Dynamic airway constriction in rats: heterogeneity and response to deep inspiration.

Airway narrowing due to hyperresponsiveness severely limits gas exchange in patients with asthma. Imaging studies in humans and animals have shown that bronchoconstriction causes patchy patterns of ventilation defects throughout the lungs, and several computational models have predicted that these regions are due to constriction of smaller airways. However, these imaging approaches are often limited in their ability to capture dynamic changes in small airways, and the patterns of constriction are heterogeneous.

Model development and use of ACE inhibitors for preclinical mitigation of radiation-induced injury to multiple organs.

The NIH/NIAID initiated a countermeasure program to develop mitigators for radiation-induced injuries from a radiological attack or nuclear accident. We have previously characterized and demonstrated mitigation of single organ injuries, such as radiation pneumonitis, pulmonary fibrosis or nephropathy by angiotensin converting enzyme (ACE) inhibitors. Our current work extends this research to examine the potential for mitigating multiple organ dysfunctions occurring in the same irradiated rats.

Enalapril mitigates focal alveolar lesions, a histological marker of late pulmonary injury by radiation to the lung.

The goal of our study was to identify a histological marker for testing countermeasures for mitigation of late radiation injury to the lung. Pulmonary fibrosis is currently the best described "late effect" in survivors of acute radiation pneumonitis. However, robust fibrosis does not develop in some rodent strains for years after a single dose of radiation to the whole thorax.

Short-term treatment with a SOD/catalase mimetic, EUK-207, mitigates pneumonitis and fibrosis after single-dose total-body or whole-thoracic irradiation.

In the event of a radiological accident or terrorist attack, whole- or partial-body exposure can injure the lungs. To simulate such an incident, we used a single fraction of total-body irradiation (TBI) or whole-thoracic irradiation to induce pneumonitis or pulmonary fibrosis, respectively, in a rat model. The superoxide dismutase and catalase mimetic EUK-207 was given by subcutaneous injection (20 mg/kg/day, 5 days per week, once daily) starting at 7 days after irradiation and stopping before pneumonitis developed.

Mitigation of radiation induced pulmonary vascular injury by delayed treatment with captopril.

Background And Objective: A single dose of 10 Gy radiation to the thorax of rats results in decreased total lung angiotensin-converting enzyme (ACE) activity, pulmonary artery distensibility and distal vascular density while increasing pulmonary vascular resistance (PVR) at 2 months post-exposure. In this study, we evaluate the potential of a renin-angiotensin system (RAS) modulator, the ACE inhibitor captopril, to mitigate this pulmonary vascular damage.

Methods: Rats exposed to 10 Gy thorax only irradiation and age-matched controls were studied 2 months after exposure, during the development of radiation pneumonitis.

Persistent vascular collagen accumulation alters hemodynamic recovery from chronic hypoxia.

Pulmonary arterial hypertension (PAH) is caused by narrowing and stiffening of the pulmonary arteries that increase pulmonary vascular impedance (PVZ). In particular, small arteries narrow and large arteries stiffen. Large pulmonary artery (PA) stiffness is the best current predictor of mortality from PAH.

Multimodality imaging of abnormal vascular perfusion and morphology in preclinical 9L gliosarcoma model.

Background: This study demonstrates that a dynamic susceptibility contrast-magnetic resonance imaging (DSC-MRI) perfusion parameter may indicate vascular abnormality in a brain tumor model and reflects an effect of dexamethasone treatment. In addition, X-ray computed tomography (CT) measurements of vascular tortuosity and tissue markers of vascular morphology were performed to investigate the underpinnings of tumor response to dexamethasone.

Methodology/principal Findings: One cohort of Fisher 344 rats (N = 13), inoculated intracerebrally with 9L gliosarcoma cells, was treated with dexamethasone (i.

Distribution of capillary transit times in isolated lungs of oxygen-tolerant rats.

Rats pre-exposed to 85% O₂ for 5-7 days tolerate the otherwise lethal effects of 100% O₂. The objective was to evaluate the effect of rat exposure to 85% O₂ for 7 days on lung capillary mean transit time t(c) and distribution of capillary transit times (h(c)(t)). This information is important for subsequent evaluation of the effect of this hyperoxia model on the redox metabolic functions of the pulmonary capillary endothelium.

Discriminating pulmonary hypertension caused by monocrotaline toxicity from chronic hypoxia by near-infrared spectroscopy and multivariate methods of analysis.

A new method has been developed for the determination of tissue pathology caused by chronic hypoxia and monocrotaline toxicity. The method is based on the use of near-infrared (NIR) spectrophotometry to measure spectra of lung tissue from normal chronic hypoxia (CH) and monocrotaline (MCT) models of pulmonary hypertension (PH), followed by analysis using multivariate methods, that is, principal component analysis (PCA) and partial least squares (PLS). Synergistic use of NIR with the PCA/PLS method makes it possible, for the first time, not only to divide different lung tissue samples into their respective groups (normal, CH, and MCT) but also to gain insight into mechanisms of PH caused by CH and MCT toxicity.

Site-specific effects of PECAM-1 on atherosclerosis in LDL receptor-deficient mice.

Objective: Atherosclerosis is a vascular disease that involves lesion formation at sites of disturbed flow under the influence of genetic and environmental factors. Endothelial expression of adhesion molecules that enable infiltration of immune cells is important for lesion development. Platelet/endothelial cell adhesion molecule-1 (PECAM-1; CD31) is an adhesion and signaling receptor expressed by many cells involved in atherosclerotic lesion development.

