The novel Mechanical Ventilator Milano for the COVID-19 pandemic.

This paper presents the Mechanical Ventilator Milano (MVM), a novel intensive therapy mechanical ventilator designed for rapid, large-scale, low-cost production for the COVID-19 pandemic. Free of moving mechanical parts and requiring only a source of compressed oxygen and medical air to operate, the MVM is designed to support the long-term invasive ventilation often required for COVID-19 patients and operates in pressure-regulated ventilation modes, which minimize the risk of furthering lung trauma. The MVM was extensively tested against ISO standards in the laboratory using a breathing simulator, with good agreement between input and measured breathing parameters and performing correctly in response to fault conditions and stability tests. The MVM has obtained Emergency Use Authorization by U.S. Food and Drug Administration (FDA) for use in healthcare settings during the COVID-19 pandemic and Health Canada Medical Device Authorization for Importation or Sale, under Interim Order for Use in Relation to COVID-19. Following these certifications, mass production is ongoing and distribution is under way in several countries. The MVM was designed, tested, prepared for certification, and mass produced in the space of a few months by a unique collaboration of respiratory healthcare professionals and experimental physicists, working with industrial partners, and is an excellent ventilator candidate for this pandemic anywhere in the world.

Effect of glutaraldehyde based cross-linking on the viscoelasticity of mitral valve basal chordae tendineae.

BACKGROUND: Mitral valve failure can require repair or replacement. Replacement bioprosthetic valves are treated with glutaraldehyde prior to implantation. The aim of this study was to determine the changes in mechanical properties following glutaraldehyde fixation of mitral valve chordae. METHODS: To investigate the impact of glutaraldehyde on mitral valve chordae, 24 basal chordae were dissected from four porcine hearts. Anterior and posterior basal (including strut) chordae were used. All 24 chordae were subjected to a sinusoidally varying load (mean level 2N, dynamic amplitude 2N) over a frequency range of 0.5-10 Hz before and after glutaraldehyde treatment. RESULTS: The storage and loss modulus of all chordal types decreased following glutaraldehyde fixation. The storage modulus ranged from: 108 to 119 MPa before fixation and 67.3-87.4 MPa following fixation for basal chordae; 52.3-58.4 MPa before fixation and 47.9-53.5 MPa following fixation for strut chordae. Similarly, the loss modulus ranged from: 5.47 to 6.25 MPa before fixation and 3.63-4.94 MPa following fixation for basal chordae; 2.60-2.97 MPa before fixation and 2.31-2.93 MPa following fixation for strut chordae. CONCLUSION: The viscoelastic properties of mitral valve chordae are affected by glutaraldehyde fixation; in particular, the reduction in storage moduli decreased with an increase in chordal diameter.

Adenosine-evoked Na+ transport in human airway epithelial cells.

BACKGROUND AND PURPOSE: Absorptive epithelia express apical receptors that allow nucleotides to inhibit Na(+) transport but ATP unexpectedly stimulated this process in an absorptive cell line derived from human bronchiolar epithelium (H441 cells) whilst UTP consistently caused inhibition. We have therefore examined the pharmacological basis of this anomalous effect of ATP. EXPERIMENTAL APPROACH: H441 cells were grown on membranes and the short circuit current (I(SC)) measured in Ussing chambers. In some experiments, [Ca(2+)](i) was measured fluorimetrically using Fura -2. mRNAs for adenosine receptors were determined by the polymerase chain reaction (PCR). KEY RESULTS: Cross desensitization experiments showed that the inhibitory response to UTP was abolished by prior exposure to ATP whilst the stimulatory response to ATP persisted in UTP-pre-stimulated cells. Apical adenosine evoked an increase in I(SC) and this response resembled the stimulatory component of the response to ATP, and could be mimicked by adenosine receptor agonists. Pre-stimulation with adenosine abolished the stimulatory component of the response to ATP. mRNA encoding A(1), A(2A) and A(2B) receptor subtypes, but not the A(3) subtype, was detected in H441 cells and adenosine receptor antagonists could abolish the ATP-evoked stimulation of Na(+) absorption. CONCLUSIONS AND IMPLICATIONS: The ATP-induced stimulation of Na(+) absorption seems to be mediated via A(2A/B) receptors activated by adenosine produced from the extracellular hydrolysis of ATP. The present data thus provide the first description of adenosine-evoked Na(+) transport in airway epithelial cells and reveal a previously undocumented aspect of the control of this physiologically important ion transport process.