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| Status |
Public on Sep 21, 2010 |
| Title |
Mechanisms underlying the sparing of masticatory muscle function relative to biceps femoris muscle in an experimental critical illness model |
| Organism |
Sus scrofa |
| Experiment type |
Expression profiling by array
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| Summary |
Background: The aim of this study is to improve our understanding of the mechanisms underlying the sparing of masticatory muscles relative to limb muscles in ICU patients with acute quadriplegic myopathy (AQM) by using a unique porcine ICU model, i.e., 5-day longitudinal experiments where animals are sedated, mechanically ventilated and exposed to factors triggering AQM, such as muscle unloading, endotoxin-induced sepsis, and systemic exposure to CS and NMBA.
Results: An altered expression was notably observed in heat-shock proteins genes, sarcomeric proteins and myostatin genes were noticed. Hence, modifications in heat-shock proteins, sarcomeric proteins and myostatin genes are in sharp contrast to alterations in the limb muscles and it is postulated that elevated heat-shock proteins and decreased sarcomeric protein and myostatin genes play a protective role in the masticatory muscle relative to limb muscle in ICU patients with AQM.
Conclusions: This intervention had no significant effect on masseter muscle fiber size or force-generation capacity. This is in sharp contrast to the dramatic decrease observed in specific force in limb muscle fibers from the same animals. However, significant differences were observed between the craniofacial and the limb muscle with a masseter muscle specific regulation of i) transcriptional and growth factors like RUNX1, FOXO1A, TBX1, PGC1-β and myostatin, ii) several heat shock protein genes like HSP 90, HSP 105/110 and αB-crystallin, iii) a matrix metalloproteinase inhibitor (TIMP2) and iv) oxidative stress responsive elements such as SRXN1 and SOD2. These muscle-type specific differences, the alterations in heat shock protein, sarcomeric protein and myostatin genes are forwarded as important factors underlying the sparing of masticatory muscles compared with limb muscles in critically ill ICU patients with Acute Quadriplegic Myopathy.
Keywords: Treatment, immobilization, muscle function.
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| Overall design |
Five female domestic piglets (Sus scrofa, average body weight 26.9 kg) were used in this study. Five subjects were included for masseter muscle and same four subjects were included for the biceps femoris muscle.
Piglets were immobilized by anesthesia and mechanically ventilated via a tracheotomy for a period of five days. During this study period, the animals were sedated using isoflurane inhalation (Abbott Laboratories, Chicago, Il, USA, 0.8 – 1.3% end-tidal concentration) supplemented by intravenous bolus doses of morphine and ketamine as needed. Core body temperature (blood) was maintained in the range of 38.5 – 40°C by a servo controlled heating pad. The animals received intravenous crystalloid fluid (Ringeracetat) to maintain stable blood pressure and urinary output and a glucose infusion (Rehydrex, Fresenius Kabi, Stockholm, Sweden, 25 mg glucose /mL) in the range of 0.5 – 1.5 mg/kg/minute to decrease the effects of catabolism. Each animal received prophylactic streptomycin 750 mg/d and bensylpenicillin 600 mg/d (Streptocillin Vet, Boeringer-Ingelheim, Hellerup, Denmark). Arterial blood gas analysis as well as electrolytes and blood glucose levels were monitored regularly and kept in the normal range throughout the study period. A neuromuscular blocking agent (NMBA) was administered as a continuous infusion of pancuronium bromide 0.1mg/kg/h (Pavolun; Organon, Boxtel, The Netherlands) for 5days while a corticosteroid (CS) was given as bolus doses of betamethasone 0.1 mg/kg (Betapred; GSK, Slona, Sweden) twice daily for 5days.Endotoxemia was induced by a continuous infusion of Escherichia coli endotoxin, serotype O26:B6 (Sigma Labkemi, Stockholm, Sweden) at 36 µg/kg/h for 1h.
Variables [biceps femoris muscle]:
AQM control: RLPA-Day1_N_CS_S-1PC.CEL(porcine), RLPA-Day1_N_CS_S-2PC.CEL(porcine), RLPA-Day1_N_CS_S-3PC.CEL(porcine), RLPA-Day1_N_CS_S-4PC.CEL(porcine).
AQM treatment: RLPA-Day5_N_CS_S-1PC.CEL(porcine), RLPA-Day5_N_CS_S-2PC.CEL(porcine), RLPA-Day5_N_CS_S-3PC.CEL(porcine), RLPA-Day5_N_CS_S-4PC.CEL(porcine).
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| Contributor(s) |
Aare S, Banduseela VC, Ochala J, Goransson H, Norman H, Radell P, Eriksson LI, Chen Y, Hoffman EP, Larsson L |
| Citation(s) |
22010006 |
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| Submission date |
Sep 20, 2010 |
| Last update date |
May 03, 2013 |
| Contact name |
sudhakar reddy aare |
| Organization name |
uppsala university
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| Department |
neuroscience
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| Lab |
clinical neurophysiology
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| Street address |
Ing 85, 3 tr, Akademiska sjukhuset
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| City |
uppsala |
| ZIP/Postal code |
751 85 |
| Country |
Sweden |
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| Platforms (1) |
| GPL3533 |
[Porcine] Affymetrix Porcine Genome Array |
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| Samples (18)
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| GSM596116 |
Masseter muscle_AQM_Control, rep4 |
| GSM596117 |
Masseter muscle_AQM_Control, rep5 |
| GSM596118 |
Masseter muscle_AQM_Treatment, rep1 |
| GSM596119 |
Masseter muscle_AQM_Treatment, rep2 |
| GSM596120 |
Masseter muscle_AQM_Treatment, rep3 |
| GSM596121 |
Masseter muscle_AQM_Treatment, rep4 |
| GSM596122 |
Masseter muscle_AQM_Treatment, rep5 |
| GSM718994 |
Biceps femoris muscle_AQM_Control_1 |
| GSM718995 |
Biceps femoris muscle_AQM_Control_2 |
| GSM718996 |
Biceps femoris muscle_AQM_Control_3 |
| GSM718997 |
Biceps femoris muscle_AQM_Control_4 |
| GSM718998 |
Biceps femoris muscle_AQM_Treatment_1 |
| GSM718999 |
Biceps femoris muscle_AQM_Treatment_2 |
| GSM719000 |
Biceps femoris muscle_AQM_Treatment_3 |
| GSM719001 |
Biceps femoris muscle_AQM_Treatment_4 |
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| Relations |
| BioProject |
PRJNA132941 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE24239_B.F_up_gene_clusters.txt.gz |
2.6 Kb |
(ftp)(http) |
TXT |
| GSE24239_BF_day5RPLAvsday1CTRL_processed_data.txt.gz |
3.6 Mb |
(ftp)(http) |
TXT |
| GSE24239_RAW.tar |
45.0 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
| Processed data are available on Series record |
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