Irradiation of varying volumes of rat lung to same mean lung dose: a little to a lot or a lot to a little?

Purpose: To investigate whether irradiating small lung volumes with a large dose or irradiating large lung volumes with a small dose, given the same mean lung dose (MLD), has a different effect on pulmonary function in laboratory animals.

Methods And Materials: WAG/Rij/MCW male rats were exposed to single fractions of 300 kVp X-rays. Four treatments, in decreasing order of irradiated lung volume, were administered: (1) whole lung irradiation, (2) right lung irradiation, (3) left lung irradiation, and (4) irradiation of a small lung volume with four narrow beams.

Bronchial circulation angiogenesis in the rat quantified with SPECT and micro-CT.

Introduction: As pulmonary artery obstruction results in proliferation of the bronchial circulation in a variety of species, we investigated this angiogenic response using single photon emission computed tomography (SPECT) and micro-CT.

Materials And Methods: After surgical ligation of the left pulmonary artery of rats, they were imaged at 10, 20, or 40 days post-ligation. Before imaging, technetium-labeled macroaggregated albumin ((99m)Tc MAA) was injected into the aortic arch (IA) labeling the systemic circulation.

Airway strain during mechanical ventilation in an intact animal model.

Rationale: Mechanical ventilation with large tidal volumes causes ventilator-induced lung injury in animal models. Little direct evidence exists regarding the deformation of airways in vivo during mechanical ventilation, or in the presence of positive end-expiratory pressure (PEEP).

Objectives: To measure airway strain and to estimate airway wall tension during mechanical ventilation in an intact animal model.

99mTc-labeled C2A domain of synaptotagmin I as a target-specific molecular probe for noninvasive imaging of acute myocardial infarction.

Unlabelled: The exposure of phosphatidylserine (PtdS) is a common molecular marker for both apoptosis and necrosis and enables the simultaneous detection of these distinct modes of cell death. Our aim was to develop a radiotracer based on the PtdS-binding activity of the C2A domain of synaptotagmin I and assess 99mTc-C2A-GST (GST is glutathione S-transferase) using a reperfused acute myocardial infarction (AMI) rat model.

Methods: The binding of C2A-GST toward apoptosis and necrosis was validated in vitro.

A simple, inexpensive, and effective light- carrying laryngoscopic blade for orotracheal intubation of rats.

The research paradigm of using large laboratory animals, in which oroendotracheal intubations are relatively easy, is shifting toward the use of small animals, such as rodents, in which oropharyngeal access is limited, the arytenoid cartilage cycles are faster, and the glottis is much smaller. The considerable growth recently seen in preclinical imaging studies is accompanied by an increased number of rats and mice requiring in vivo intubation for airway management. Tracheal access is important for ventilation, administration of inhaled anesthetics, instillation of drugs or imaging agents, and maintenance of airway patency to reduce mortality during and after operations.

Microfocal X-ray computed tomography post-processing operations for optimizing reconstruction volumes of stented arteries during 3D computational fluid dynamics modeling.

Restenosis caused by neointimal hyperplasia (NH) remains an important clinical problem after stent implantation. Restenosis varies with stent geometry, and idealized computational fluid dynamics (CFD) models have indicated that geometric properties of the implanted stent may differentially influence NH. However, 3D studies capturing the in vivo flow domain within stented vessels have not been conducted at a resolution sufficient to detect subtle alterations in vascular geometry caused by the stent and the subsequent temporal development of NH.

Alterations in wall shear stress predict sites of neointimal hyperplasia after stent implantation in rabbit iliac arteries.

Restenosis resulting from neointimal hyperplasia (NH) limits the effectiveness of intravascular stents. Rates of restenosis vary with stent geometry, but whether stents affect spatial and temporal distributions of wall shear stress (WSS) in vivo is unknown. We tested the hypothesis that alterations in spatial WSS after stent implantation predict sites of NH in rabbit iliac arteries.

Dynamic small animal lung imaging via a postacquisition respiratory gating technique using micro-cone beam computed tomography.

Rationale And Objectives: Micro computed tomography is an important tool for small animal imaging. On many occasions, it is desirable to image lungs in a live instead of postmortem small animal to perform a pulmonary physiology study. Because the lungs are moving, gating with respect to the ventilatory phase has to be performed to reduce motion artifacts.

Quantitative models of the rat pulmonary arterial tree morphometry applied to hypoxia-induced arterial remodeling.

Little is known about the constituent hemodynamic consequences of structural changes that occur in the pulmonary arteries during the onset and progression of pulmonary arterial remodeling. Many disease processes are known to be responsible for vascular remodeling that leads to pulmonary arterial hypertension, cor pulmonale, and death. Histology has been the primary tool for evaluating pulmonary remodeling, but it does not provide information on intact vascular structure or the vessel mechanical properties.

Effect of ventilation rate on instilled surfactant distribution in the pulmonary airways of rats.

Liquid can be instilled into the pulmonary airways during medical procedures such as surfactant replacement therapy, partial liquid ventilation, and pulmonary drug delivery. For all cases, understanding the dynamics of liquid distribution in the lung will increase the efficacy of treatment. A recently developed imaging technique for the study of real-time liquid transport dynamics in the pulmonary airways was used to investigate the effect of respiratory rate on the distribution of an instilled liquid, surfactant, in a rat lung.