Biomedical subjects

Karen Maes

Publications and source records attributed to Karen Maes.

4 recordsLinked to original sources

PubMed2006

Rocuronium exacerbates mechanical ventilation-induced diaphragm dysfunction in rats.

OBJECTIVE: Nondepolarizing neuromuscular blocking agents are commonly used in the intensive care setting, but they have occasionally been associated with development of myopathy. In addition, diaphragmatic atrophy and a reduction in diaphragmatic force were reported after short-term controlled mechanical ventilation in animal models. We hypothesized that infusion of rocuronium, an aminosteroidal neuromuscular blocking agent, during 24 hrs of controlled mechanical ventilation would further alter diaphragm function and would enhance activation of the ubiquitin- proteasome pathway. DESIGN: Randomized, controlled experiment. SETTING: Basic animal science laboratory. SUBJECTS: Male Wistar rats, 14 wks old. INTERVENTIONS: Rats were divided into four groups: a control group, a group of anesthetized rats breathing spontaneously for 24 hrs, and two groups submitted to mechanical ventilation for 24 hrs, receiving a continuous infusion of either 0.9% NaCl or rocuronium. MEASUREMENTS AND MAIN RESULTS: In vitro diaphragm force was decreased more significantly after 24 hrs of mechanical ventilation combined with rocuronium infusion than after mechanical ventilation alone (e.g., tetanic force, -27%; p < .001 vs. mechanical ventilation). Similarly, the decrease in diaphragm type IIx/b fiber dimensions was more pronounced after mechanical ventilation with rocuronium treatment than with saline treatment (-38% and -29%, respectively; p < .001 vs. control). Diaphragm hydroperoxide levels increased similarly in both mechanically ventilated groups. Diaphragm muscle RING-finger protein-1 (MURF-1) messenger RNA expression, an E3 ligase of the ubiquitin-proteasome pathway, increased after mechanical ventilation (+212%, p < .001 vs. control) and increased further with combination of rocuronium (+320%, p < .001 vs. control). Significant correlations were found between expression of MURF-1 messenger RNA, diaphragm force, and type IIx/b fiber dimensions. CONCLUSIONS: Infusion of rocuronium during controlled mechanical ventilation leads to further deterioration of diaphragm function, additional atrophy of type IIx/b fibers, and an increase in MURF-1 messenger RNA in the diaphragm, which suggests an activation of the ubiquitin-proteasome pathway. These findings could be important with regard to weaning failure in patients receiving this drug for prolonged periods in the intensive care unit setting.

Androstanols↗

PubMed2005

Interleukin-6 causes myocardial failure and skeletal muscle atrophy in rats.

BACKGROUND: The impact of interleukin (IL)-6 on skeletal muscle function remains the subject of controversy. METHODS AND RESULTS: The effects of 7-day subcutaneous administration of recombinant human IL-6 were examined at 3 doses, 50, 100, or 250 microg x kg(-1) x d(-1), in rats. Skeletal muscle mass decreased dose-dependently (with increasing dose: in the diaphragm, -10%, P=NS; -15%, P=0.0561; and -15% P<0.05; and in the gastrocnemius, -9%, P=NS; -9%, P=NS; and -18%, P<0.005) because of decreases in cross-sectional area of all fiber types without alterations in diaphragm contractile properties. Cardiovascular variables showed a dose-dependent heart dilatation (for end-diastolic volume: control, 78 microL; moderate dose, 123 microL; and high dose, 137 microL, P<0.001), reduced end-systolic pressure (control, 113 mm Hg; moderate dose, 87 mm Hg; and high dose, 90 mm Hg; P=0.037), and decreased myocardial contractility (for preload recruitable stroke work: control, 79 mm Hg; moderate dose, 67 mm Hg; and high dose, 48 mm Hg; P<0.001). Lung edema was confirmed by an increased wet-to-dry ratio (control, 4.2; moderate dose, 4.6; and high dose, 4.5; P<0.001) and microscopy findings. These cardiovascular alterations led to decreases in organ blood flow, particularly in the diaphragm (control, 0.56 mL x min(-1) x g(-1); moderate dose, 0.21 mL x min(-1) x g(-1); and high dose, 0.23 mL x min(-1) x g(-1); P=0.037). In vitro recombinant human IL-6 administration did not cause any alterations in diaphragm force or endurance capacity. CONCLUSIONS: IL-6 clearly caused ventilatory and peripheral skeletal muscle atrophy, even after short-term administration. Blood flow redistribution, resulting from the myocardial failure induced by IL-6, was likely responsible for this muscle atrophy, because IL-6 did not exert any direct effect on the diaphragm.

