To study the effect of ventilation strategy on perfluorochemical (PFC) elimination profile (evaporative loss profile; E(L)), 6 ml/kg of perflubron were instilled into anesthetized normal rabbits. The strategy was to maintain minute ventilation (VE, in ml/min) in three groups: VE(L) (low-range VE, 208 +/- 2), VE(M) (midrange VE, 250 +/- 9), and VE(H) (high-range VE, 293 +/- 1) over 4 h. In three other groups, respiratory rate (RR, breaths/min) was controlled at 20, 30, or 50 with a constant VE and adjusted tidal volume. PFC content in the expired gas was measured, and E(L) was calculated. There was a significant VE- and time-dependent effect on E(L.) Initially, percent PFC saturation and loss rate decreased in the VE(H) > VE(M) > VE(L) groups, but by 3 h the lower percent PFC saturation resulted in a loss rate such that VE(H) < VE(M) < VE(L) at 4 h. For the groups at constant VE, there was a significant time effect on E(L) but no RR effect. In conclusion, E(L) profile is dependent on VE with little effect of the RR-tidal volume combination. Thus measurement of E(L) and VE should be considered for the replacement dosing schemes during partial liquid ventilation.

This study demonstrates that this unique polyaxial locking plate mechanism, when tested in various constructs, exhibits similar biomechanical performance regarding stiffness, strength to failure, and resistance to plastic deformation when compared with uniaxial locking plates. The polyaxial locking plate with an angled screw was stiffest and had the greatest load to failure. The polyaxial locking plate alone tested similar to the LISS. In addition, the benefit of the angled screw for biomechanical stability is demonstrated.

Patients with pulmonary infection often present with ventilation and perfusion abnormalities, which can impair intravenous antibiotic therapy. Intra-tracheal (i.t.) administration has met with obstacles, such as inadequate delivery to affected lung regions and the disruption of gas exchange. We hypothesized that i.t. administration of a gentamicin (G)/perfluorochemical (PFC) suspension (G/PFC) would effectively deliver and distribute gentamicin to the lung, while maintaining gas exchange and non-toxic serum levels. In addition, we sought to compare serum G and lung levels and distribution of G when G/PFC is administered at the initiation of partial liquid ventilation (PLV) vs. during PLV. To test this hypothesis, 17 newborn lambs were ventilated by PLV with perflubron (LiquiVent) for 4 h using three different G (5 mg kg-1) administration techniques: i.t. slow-fill (SF) (n = 6; G/PFC over 15 min at start of PLV), i.t. top-fill (TF) (n = 6; G/PFC 10-65 min after start of PLV), intravenous (i.v.) (n = 5, aqueous injection at start of PLV). Serum levels of gentamicin were obtained 1, 15, 30 and 60 min after administration, and hourly there after for the remainder of the protocol (4 h). Arterial blood gas and pulmonary function measurements were obtained throughout the protocol. At the conclusion of the protocol, representative samples from each lung lobe, the brain and kidney were homogenized and assayed for gentamicin. All results are presented as the mean +/- SEM; P< 0.05. Over time, serum gentamicin levels were greatest (P < 0.05) in i.v. (11.0 +/- 2.3 micrograms ml-1), followed by TF (2.3 +/- 0.1 micrograms ml-1) and SF (0.8 +/- 0.1 microgram ml-1). The percentage of the administered dose remaining in the lungs after 4 h was greater (P < 0.05) following i.t. delivery (SF 23.8 +/- 4.3%, TF 13.7 +/- 2.5%) as compared to i.v. (3.7 +/- 0.5%). These findings suggest that for a given dose of G, both SF and TF delivery methods of G/PFC can enhance pulmonary, relative to systemic, antibiotic coverage.

Preterm infants exposed to mechanical ventilation often develop airway dysfunction and bronchopulmonary dysplasia. The mechanisms of mechanical ventilation-induced airway injury are currently unknown. This study correlates the age-related effects of mechanical ventilation on airway function with structural alterations at the tissue, cellular, ultrastructural, and molecular levels. Mechanically ventilated and nonventilated tracheal rings were obtained from premature and newborn lambs. In tissue baths, the passive and active length-tension relationships and dose-response characteristics of the tracheal rings were determined. Fixed tracheal rings were digested and the resulting isolated smooth muscle cells measured. Rings were analyzed by light and electron microscopy. Additionally, protein was extracted from the tracheal smooth muscle and myosin heavy chain isoforms were separated by SDS-polyacrylamide gel electrophoresis and analyzed by densitometry. Mechanical ventilation resulted in a significant decrease of both the slope of the passive length-stress relationship and of maximal force generation, with both effects being most pronounced in the newborn age group. These age-related functional alterations correlated with a decrease in smooth muscle cell length and a disruption of ultrastructural architecture, which were also most pronounced in the older groups. Furthermore, mechanical ventilation resulted in epithelial denudation at all ages. There were no acute statistically significant effects of mechanical ventilation on myosin heavy chain isoform expression. This study demonstrates age-related effects of mechanical ventilation on the passive and active characteristics of tracheal function and provides a structural analysis of potential mechanisms. The mechanisms behind these functional differences involve ultrastructural changes in cell length, tissue matrix, and disruption of epithelial integrity. These findings help elucidate the pathogenesis of ventilator-induced airway injury.

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