Total liquid ventilation provides superior respiratory support to conventional mechanical ventilation in a large animal model of severe respiratory failure.

Total liquid ventilation (TLV) has the potential to provide respiratory support superior to conventional mechanical ventilation (CMV) in the acute respiratory distress syndrome (ARDS). However, laboratory studies are limited to trials in small animals for no longer than 4 hours. The objective of this study was to compare TLV and CMV in a large animal model of ARDS for 24 hours. Ten sheep weighing 53 ± 4 (SD) kg were anesthetized and ventilated with 100% oxygen. Oleic acid was injected into the pulmonary circulation until PaO2:FiO2 ≤ 60 mm Hg, followed by transition to a protective CMV protocol (n = 5) or TLV (n = 5) for 24 hours. Pathophysiology was recorded, and the lungs were harvested for histological analysis. Animals treated with CMV became progressively hypoxic and hypercarbic despite maximum ventilatory support. Sheep treated with TLV maintained normal blood gases with statistically greater PO2 (p < 10(-9)) and lower PCO2 (p < 10(-3)) than the CMV group. Survival at 24 hours in the TLV and CMV groups were 100% and 40%, respectively (p < 0.05). Thus, TLV provided gas exchange superior to CMV in this laboratory model of severe ARDS.

A novel, low cost, disposable, pediatric pulsatile rotary ventricular pump for cardiac surgery that provides a physiological flow pattern.

Research is underway to develop a novel, low cost, disposable pediatric pulsatile rotary ventricular pump (PRVP) for cardiac surgery that provides a physiological flow pattern. This is believed to offer reduced morbidity and risk exposure within this population. The PRVP will have a durable design suitable for use in short- to mid-length prolonged support after surgery without changing pumps. The design is based on proprietary MC3 technology which provides variable pumping volume per stroke, thereby allowing the pump to respond to hemodynamic status changes of the patient. The novel pump design also possesses safety advantages that prevent retrograde flow, and maintain safe circuit pressures upon occlusion of the inlet and outlet tubing. The design is ideal for simple, safe and natural flow support. Computational methods have been developed that predict output for pump chambers of varying geometry. A scaled chamber and pump head (diameter = 4 in) were prototyped to demonstrate target performance for pediatrics (2 L/min at 100 rpm). A novel means of creating a pulsatile flow and pressure output at constant RPM was developed and demonstrated to create significant surplus hydraulic energy (>10%) in a simplified mock patient circuit.

Nitric oxide-releasing fumed silica particles: synthesis, characterization, and biomedical application.

The preparation, characterization, and preliminary biomedical application of various nitric oxide (NO)-releasing fumed silica particles (0.2-0.3 microm) are reported. The tiny NO-releasing particles are synthesized by first tethering alkylamines onto the surface of the silica using amine-containing silylation reagents. These amine groups are then converted to corresponding N-diazeniumdiolate groups via reaction with NO(g) at high pressure in the presence of methoxide bases (e.g., NaOMe). N-Diazeniumdiolate groups were found to form more readily with secondary amino nitrogens than primary amino nitrogens tethered to the silica. Different alkali metal cations of the methoxide bases, however, have little effect on the degree of N-diazeniumdiolate formation. The N-diazeniumdiolate moieties attached on the silica surface undergo a primarily proton-driven dissociation to NO under physiological conditions, with an "apparent" reaction order somewhat greater than 1 owing to local increases in pH at the surface of the particles as free amine groups are generated. The rates of N-diazeniumdiolate dissociation are further related to the parent amine structures and the pH of the soaking buffer. The N-diazeniumdiolate groups also undergo slow thermal dissociation to NO, with zero-order dissociation observed at both -15 and 23 degrees C. It is further shown that the resulting NO-releasing fumed silica particles can be embedded into polymer films to create coatings that are thromboresistant, via the release of NO at fluxes that mimic healthy endothelial cells (EC). For example a polyurethane coating containing 20 wt % of NO-releasing particles prepared with pendant hexane diamine structure (i.e., Sil-2N[6]-N(2)O(2)Na) is shown to exhibit improved surface thromboresistivity (compared to controls) when used to coat the inner walls of extracorporeal circuits (ECC) employed in a rabbit model for extracorporeal blood circulation.

Nitric oxide releasing silicone rubbers with improved blood compatibility: preparation, characterization, and in vivo evaluation.

Nitric oxide (NO) releasing silicone rubbers (SR) are prepared via a three-step reaction scheme. A diamino triaminoalkyltrimethoxysilane crosslinker is used to vulcanize hydroxyl terminated polydimethylsiloxane (PDMS) in the presence of ambient moisture and a dibutyltin dilaurate catalyst so that the respective diamine triamine groups are covalently linked to the cured SR structure. These amine sites are then diazeniumdiolated, in situ, when the cured SR is reacted with NO at elevated pressure (80 psi). Although nitrite species are also formed during the NO addition reaction, in most cases the diazeniumdiolated polymer is the major product within the final SR matrix. Temperature appears to be the major driving force for the dissociation of the attached diazeniumdiolate moieties, whereas the presence of bulk water bathing the SR materials has only minimal effect on the observed NO release rate owing to the low water uptake of the SR matrices. The resulting SR films/coatings release NO at ambient or physiological temperature for up to 20 d with average fluxes of at least 4 x 10(10) mol x cm(-2) x min(-1) (coating thickness > or = 600 microm) over first 4 h, comparable to the NO fluxes observed from stimulated human endothelial cells. The NO loading and concomitant NO release flux of the SR material are readily adjustable by altering the diamine triamine loading and film/coating thickness. The new NO releasing SR materials are shown to exhibit improved thromboresistance in vivo, as demonstrated via reduced platelet activation on the surface of these polymers when used to coat the inner walls of SR tubings employed for extracorporeal circulation in a rabbit model.