Hypoxemia-induced modification of troponin I and T in canine diaphragm

Simpson, Jeremy A.; Eyk, Jennifer E. Van; Iscoe, Steve

doi:10.1152/jappl.2000.88.2.753

Cited by 27 publications

(24 citation statements)

References 33 publications

(35 reference statements)

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“…Did proteolysis occur in the tissue or after its release into blood? We previously showed, in severely hypox- emic dogs, that proteolysis of sTnI occurs in the diaphragm, demonstrating that proteolytic fragments form in the muscle cell before release (16 ). This is similar to what happens in the myocardium, where the cTnI undergoes specific and progressive proteolysis (21, 22 ); recombinant human cTnI added to serum undergoes little, if any, proteolysis over 24 h at 37°C (18 ).…”

Section: Discussionmentioning

confidence: 52%

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Fast and Slow Skeletal Troponin I in Serum from Patients with Various Skeletal Muscle Disorders: A Pilot Study

Simpson

Labugger

Collier³

et al. 2005

Clinical Chemistry

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Background: Detection of skeletal muscle injury is hampered by a lack of commercially available assays for serum markers specific for skeletal muscle; serum concentrations of skeletal troponin I (sTnI) could meet this need. Moreover, because sTnI exists in 2 isoforms, slow (ssTnI) and fast (fsTnI), corresponding to slow-and fast-twitch muscles, respectively, it could provide insight into differential injury/recovery of specific fiber types. The purpose of this study was to investigate whether the 2 isoforms of sTnI and their modified forms are present in the blood of patients with various skeletal muscle disorders. Methods: Serial serum samples were obtained from 25 patients with various skeletal muscle injuries. Serum proteins were separated by a modified sodium dodecyl sulfate-polyacrylamide gel electrophoresis protocol followed by Western blotting for sTnI with monoclonal antibodies specific to ssTnI and fsTnI. Results: We observed (a) intact and, in some cases, degraded sTnI products; (b) evidence of posttranslational modifications in addition to proteolysis; and (c) differential detectability of both skeletal isoforms in the same patient. Conclusions: It is possible to monitor both sTnI isoforms; this could lead to the development of new diagnostic assays for skeletal muscle damage.

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Section: Discussionmentioning

confidence: 52%

“…Membranes were blocked overnight at 4°C in 100 mL/L blocking reagent (Roche). Primary antibodies of confirmed isoform specificity were used (16,17 ). These included FI-32 and FI-23 (Spectral Diagnostics) and SI-1 (Hytest), which are specific for fsTnI, and MYNT-S (courtesy of N. Matsumoto), which is specific for ssTnI.…”

Section: Serum Analysismentioning

confidence: 99%

Fast and Slow Skeletal Troponin I in Serum from Patients with Various Skeletal Muscle Disorders: A Pilot Study

Simpson

Labugger

Collier³

et al. 2005

Clinical Chemistry

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“…While we cannot exclude the possibility that other muscles contributed to the released sTnI, severe hypoxemia leading to respiratory arrest in anesthetized dogs induced protein changes only in the diaphragm even though other muscles were activated by the hypoxemia (44). In rabbits, loading injured only the diaphragm, not other respiratory or limb muscles, despite their being exposed to the same asphyxic blood gases (25).…”

Section: Discussionmentioning

confidence: 91%

“…Anti-TnI monoclonal antibodies of confirmed isoform specificity were chosen for WB-DSA: sTnI, FI-32 and FI-23 (fast only, Spectral Diagnostics, Toronto, ON, Canada); MYNT-S (preferential for slow in rat; 31); and 3I-35 (fast, slow, and cardiac; Spectral Diagnostics). Specificity of all antibodies was confirmed by Western blot analysis of cardiac and skeletal tissue from human and rat as described previously (44). To compare release of fast sTnI between loading and sham, blots were scanned at a resolution of 300 dpi, and three-dimensional volume (density) plots were generated; densitometry values of fast sTnI were normalized to levels in control lanes.…”

