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1.
Am J Physiol Lung Cell Mol Physiol ; 325(5): L638-L646, 2023 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-37724348

RESUMO

This study aimed to develop a three-dimensional (3-D) method for assessing ventilation/perfusion (V/Q̇) ratios in a pig model of hemodynamic perturbations using electrical impedance tomography (EIT). To evaluate the physiological coherence of changes in EIT-derived V/Q̇ ratios, global EIT-derived V/Q̇ mismatches were compared with global gold standards. The study found regional heterogeneity in the distribution of V/Q̇ ratios in both the ventrodorsal and craniocaudal directions. Although global EIT-derived indices of V/Q̇ mismatch consistently underestimated both low and high V/Q̇ mismatch compared with global gold standards, the direction of the change was similar. We made the software available at no cost for other researchers to use. Future studies should compare regional V/Q̇ ratios determined by our method against other regional, high-resolution methods.NEW & NOTEWORTHY In this study, we introduce a novel 3-D method for assessing ventilation-perfusion (V/Q̇) ratios using electrical impedance tomography (EIT). Heterogeneity in V/Q̇ distribution showcases the significant potential for enhanced understanding of pulmonary conditions. This work signifies a substantial step forward in the application of EIT for monitoring and managing lung diseases.

2.
Genes (Basel) ; 14(5)2023 04 27.
Artigo em Inglês | MEDLINE | ID: mdl-37239348

RESUMO

Sudden cardiac death in the young (SCDY) is a devastating event that often has an underlying genetic basis. Manchester Terrier dogs offer a naturally occurring model of SCDY, with sudden death of puppies as the manifestation of an inherited dilated cardiomyopathy (DCM). We performed a genome-wide association study for SCDY/DCM in Manchester Terrier dogs and identified a susceptibility locus harboring the cardiac ATP-sensitive potassium channel gene ABCC9. Sanger sequencing revealed an ABCC9 p.R1186Q variant present in a homozygous state in all SCDY/DCM-affected dogs (n = 26). None of the controls genotyped (n = 398) were homozygous for the variant, but 69 were heterozygous carriers, consistent with autosomal recessive inheritance with complete penetrance (p = 4 × 10-42 for the association of homozygosity for ABCC9 p.R1186Q with SCDY/DCM). This variant exists at low frequency in human populations (rs776973456) with clinical significance previously deemed uncertain. The results of this study further the evidence that ABCC9 is a susceptibility gene for SCDY/DCM and highlight the potential application of dog models to predict the clinical significance of human variants.


Assuntos
Cardiomiopatia Dilatada , Morte Súbita Cardíaca , Doenças do Cão , Receptores de Sulfonilureias , Animais , Cães , Cardiomiopatia Dilatada/genética , Cardiomiopatia Dilatada/veterinária , Morte Súbita Cardíaca/etiologia , Morte Súbita Cardíaca/veterinária , Estudo de Associação Genômica Ampla , Genótipo , Mutação de Sentido Incorreto , Receptores de Sulfonilureias/genética , Doenças do Cão/genética
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