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Robinder G Khemani - One of the best experts on this subject based on the ideXlab platform.
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neurally adjusted ventilatory assist mitigates ventilator induced Diaphragm Injury in rabbits
Respiratory Research, 2019Co-Authors: Tatsutoshi Shimatani, Nobuaki Shime, Tomohiko Nakamura, Shinichiro Ohshimo, Justin Hotz, Robinder G KhemaniAbstract:Ventilator-induced Diaphragmatic dysfunction is a serious complication associated with higher ICU mortality, prolonged mechanical ventilation, and unsuccessful withdrawal from mechanical ventilation. Although neurally adjusted ventilatory assist (NAVA) could be associated with lower patient-ventilator asynchrony compared with conventional ventilation, its effects on Diaphragmatic dysfunction have not yet been well elucidated. Twenty Japanese white rabbits were randomly divided into four groups, (1) no ventilation, (2) controlled mechanical ventilation (CMV) with continuous neuromuscular blockade, (3) NAVA, and (4) pressure support ventilation (PSV). Ventilated rabbits had lung Injury induced, and mechanical ventilation was continued for 12 h. Respiratory waveforms were continuously recorded, and the asynchronous events measured. Subsequently, the animals were euthanized, and Diaphragm and lung tissue were removed, and stained with Hematoxylin-Eosin to evaluate the extent of lung Injury. The myofiber cross-sectional area of the Diaphragm was evaluated under the adenosine triphosphatase staining, sarcomere disruptions by electron microscopy, apoptotic cell numbers by the TUNEL method, and quantitative analysis of Caspase-3 mRNA expression by real-time polymerase chain reaction. Physiological index, respiratory parameters, and histologic lung Injury were not significantly different among the CMV, NAVA, and PSV. NAVA had lower asynchronous events than PSV (median [interquartile range], NAVA, 1.1 [0–2.2], PSV, 6.8 [3.8–10.0], p = 0.023). No differences were seen in the cross-sectional areas of myofibers between NAVA and PSV, but those of Type 1, 2A, and 2B fibers were lower in CMV compared with NAVA. The area fraction of sarcomere disruptions was lower in NAVA than PSV (NAVA vs PSV; 1.6 [1.5–2.8] vs 3.6 [2.7–4.3], p < 0.001). The proportion of apoptotic cells was lower in NAVA group than in PSV (NAVA vs PSV; 3.5 [2.5–6.4] vs 12.1 [8.9–18.1], p < 0.001). There was a tendency in the decreased expression levels of Caspase-3 mRNA in NAVA groups. Asynchrony Index was a mediator in the relationship between NAVA and sarcomere disruptions. Preservation of spontaneous breathing using either PSV or NAVA can preserve the cross sectional area of the Diaphragm to prevent atrophy. However, NAVA may be superior to PSV in preventing sarcomere Injury and apoptosis of myofibrotic cells of the Diaphragm, and this effect may be mediated by patient-ventilator asynchrony.
W D Reid - One of the best experts on this subject based on the ideXlab platform.
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increased Injury and intramuscular collagen of the Diaphragm in copd autopsy observations
European Respiratory Journal, 2006Co-Authors: Alex Scott, Jeremy Road, X Wang, W D ReidAbstract:Evidence for Diaphragm Injury in people with chronic obstructive pulmonary disease (COPD) has been reported, although the extent of Injury and collagen accumulation post mortem have not previously been examined. In addition, it is not known whether the amount of Injury and collagen are different in key regions of the Diaphragm. The cross-sectional area of collagen and the percentage of abnormal myofibres in the post mortem Diaphragm and psoas major were determined by computer-assisted image analysis of stained cross-sections of the Diaphragm for collagen with picrosirius red and with haematoxylin and eosin for morphology. In the midcostal Diaphragm of six subjects with COPD and six subjects with no significant respiratory disease, the COPD Diaphragm displayed a greater cross-sectional area of collagen and percentage of abnormal myofibres (collagen: 24.2+/-1.0 versus 18.6+/-1.1%; Injury: 28.4+/-7.2 versus 12.0+/-1.3%). In 18 patients with various respiratory conditions, the midcostal Diaphragm displayed more collagen and abnormal myofibres than the crural Diaphragm, while both costal and crural Diaphragms displaying more collagen and abnormal myofibres than psoas major. This study reveals extensive Injury and collagen accumulation in the chronic obstructive pulmonary diseased Diaphragm, and reveals a regional pattern of Injury and intramuscular collagen which may correspond to variations in Diaphragm loading.