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confidence: 99%

Cardiorespiratory failure in rat induced by severe inspiratory resistive loading

Simpson¹,

Iscoe²

2007

Journal of Applied Physiology

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Simpson JA, Iscoe S. Cardiorespiratory failure in rat induced by severe inspiratory resistive loading. J Appl Physiol 102: [1556][1557][1558][1559][1560][1561][1562][1563][1564] 2007. First published December 7, 2006; doi:10.1152/japplphysiol.00785.2006.-The mechanisms underlying acute respiratory failure induced by respiratory loads are unclear. We hypothesized that, in contrast to a moderate inspiratory resistive load, a severe one would elicit central respiratory failure (decreased respiratory drive) before diaphragmatic injury and fatigue. We also wished to elucidate the factors that predict endurance time and peak tracheal pressure generation. Anesthetized rats breathed air against a severe load (ϳ75% of the peak tracheal pressure generated during a 30-s occlusion) until pump failure (fall in tracheal pressure to half; mean 38 min). Hypercapnia and hypoxemia developed rapidly (ϳ4 min), coincident with diaphragmatic fatigue (decreased ratio of transdiaphragmatic pressure to peak integrated phrenic activity) and the detection in blood of the fast isoform of skeletal troponin I (muscle injury). At ϳ23 min, respiratory frequency and then blood pressure fell, followed immediately by secondary diaphragmatic fatigue. Blood taken after termination of loading contained cardiac troponin T (myocardial injury). Contrary to our hypothesis, diaphragmatic fatigue and injury occurred early in loading before central failure, evident only as a change in the timing but not the drive component of the central respiratory pattern generator.Stepwise multiple regression analysis selected changes in mean arterial pressure and arterial PCO 2 during loading as the principal contributing factors in load endurance time, and changes in mean arterial pressure as the principal contributing factor in peak tracheal pressure generation. In conclusion, the temporal development of respiratory failure is not stereotyped but depends on load magnitude; moreover respiratory loads induce cardiorespiratory, not just respiratory, failure. diaphragm; fatigue; heart; injury; troponin WHEN THE RESPIRATORY MUSCLES are subjected to contractile demands that exceed their energy supply, respiratory pump failure (inadequate pressure generation) eventually occurs (e.g., 35). Pump failure can result from central failure (inadequate output from the respiratory central pattern generator; sometimes referred to as central fatigue) (50), peripheral fatigue (35) (neurotransmission failure, decreased contractile function; 9), or some combination. Central failure is denoted by a decrease in central neural output despite adequate chemical drive, peripheral fatigue by a reduction in force-generating capacity that is reversible by rest (35), and neurotransmission failure by impaired transmission of the action potential across the neuromuscular junction. All have been implicated in respiratory pump failure, but there is no consensus about either their relative contributions or the sequence in which they occur. Even with similar protocols in healthy human subjects (27,33) o...

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“…There is an increased reliance on anaerobic pathways (5), which, when prolonged, results in an accumulation of metabolic byproducts and ionic disturbances linked with muscle fatigue (6). Excessive production of reactive oxygen species occurs and promotes myosin and actin degradation (7), leading to damage of myofibrillar proteins (8) and reduced functional capacity of skeletal muscles (9). These changes occur at the single fiber level of adult diaphragm (10).…”

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confidence: 99%

Maternal creatine supplementation from mid-pregnancy protects the newborn spiny mouse diaphragm from intrapartum hypoxia-induced damage

et al. 2010

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ABSTRACT:We hypothesized that maternal creatine supplementation from mid-pregnancy would protect the diaphragm of the newborn spiny mouse from the effects of intrapartum hypoxia. Pregnant mice were fed a control or 5% creatine-supplemented diet from mid-gestation. On the day before term, intrapartum hypoxia was induced by isolating the pregnant uterus in a saline bath for 7.5-8 min before releasing and resuscitating the fetuses. Surviving pups were placed with a cross-foster dam, and diaphragm tissue was collected at 24 h postnatal age. Hypoxia caused a significant decrease in the cross-sectional area (ϳ19%) and contractile function (26.6% decrease in maximum Ca 2ϩ -activated force) of diaphragm fibers. The mRNA levels of the muscle mass-regulating genes MuRF1 and myostatin were significantly increased (2-fold). Maternal creatine significantly attenuated hypoxia-induced fiber atrophy, contractile dysfunction, and changes in mRNA levels. This study demonstrates that creatine loading before birth significantly protects the diaphragm from hypoxiainduced damage at birth. (Pediatr Res 68: 393-398, 2010)

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Hypoxemia-induced modification of troponin I and T in canine diaphragm

Cited by 27 publications

References 33 publications

Fast and Slow Skeletal Troponin I in Serum from Patients with Various Skeletal Muscle Disorders: A Pilot Study

Fast and Slow Skeletal Troponin I in Serum from Patients with Various Skeletal Muscle Disorders: A Pilot Study

Cardiorespiratory failure in rat induced by severe inspiratory resistive loading

Maternal creatine supplementation from mid-pregnancy protects the newborn spiny mouse diaphragm from intrapartum hypoxia-induced damage

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