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An Improved Method for Rapid Intubation of the Trachea in Mice

Despite some anatomical and physiological differences, mouse models continue to be an essential tool for studying human lung disease. Bleomycin toxicity ...

University of Washington

This report validates the use and limitations of the Nonin Pulse Oximeter for measuring heart rate and oxygen saturation in rats. Eight anesthetized Sprague-Dawley rats were intubated and catheterized. Oxygen saturation was directly measured from arterial blood by using a Radiometer OSM3 Hemoximeter adjusted for rat blood as well as indirectly by using the Nonin Pulse Oximeter. Oxygen saturation was changed by varying the level of inhaled oxygen. Heart rate was measured in two ways: 1) by using the signal from the Nonin Pulse Oximeter and 2) by counting the pressure pulses from the transduced blood pressure. There was excellent agreement between heart rate values measured by the Nonin Pulse Oximeter and that measured by counting the pulses from the arterial blood pressure recording. The Nonin Pulse Oximeter underestimated oxygen saturations by about 3% to 5% compared to the Hemoximeter. Overall, the pulse oximeter reflected important trends in oxygen saturations, making it a useful tool for laboratory animal medicine.

Validation of the Nonin 8600V Pulse Oximeter for heart rate and oxygen saturation measurements in rats.

Perioperative ischemic optic neuropathy occurs after major surgical procedures, which are often associated with hypotension, anemia, or venous congestion. However, the effects of these conditions on optic nerve (ON) blood flow are unknown and cannot be studied adequately in humans.

Effects of anemia and hypotension on porcine optic nerve blood flow and oxygen delivery.

Cysteine-rich protein-61 (CYR61), also known as CCN1, is a heparin-binding protein member of the CCN family of matricellular proteins. Gene expression profiles showed that Cyr61 is upregulated in acute human lung injury (ALI), but its functional role is unclear. We hypothesized that CYR61 contributes to ALI in mice. First, we demonstrated that CYR61 expression increases after bleomycin-induced lung injury. We then used adenovirus-mediated gene transfer to determine whether CYR61 over-expression in the lungs was sufficient to cause ALI. Mice instilled with adenovirus AdCyr61 showed greater weight loss, increased bronchoalveolar lavage (BAL) total neutrophil counts, increased protein concentrations and increased mortality compared to mice instilled with empty vector adenovirus. Immunohistochemical studies in lungs from humans with idiopathic pulmonary fibrosis (IPF) revealed CYR61 expression on the luminal membrane of alveolar epithelial cells in areas of injury. We conclude that CYR61 is upregulated in ALI and that CYR61 over-expression exacerbates ALI in mice.

CYR61 (CCN1) OVEREXPRESSION INDUCES LUNG INJURY IN MICE.

The Tie2/angiopoietin (Tie2/Ang) and vascular endothelial growth factor receptor-ligand systems (VEGFR/VEGF) are recognized to play important roles in the regulation of microvascular endothelial function. Downregulation of these genes during sepsis has been implicated in the pathogenesis of sepsis-related microvascular leak and multiple organ dysfunction syndrome. Mechanisms responsible for dysregulation of angiogenic genes in sepsis are poorly defined.

Experimental acute lung injury induces multi-organ epigenetic modifications in key angiogenic genes implicated in sepsis-associated endothelial dysfunction.

Exposure to inhaled allergens generates T helper 2 (Th2) CD4(+) T cells that contribute to episodes of inflammation associated with asthma. Little is known about allergen-specific Th2 memory cells and their contribution to airway inflammation. We generated reagents to understand how endogenous CD4(+) T cells specific for a house dust mite (HDM) allergen form and function. After allergen exposure, HDM-specific memory cells persisted as central memory cells in the lymphoid organs and tissue-resident memory cells in the lung. Experimental blockade of lymphocyte migration demonstrated that lung-resident cells were sufficient to induce airway hyper-responsiveness, which depended upon CD4(+) T cells. Investigation into the differentiation of pathogenic Trm cells revealed that interleukin-2 (IL-2) signaling was required for residency and directed a program of tissue homing migrational cues. These studies thus identify IL-2-dependent resident Th2 memory cells as drivers of lung allergic responses.

Dowon An

Division of Pulmonary and Critical Care Medicine

University of Washington

An Improved Method for Rapid Intubation of the Trachea in Mice