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time course of Diaphragm Injury and calpain activity during resistive loading
American Journal of Respiratory and Critical Care Medicine, 2000Co-Authors: W D Reid, Angelo N BelcastroAbstract:The purpose of this study was to determine the time course of arterial blood gas (ABG) deterioration, increased calpain activity, and Diaphragm Injury during 4 d of resistive loading. Adult Sprague– Dawley rats were divided into control (C) animals and groups that were tracheally banded (TB) for 1 d (TB1), 2 d (TB2), 3 d (TB3), and 4 d (TB4). In TB rats, the carotid artery was cannulated and the trachea was banded during anesthesia. TB groups (TB1, TB2, TB3, and TB4) had a 67% smaller internal cross-sectional area of the trachea than did C animals. ABG samples from awake rats showed a decreased arterial oxygen tension (PaO2 ) and a respiratory acidosis in the TB1, TB2, and TB3 groups. Calpain activity was higher in the Diaphragm of TB than of C rats; calpainlike activities in soluble fractions of Diaphragm tissue were greater in all TB groups than in C rats, whereas those in bound fractions were greater in the TB2 and TB3 groups. Point counting of hematoxylin and eosin-stained cross-sections showed that t...
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chronic resistive loading induces Diaphragm Injury and ventilatory failure in the hamster
Respiration Physiology, 1999Co-Authors: W D Reid, Angelo N BelcastroAbstract:Abstract The purpose of this study was to examine the effects of tracheal banding for 30 days on arterial blood gases, and Diaphragm structure and function. Hamsters were tracheal banded (TB) or underwent a sham procedure (C) ( n =16 and 18, respectively). After 30 days, arterial blood gases from awake TB hamsters showed hypoxemia and a respiratory acidosis. Histochemical analysis of Diaphragm cross-sections showed a five-fold greater area fraction of abnormal muscle; a greater variation in fiber size; and a 3% higher proportion of type 1 fibers in TB than C hamsters. In vitro physiologic studies of costal strips from TB hamsters showed lower stress (45–70% over 10–100Hz) than C values. Maximal esophageal pressure during occlusion was 45% higher and normalized Diaphragm mass was 10% higher in TB hamsters than C hamsters. We conclude that the lower stress in vitro was attributable, at least in part, to Diaphragm Injury. Hypercapnea was present in spite of the higher Diaphragm mass and maximal esophageal pressures in banded hamsters.
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Delayed Diaphragm Injury and Diaphragm force production.
American journal of respiratory and critical care medicine, 1998Co-Authors: T X Jiang, W D Reid, J D RoadAbstract:The present study was designed to examine the effect of delayed Diaphragm Injury produced by inspiratory resistive loading (IRL) on Diaphragm force production. On Day 1, three groups of anesthetized and intubated NZW rabbits (n = 7 in each group) were subjected to moderate IRL (Pao approximately 30 cm H2O), high IRL (Pao approximately 45 cm H2O), or no load for 1.5 h. On Day 3, the baseline twitch transDiaphragmatic pressure (Pdi) and Pdi at 10 to 80 Hz were measured during bilateral phrenic stimulation and these measurements were repeated after another IRL (high level) in all three groups. Diaphragm Injury was assessed by the point-counting technique. Marked Diaphragm Injury was observed in the high-IRL group (p < 0.01), but no significant Diaphragm Injury was observed in the moderate-IRL or control groups. The baseline twitch Pdi was maintained in both IRL groups, whereas the baseline Pdi-frequency values in the high-IRL group were significantly reduced at most frequencies (p < 0.05). The decreases in twitch and Pdi at different frequencies were more pronounced after the IRL on Day 3 in the high-IRL group compared with controls. Moderate IRL did not decrease Diaphragm force either before or after the high IRL on Day 3. We conclude that the Diaphragm Injury induced by high IRL has a significant impact on Diaphragm force production and the attendant force loss produced by IRL is dependent on the intensity of inspiratory loading.
