Transcranial Doppler (TCD) determined cerebral blood flow velocity and laser Doppler flowmetry (LDF) measured cortical perfusion were simultaneously assessed during hypotensive haemorrhage in 15 anaesthetized rabbits. Systolic (Fsys), diastolic (Fdia) and mean (Fmean) blood flow velocities were recorded into the intracranial internal carotid (ICA) and basilar artery (BA). Resistance (RI = Fsys-Fdia/Fsys) and pulsatility (PI = Fsys-Fdia/Fmean) indices were calculated. Step decreases of 10 mmHg of mean arterial pressure (MAP) from 80 to less than 30 mmHg provoked a fall of LDF signal below 50 mmHg. Blood velocities decreased into BA below 40 mmHg, and below 50 mmHg into ICA indicating regional differences in cerebral autoregulation. Cortical resistances (resLDF = MAP/LDF) fell below 60 mmHg whereas RI and PI increased when MAP decreased into BA below 40 mmHg and ICA below 50 mmHg. A weak correlation was found between Fmean and LDF (BA: r = 0.55, P < 0.01 and ICA = 0.46, P < 0.01). Both RI and PI were poorly correlated to resLDF into BA (RI-resLDF: r = -0.39, P < 0.01; PI-resLDF: r = -0.39, P < 0.01) and ICA (RI-resLDF: r = -0.18, ns; PI-resLDF: r = -0.22, ns). Pulse pressure (systolic-diastolic pressure) correlated with RI (ICA: r = -0.62, P < 0.001; BA: r = -0.61, P < 0.001) and PI (ICA: r = -0.61, P < 0.001; BA: r = -0.62, P < 0.001). In conclusion, during haemorrhagic shock, TCD correlates with LDF and indicates regional differences in autoregulatory settings. However, Doppler indices do not reflect the changes in cerebral resistances because they are influenced by the changes in pulsatile pressure.

BackgroundCongenital nemaline myopathies are rare pathologies characterised by muscle weakness and rod-shaped inclusions in the muscle fibres.MethodsUsing next-generation sequencing, we identified three patients with pathogenic variants in the Troponin T type 1 (TNNT1) gene, coding for the troponin T (TNT) skeletal muscle isoform.ResultsThe clinical phenotype was similar in all patients, associating hypotonia, orthopaedic deformities and progressive chronic respiratory failure, leading to early death. The anatomopathological phenotype was characterised by a disproportion in the muscle fibre size, endomysial fibrosis and nemaline rods. Molecular analyses of TNNT1 revealed a homozygous deletion of exons 8 and 9 in patient 1; a heterozygous nonsense mutation in exon 9 and retention of part of intron 4 in muscle transcripts in patient 2; and a homozygous, very early nonsense mutation in patient 3.Western blot analyses confirmed the absence of the TNT protein resulting from these mutations.DiscussionThe clinical and anatomopathological presentations of our patients reinforce the homogeneous character of the phenotype associated with recessive TNNT1 mutations. Previous studies revealed an impact of recessive variants on the tropomyosin-binding affinity of TNT. We report in our patients a complete loss of TNT protein due to open reading frame disruption or to post-translational degradation of TNT.

No abstract

No abstract

No abstract