Whole body periodic acceleration in normal and reduced mucociliary clearance of conscious sheep

Abstract

The purpose of this investigation was to ascertain whether nitric oxide (NO) released into the circulation by a noninvasive technology called whole body periodic acceleration (WBPA) could increase mucociliary clearance (MCC). It was based on observations by others that nitric oxide donor drugs increase ciliary beat frequency of nasal epithelium without increasing mucociliary clearance. Tracheal mucous velocity (TMV), a reflection of MCC, was measured in sheep after 1-hour treatment of WBPA and repeated after pretreatment with the NO synthase inhibitor, L-NAME to demonstrated action of NO. Aerosolized human neutrophil elastase (HNE) was administered to sheep to suppress TMV as might occur in cystic fibrosis and other inflammatory lung diseases. WBPA increased TMV to a peak of 136% of baseline 1h after intervention, an effect blocked by L-NAME. HNE reduced TMV to 55% of baseline but slowing was reversed by WBPA, protection lost in the presence of L-NAME. NO released into the circulation from eNOS by WBPA can acutely access airway epithelium for improving MCC slowed in cystic fibrosis and other inflammatory lung diseases as a means of enhancing host defense against pathogens.

Cardioprotective Effect of Whole Body Periodic Acceleration in Dystrophic Phenotype mdx Rodent

“…This conclusion is supported by the fact that 3-month treatment with WBPA slows the development of cardiomyopathy in mdx 15-month old mice by normalizing intracellular ion dyshomeostasis, reducing intracellular ROS production and cell injury, which enhances contractile function and increases cell viability. WBPA as a therapeutic approach to treat DMD has some advantages compared with current available treatments; (1) WBPA is not a pharmacological approach, therefore no toxicology and preclinical pharmacokinetic studies are required before its use in patients; (2) is easily translated from being a research platform to patients; (3) It is non-invasive, non-stressful and able to be used even in those with physical limitations; (4) No side effects have been observed in experimental models of DMD and other diseases ( Adams et al, 2014 ; Altamirano et al, 2014 ; Lopez et al, 2017 , 2018 ; Sabater et al, 2019 ) as well as in various human clinical trials on non-DMD patients ( Sackner et al, 2004 ; Kohler et al, 2007 ; Rokutanda et al, 2011 ; Sakaguchi et al, 2012 ; Serravite et al, 2014 ; Adams et al, 2020 ); (5) WBPA not only protects and improves function in cardiac cells but also has a similar effect in skeletal muscle ( Altamirano et al, 2014 ) and in neurons ( Lopez et al, 2018 ) all of which are affected in DMD.…”

Effect of airway clearance therapies on mucociliary clearance in adults with cystic fibrosis: A randomized controlled trial

“…cyclase to increase ciliary beat frequency, and thus may promote or reflect increased MCC [27,28]. Indeed, this relationship was demonstrated in sheep, and whole-body vibration was implicated to accelerate MCC via increased NO release [29]. We anticipated that with stimulated MCC via ACT, FeNO would increase, but instead found a small, but opposite, effect.…”