) during hypoxia; these effects were abolished in the presence of haemoglobin. The Sp-NO did not alter F(t), F(30) and F(0)during hyperoxia. We conclude that NO plays a more prominent role during hypoxia and that NO contributes to the depression of force generation in the hypoxic rat diaphragm in vitro. This change may be related to an elevated NO generation within the hypoxic diaphragm.


Assuntos
Diafragma/fisiopatologia , Hipóxia/fisiopatologia , Contração Isométrica , Óxido Nítrico/metabolismo , Espermina/análogos & derivados , Animais , Relação Dose-Resposta a Droga , Inibidores Enzimáticos/administração & dosagem , Hemoglobinas/farmacologia , Hiperóxia/fisiopatologia , Técnicas In Vitro , Contração Isométrica/efeitos dos fármacos , Masculino , Doadores de Óxido Nítrico/farmacologia , Óxidos de Nitrogênio , Concentração Osmolar , Ratos , Ratos Wistar , Espermina/farmacologia , ômega-N-Metilarginina/administração & dosagem
16.
Acta Physiol Scand ; 173(3): 313-21, 2001 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-11736693

RESUMO

Hypoxia is known to reduce isometric contractile properties of isolated rat diaphragm bundles. Its effect on isotonic contractile properties (i.e. force-velocity relationship and power output) has not been studied. We hypothesized that hypoxia reduces velocity of shortening and consequently power output of the unfatigued muscle, and shortens endurance time during isotonic contractions. Force-velocity relationship, power output, and fatigue resistance of rat diaphragm muscle bundles were measured during hypoxia (PO2: 6.6 +/- 0.2 kPa) and compared with hyperoxia (PO2: 91.8 +/- 0.7 kPa). Force was clamped from 1 to 100% of maximal tetanic force (Po). Fatigue during isotonic contractions was induced by repeated stimulation every 2 s at a clamp level of 33% of Po. Hypoxia did not affect isometric force generation compared with hyperoxia, nor contraction or relaxation time. In contrast, maximum shortening velocity decreased significantly (hypoxia: 4.2 +/- 0.3, hyperoxia: 6.0 +/- 0.2 Lo/s, P < 0.05). The force-velocity curve shifted downwards (P < 0.05). Hypoxia lowered power output at each load compared with hyperoxia (P < 0.05). The isotonic endurance time was shorter during hypoxia compared with hyperoxia (80 +/- 2 vs. 130 +/- 3 s, P < 0.05). These data show that hypoxia depresses isotonic contractile properties and power output, and reduces endurance time during repeated isotonic contractions.


Assuntos
Diafragma/fisiologia , Hipóxia/fisiopatologia , Contração Isométrica/fisiologia , Contração Isotônica/fisiologia , Animais , Hiperóxia/fisiopatologia , Masculino , Fadiga Muscular/fisiologia , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Ratos , Ratos Wistar
17.
Am J Physiol Lung Cell Mol Physiol ; 281(6): L1402-12, 2001 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-11704536

RESUMO

Recent evidence indicates that hypoxia enhances the generation of oxidants. Little is known about the role of free radicals in contractility of the rat diaphragm during hypoxia. We hypothesized that antioxidants improve contractility of the hypoxic rat diaphragm and that xanthine oxidase (XO) is an important source of free radicals in the hypoxic diaphragm. The effects of N-acetylcysteine (NAC; 18 mM), Tiron (10 mM), and the XO inhibitor allopurinol (250 microM) were studied on isometric and isotonic force generation during hypoxia (PO(2) approximately 7 kPa). NAC and Tiron decreased maximal force generation, slowed the shortening velocity, and decreased the power output. Fatigue rate was decreased in the presence of either NAC or Tiron. Allopurinol did not alter the contractility or fatigability of the diaphragm. During hyperoxia (PO(2) approximately 85 kPa), neither NAC nor allopurinol affected the contractility or fatigability of the diaphragm. Thus free radicals play a significant role in diaphragm contractility during hypoxia. Whether antioxidants exert a beneficial or harmful effect on muscle performance depends on the contraction pattern of the muscle. Free radicals generated by XO do not play a role in diaphragm contractility during either hypoxia or hyperoxia.