Animals↗

PubMed2005

Intermittent spontaneous breathing protects the rat diaphragm from mechanical ventilation effects.

OBJECTIVE: Short-term mechanical ventilation has been proven to reduce diaphragm force and fiber dimensions. We hypothesized that intermittent spontaneous breathing during the course of mechanical ventilation would minimize the effects of mechanical ventilation on diaphragm force and expression levels of transcription factors (MyoD and myogenin). DESIGN: Randomized, controlled experiment. SETTING: Animal basic science laboratory. SUBJECTS: Male Wistar rats, weighing 350-500 g. INTERVENTIONS: Anesthetized and tracheotomized rats were submitted to either 24 hrs of spontaneous breathing (SB, n = 5), 24 hrs of continuous controlled mechanical ventilation (CMV, n = 7), or controlled mechanical ventilation with intermittent spontaneous breathing: 60 mins every 5 hrs of mechanical ventilation repeated four times (ISB60, n = 8) or 5 mins every 5 hrs 55 mins of mechanical ventilation repeated four times (SB5, n = 9). They were compared with control animals free from intervention (C, n = 5). MEASUREMENTS AND MAIN RESULTS: The profile of the diaphragm force-frequency curve of the controls and SB group was significantly different from that of the ISB and CMV groups; especially, the mean asymptotic force was less in the ISB and CMV compared with controls and SB. CMV resulted in a significant decrease in the diaphragm type I (-26%, p < .05 vs. C) and type IIx/b (-39%, p < .005 vs. C and SB) cross-sectional area, whereas this was not observed in the ISB groups. Diaphragm MyoD protein expression was significantly decreased after ISB60 (-35%, p < .0001 vs. C and SB) and even more after CMV (-73%, p < .0001 vs. others). The same pattern was observed with myogenin protein levels. Positive relationships between diaphragm MyoD and myogenin protein levels and diaphragm force were observed. CONCLUSIONS: The data demonstrated that intermittent spontaneous breathing during the course of mechanical ventilation may minimize the deleterious effect of controlled mechanical ventilation on diaphragm force, fiber dimensions, and expression of transcription factors.

Animals↗

PubMed2004

The rat cytomegalovirus homologue of parvoviral rep genes, r127, encodes a nuclear protein with single- and double-stranded DNA-binding activity that is dispensable for virus replication.

An intriguing feature of the rat cytomegalovirus (RCMV) genome is open reading frame (ORF) r127, which shows similarity to the rep genes of parvoviruses as well as the U94 genes of human herpesvirus type 6A (HHV-6A) and 6B (HHV-6B). Counterparts of these genes have not been found in other herpesviruses. Here, it is shown that the r127 gene is transcribed during the early and late phases of virus replication in vitro as an unspliced 1.1 kb transcript containing the complete r127 ORF. Transcripts of r127 were also detected in various organs of RCMV-infected rats at 1 week post-infection (p.i.), but only in the salivary gland at 4 months p.i. Using rabbit polyclonal antibodies raised against the r127-encoded protein (pr127), pr127 was found to be expressed as early as 12 h p.i. within the nuclei of RCMV-infected cells in vitro. Expression of pr127 was also observed within the nuclei of cells in various organs of RCMV-infected rats at 3 weeks p.i. Moreover, pr127 was demonstrated to bind single- as well as double-stranded DNA. Finally, an RCMV r127 deletion mutant (RCMVDeltar127) was generated, in which the r127 ORF was disrupted. This deletion mutant, however, was shown to replicate with a similar efficiency as wild-type RCMV (wt RCMV), both in vitro and in vivo. Taken together, it is concluded that the RCMV r127 gene encodes a nuclear protein with single- and double-stranded DNA-binding activity that is dispensable for virus replication, not only in vitro, but also during the acute phase of infection in vivo.

Amino Acid Sequence↗