Strain-specific differences in sensitivity to ischemia-reperfusion lung injury in mice

Abstract

Ischemia-reperfusion (I/R) lung injury is characterized by increased pulmonary endothelial permeability and edema, but the genetic basis for this injury is unknown. We utilized an in vivo mouse preparation of unilateral lung I/R to evaluate the genetic determinants of I/R lung injury. An index of pulmonary vascular protein permeability was measured by the ratio of left-to-right lung Evans blue dye of eight inbred mouse strains after 30 min of left lung ischemia and 150 min of reperfusion. The order of strain-specific sensitivity to I/R lung injury was BALB/c < SJL/J < CBA/J < C57BL/6J < 129/J < A/J < C3H/H3J < SWR/J. The reciprocal F1 offspring of the BALB/c and SWR/J progenitor strains had intermediate phenotypes but a differing variance. A similar pattern of right lung Evans blue dye content suggested the presence of contralateral injury because baseline vascular permeability was not different. Lung I/R injury was attenuated by NADPH oxidase inhibition, indicating a role for NADPH oxidase-derived reactive oxygen species (ROS). There was no strain-dependent difference in lung NADPH oxidase expression. Strain-related differences in zymosan-stimulated neutrophil ROS production did not correlate with I/R lung injury in that neutrophil ROS production in SWR/J mice was greater than C57BL/6J but not different from BALB/c mice. These data indicate the presence of a genetic sensitivity to lung I/R injury that involves multiple genes including a maternal-related factor. Although neutrophil-derived ROS production is also modulated by genetic factors, the pattern did not explain the genetic sensitivity to lung I/R injury.

Interactive effects of mechanical ventilation and kidney health on lung function in an in vivo mouse model

“…Optical density, measured with a microplate reader (Organon Teknika, Durham, NC), was reported as "arbitrary units." We confirmed that the relationship of EBD concentration and optical density at 620 nm was linear (R ϭ 0.999) through the range of absorbance values encompassed by our lung samples by constructing a seven-point standard curve (9,10,24).…”

Developmental Regulation of NO-Mediated VEGF-Induced Effects in the Lung

“…The noted values represent assessments in a minimum of four infants at each time point. **P < 0.01; # P , 0.02; ## P < 0.05. other model systems (40)(41)(42)(43), as well as the timing. Importantly, our studies also demonstrate that the effects on surfactant were not mediated by NO, as they were not altered by the NOSbased intervention that was employed.…”

Effect of temperature control upon a mouse model of partial hepatic ischaemia/reperfusion injury

“…Variables previously shown to affect performance in response to hepatic IRI are animal sex (Harada et al 2004) strain (Burne et al 2000, Shireman & Quinones 2005, Dodd et al 2006) and intraoperative temperature regulation (Biberthaler et al 2001, Kato et al 2002, Khandoga et al 2003. These factors have been tested in heterogeous models of hepatic IRI, and as a result, experiments cannot be directly compared; their results are difficult to apply directly to the development of new experimental models.…”