This paper compares and describes the tidal volume (Vt) used in mechanically ventilated dogs under a range of clinical conditions. Twenty-eight dogs requiring mechanical ventilation (MV) were classified into 3 groups: healthy dogs mechanically ventilated during surgery (group I, n = 10), dogs requiring MV due to extra-pulmonary reasons (group II, n = 7), and dogs that required MV due to pulmonary pathologies (group III, n = 11). The median Vt used in each group was 16 mL/kg (interquartile range [IQR], 15.14–21) for group I, 12.59 mL/kg (IQR, 9–14.25) for group II, and 12.59 mL/kg (IQR, 10.15–14.96) for group III. The Vt used was significantly lower in group III than in group I (p = 0.016). The thoraco-pulmonary compliance was significantly higher in group I than in groups II and III (p = 0.011 and p = 0.006, respectively). The median driving pressure was similar among the groups with a median of 9, 11, and 10 cmH2O in groups I, II, and III, respectively (p = 0.260). Critically-ill dogs requiring MV due to the primary pulmonary pathology received a significantly lower Vt than healthy dogs but with a range of values that were markedly higher than those recommended by human guidelines.
Animals ; Compliance ; Dogs ; Humans ; Pathology ; Respiration, Artificial ; Tidal Volume ; Ventilator-Induced Lung Injury

The lysosome is responsible for protein and organelle degradation and homeostasis and the cathepsins play a key role in maintaining protein quality control. Cathepsin D (CTSD), is one such lysosomal protease, which when deficient in humans lead to neurolipofuscinosis (NCL) and is important in removing toxic protein aggregates. Prior studies demonstrated that CTSD germ-line knockout-CtsdKO (CDKO) resulted in accumulation of protein aggregates, decreased proteasomal activities, and postnatal lethality on Day 26 ± 1. Overexpression of wildtype CTSD, but not cathepsin B, L or mutant CTSD, decreased α-synuclein toxicity in worms and mammalian cells. In this study we generated a mouse line expressing human CTSD with a floxed STOP cassette between the ubiquitous CAG promoter and the cDNA. After crossing with Nestin-cre, the STOP cassette is deleted in NESTIN + cells to allow CTSD overexpression-CTSDtg (CDtg). The CDtg mice exhibited normal behavior and similar sensitivity to sub-chronic 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) induced neurodegeneration. By breeding CDtg mice with CDKO mice, we found that over-expression of CTSD extended the lifespan of the CDKO mice, partially rescued proteasomal deficits and the accumulation of Aβ42 in the CDKO. This new transgenic mouse provides supports for the key role of CTSD in protecting against proteotoxicity and offers a new model to study the role of CTSD enhancement in vivo.