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load dependence of secondary Diaphragm inflammation and Injury after acute inspiratory loading
American Journal of Respiratory and Critical Care Medicine, 1998Co-Authors: T X Jiang, W D Reid, A Belcastro, J D RoadAbstract:Chronic or prolonged low-intensity loading of the inspiratory muscles has recently been shown to produce Diaphragm Injury. The present study was designed to examine whether an acute episode of inspiratory resistive loading (IRL) could produce secondary Diaphragm inflammation and Injury. On Day 1, three groups of anesthetized and intubated New Zealand White rabbits were subjected to moderate IRL (Pao of approximately 30 cm H2O), high IRL (Pao of approximately 45 cm H2O), or no load for 1.5 h. On Day 3, costal and crural Diaphragms, parasternals, and gastrocnemius muscles were taken to assess Injury by point counting. Normal muscle, abnormal and inflamed muscle, and connective tissue on hematoxylin and eosin-stained cross-sections were expressed as percentage of the total points for that cross-section. For the costal Diaphragm, both the abnormal muscle (7.3 +/- 0.6% versus 1.1 +/- 0.2%; p < 0.001) and connective tissue (8.0 +/- 0.6% versus 5.7 +/- 0.2%; p < 0.01) in the high IRL group were higher than control, whereas in the moderate IRL group they were not significantly different from control. Total calpain-like activity was increased in the moderate IRL group but not in the high IRL group. Injury was observed in the parasternal muscles but to a lesser extent. No Injury was observed in the gastrocnemius muscle. We conclude that secondary Diaphragm Injury occurs after acute IRL but only when the IRL exceeds the fatigue threshold.
Angelo N Belcastro - One of the best experts on this subject based on the ideXlab platform.
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time course of Diaphragm Injury and calpain activity during resistive loading
American Journal of Respiratory and Critical Care Medicine, 2000Co-Authors: W D Reid, Angelo N BelcastroAbstract:The purpose of this study was to determine the time course of arterial blood gas (ABG) deterioration, increased calpain activity, and Diaphragm Injury during 4 d of resistive loading. Adult Sprague– Dawley rats were divided into control (C) animals and groups that were tracheally banded (TB) for 1 d (TB1), 2 d (TB2), 3 d (TB3), and 4 d (TB4). In TB rats, the carotid artery was cannulated and the trachea was banded during anesthesia. TB groups (TB1, TB2, TB3, and TB4) had a 67% smaller internal cross-sectional area of the trachea than did C animals. ABG samples from awake rats showed a decreased arterial oxygen tension (PaO2 ) and a respiratory acidosis in the TB1, TB2, and TB3 groups. Calpain activity was higher in the Diaphragm of TB than of C rats; calpainlike activities in soluble fractions of Diaphragm tissue were greater in all TB groups than in C rats, whereas those in bound fractions were greater in the TB2 and TB3 groups. Point counting of hematoxylin and eosin-stained cross-sections showed that t...
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chronic resistive loading induces Diaphragm Injury and ventilatory failure in the hamster
Respiration Physiology, 1999Co-Authors: W D Reid, Angelo N BelcastroAbstract:Abstract The purpose of this study was to examine the effects of tracheal banding for 30 days on arterial blood gases, and Diaphragm structure and function. Hamsters were tracheal banded (TB) or underwent a sham procedure (C) ( n =16 and 18, respectively). After 30 days, arterial blood gases from awake TB hamsters showed hypoxemia and a respiratory acidosis. Histochemical analysis of Diaphragm cross-sections showed a five-fold greater area fraction of abnormal muscle; a greater variation in fiber size; and a 3% higher proportion of type 1 fibers in TB than C hamsters. In vitro physiologic studies of costal strips from TB hamsters showed lower stress (45–70% over 10–100Hz) than C values. Maximal esophageal pressure during occlusion was 45% higher and normalized Diaphragm mass was 10% higher in TB hamsters than C hamsters. We conclude that the lower stress in vitro was attributable, at least in part, to Diaphragm Injury. Hypercapnea was present in spite of the higher Diaphragm mass and maximal esophageal pressures in banded hamsters.