Assuntos
Diafragma/enzimologia , Hipóxia/metabolismo , Contração Isotônica/fisiologia , Xantina Oxidase/metabolismo , Sal Dissódico do Ácido 1,2-Di-Hidroxibenzeno-3,5 Dissulfônico/farmacologia , Acetilcisteína/farmacologia , Trifosfato de Adenosina/metabolismo , Alopurinol/farmacologia , Animais , Inibidores Enzimáticos/farmacologia , Sequestradores de Radicais Livres/farmacologia , Radicais Livres/metabolismo , Técnicas In Vitro , Indicadores e Reagentes/farmacologia , Contração Isotônica/efeitos dos fármacos , Masculino , Fadiga Muscular/efeitos dos fármacos , Fadiga Muscular/fisiologia , Ratos , Ratos Wistar , Xantina Oxidase/antagonistas & inibidores
18.
J Appl Physiol (1985) ; 91(5): 2117-24, 2001 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-11641352

RESUMO

In the present study, we used real-time confocal microscopy to examine the effects of two nitric oxide (NO) donors on acetylcholine (ACh; 10 microM)- and caffeine (10 mM)-induced intracellular calcium concentration ([Ca2+]i) responses in C2C12 mouse skeletal myotubes. We hypothesized that NO reduces [Ca2+]i in activated skeletal myotubes through oxidation of thiols associated with the sarcoplasmic reticulum Ca2+-release channel. Exposure to diethylamine NONOate (DEA-NO) reversibly increased resting [Ca2+]i level and resulted in a dose-dependent reduction in the amplitude of ACh-induced [Ca2+]i responses (25 +/- 7% reduction with 10 microM DEA-NO and 78 +/- 14% reduction with 100 microM DEA-NO). These effects of DEA-NO were partly reversible after subsequent exposure to dithiothreitol (10 mM). Preexposure to DEA-NO (1, 10, and 50 microM) also reduced the amplitude of the caffeine-induced [Ca2+]i response. Similar data were obtained by using the chemically distinct NO donor S-nitroso-N-acetyl-penicillamine (100 microM). These results indicate that NO reduces sarcoplasmic reticulum Ca2+ release in skeletal myotubes, probably by a modification of hyperreactive thiols present on the ryanodine receptor channel.


Assuntos
Cálcio/metabolismo , Microtúbulos/metabolismo , Músculo Esquelético/metabolismo , Óxido Nítrico/farmacologia , Retículo Sarcoplasmático/metabolismo , Animais , Cafeína/farmacologia , Células Cultivadas , Ditiotreitol/farmacologia , Processamento de Imagem Assistida por Computador , Compostos Macrocíclicos , Camundongos , Microscopia Confocal , Microtúbulos/efeitos dos fármacos , Músculo Esquelético/efeitos dos fármacos , Doadores de Óxido Nítrico/farmacologia , Oxazóis/farmacologia , Oxirredução , Inibidores de Fosfodiesterase/farmacologia , Rianodina/farmacologia , Canal de Liberação de Cálcio do Receptor de Rianodina/efeitos dos fármacos , Canal de Liberação de Cálcio do Receptor de Rianodina/metabolismo , Retículo Sarcoplasmático/efeitos dos fármacos , Compostos de Sulfidrila/metabolismo
19.
J Appl Physiol (1985) ; 91(5): 2233-9, 2001 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-11641366

RESUMO

The effects of the nitric oxide (NO) donor spermine NONOate (Sp-NO, 1.0 mM) on cross-bridge recruitment and cross-bridge cycling kinetics were studied in permeabilized rabbit psoas muscle fibers. Fibers were activated at various Ca2+ concentrations (pCa, negative logarithm of Ca2+ concentration), and the pCa at which force was maximal (pCa 4.0) and approximately 50% of maximal (pCa50 5.6) were determined. Fiber stiffness was determined using 1-kHz sinusoidal length perturbations, and the fraction of cross bridges in the force-generating state was estimated by the ratio of stiffness during maximal (pCa 4.0) and submaximal (pCa 5.6) Ca2+ activation to stiffness during rigor (at pCa 4.0). Cross-bridge cycling kinetics were evaluated by measuring the rate constant for force redevelopment after quick release (by 15% of optimal fiber length, L(o)) and restretch of the fiber to L(o). Exposing fibers to Sp-NO for 10 min reduced force and the fraction of cross bridges in the force-generating state at maximal and submaximal (pCa50) Ca2+ activation. However, the effects of Sp-NO were more pronounced during submaximal Ca2+ activation. Sp-NO also reduced the rate constant for force redevelopment but only during submaximal Ca2+ activation. We conclude that Sp-NO reduces Ca2+ sensitivity by decreasing the number of cross bridges in the strongly bound state and also impairs cross-bridge cycling kinetics during submaximal activation.


Assuntos
Cálcio/fisiologia , Músculo Esquelético/metabolismo , Óxido Nítrico/farmacologia , Algoritmos , Animais , Biotransformação/efeitos dos fármacos , Técnicas In Vitro , Cinética , Contração Muscular/fisiologia , Fibras Musculares Esqueléticas/efeitos dos fármacos , Fibras Musculares Esqueléticas/fisiologia , Músculo Esquelético/citologia , Músculo Esquelético/efeitos dos fármacos , Permeabilidade , Coelhos
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