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Diaphragm Injury and myofibrillar structure induced by resistive loading
Journal of Applied Physiology, 1994Co-Authors: W D Reid, J Huang, S Bryson, D C Walker, Angelo N BelcastroAbstract:The purpose of this study was to determine whether ventilatory failure is associated with muscle fiber damage and myofibrillar protein alterations. Ventilatory failure was induced by tightening a polyvinyl band around the trachea of hamsters (TB; n = 14) for 6 days, which resulted in severe respiratory acidosis (PCO2: 97.9 +/- 29.6 vs. 51.6 +/- 19.6 Torr; pH: 7.16 vs. 7.35), hypoxemia (PO2: 42.8 +/- 16.8 vs. 65.9 +/- 25.8 Torr), and increased pulmonary resistance (1.89 +/- 1.61 vs. 0.29 +/- 0.27 cmH2O.ml-1 x min; P < 0.05). The point-counting technique of hematoxylin- and eosin-stained cross sections showed a higher area fraction of abnormal muscle and inflammatory cells in the costal [0.133 +/- (SE) 0.33 vs. 0.040 +/- 0.010] and crural regions (0.069 +/- 0.020 vs. 0.012 +/- 0.003) of the Diaphragm in TB hamsters than in control hamsters. Electron micrographs revealed sarcomeric disruption and Z band streaming in the Diaphragm of TB hamsters. Myofibrillar changes of the Diaphragm associated with ventilatory failure were quantitative (i.e., a lower yield of purified myofibrils) but not qualitative (similar sodium dodecyl sulfate-polyacrylamide gel electrophoresis protein profiles); however, sulfhydryl group reactivities were reduced (P < 0.05). Proteolysis of purified myofibrils from the Diaphragm digested with calpain showed faster degradation rates for tropomyosin and alpha-actinin but not for all proteins for the TB animals. Ventilatory failure induced by resistive loading was associated with Diaphragm Injury; some of this Injury was linked to changes in myofibrillar complexes, specifically their susceptibility to calpain-mediated degradation.
Marcelo Gama De Abreu - One of the best experts on this subject based on the ideXlab platform.
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static and dynamic transpulmonary driving pressures affect lung and Diaphragm Injury during pressure controlled versus pressure support ventilation in experimental mild lung Injury in rats
Anesthesiology, 2020Co-Authors: Eliete F Pinto, Raquel S Santos, Mariana A Antunes, Ligia De A Maia, Gisele A Padilha, Joana Machado, Anna C F Carvalho, Marcos V S Fernandes, Vera Luiza Capelozzi, Marcelo Gama De AbreuAbstract:Background:Pressure-support ventilation may worsen lung damage due to increased dynamic transpulmonary driving pressure. The authors hypothesized that, at the same tidal volume (VT) and dynamic transpulmonary driving pressure, pressure-support and pressure-controlled ventilation would yield comparab
Kejing Ying - One of the best experts on this subject based on the ideXlab platform.
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high level pressure support ventilation attenuates control mechanical ventilator induced Diaphragm Injury in healthy rabbits
European Respiratory Journal, 2014Co-Authors: Liying Chen, Kejing YingAbstract:Background: The aim of this study is to confirm HL-PSV can induce damage to the animal9s Diaphragm compared to other mechanical ventilation modes at same level support. Methods: Twenty New Zealand Rabbits were randomly assigned to four groups (n=5 each group).no mechanical ventilation (CON); Control mode ventilation (CMV); Assist/control ventilation (A/C); High-level pressure support ventilation (HL-PSV) mode. Diaphragm electric activity (EAdi) was analyzed. Impact of Diaphragm protease activation and muscle fiber Injury were observed. Results: (1) Compared to CMV and A/C group, the level of Fc decreasing in HL-PSV is the lowest (P (2) Compared to CMV and A/C group, HL-PSV group attenuated elevated active caspase-3 protein activation (p . (3) PSV mode attenuated the Diaphragm mitochondrial Injury, according to the structure. Conclusions: HL-PSV mode for patients with ventilation support can prevent Diaphragm Injury and dysfunction.