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Isoflurane (ISO) is a widely used inhalation anesthetic in experiments with rodents and humans during surgery. Though ISO has not been reported to impart long-lasting side effects, it is unknown if ISO can influence gene regulation in certain tissues, including the heart. Such changes could have important implications for use of this anesthetic in patients susceptible to heart failure/other cardiac abnormalities. To test if ISO could alter gene regulation/expression in heart tissues, and if such changes were reversible, prolonged, or late onset with time, SHR (spontaneously hypertensive) rats were exposed by intratracheal inhalation to a 97.5% air/2.5% ISO mixture on two consecutive days (2 hr/d). Control rats breathed filtered air only. On Days 1, 30, 240, and 360 post-exposure, rat hearts were collected and total RNA was extracted from the left ventricle for global gene expression analysis. The data revealed differentially-expressed genes (DEG) in response to ISO (compared to naïve control) at all post-exposure timepoints. The data showed acute ISO exposures led to DEG associated with wounding, local immune function, inflammation, and circadian rhythm regulation at Days 1 and 30; these effects dissipated by Day 240. There were other significantly-increased DEG induced by ISO at Day 360; these included changes in expression of genes associated with cell signaling, differentiation, and migration, extracellular matrix organization, cell-substrate adhesion, heart development, and blood pressure regulation. Examination of consistent DEG at Days 240 and 360 indicated late onset DEG reflecting potential long-lasting effects from ISO; these included DEG associated with oxidative phosphorylation, ribosome, angiogenesis, mitochondrial translation elongation, and focal adhesion. Together, the data show acute repeated ISO exposures could impart variable effects on gene expression/regulation in the heart. While some alterations self-resolved, others appeared to be long-lasting or late onset. Whether such changes occur in all rat models or in humans remains to be investigated. [ABSTRACT FROM AUTHOR]

The catastrophic destruction of the World Trade Center (WTC) on 11 September 2001 caused the release of high levels of airborne pollutants into the local environment. To assess the toxicity of fine particulate matter [particulate matter with a mass median aerodynamic diameter < 2.5 µm (PM[sub 2.5])], which may adversely affect the health of workers and residents in the area, we collected fallen dust samples on 12 and 13 September 2001 from sites within a half-mile of Ground Zero. Samples of WTC dust were sieved, aerosolized, and size-separated, and the PM[sub 2.5] fraction was isolated on filters. Here we report the chemical and physical properties of PM[sub 2.5] derived from these samples and compare them with PM[sub 2.5] fractions of three reference materials that range in toxicity from relatively inert to acutely toxic (Mt. St. Helens PM; Washington, DC, ambient air PM; and residual oil fly ash). X-ray diffraction of very coarse sieved WTC PM (< 53 µm) identified calcium sulfate (gypsum) and calcium carbonate (calcite) as major components. Scanning electron microscopy confirmed that calcium-sulfur and calcium-carbon particles were also present in the WTC PM[sub 2.5] fraction. Analysis of WTC PM[sub 2.5] using X-ray fluorescence, neutron activation analysis, and inductively coupled plasma spectrometry showed high levels of calcium (range, 22-33%) and sulfur (37-43% as sulfate) and much lower levels of transition metals and other elements. Aqueous extracts of WTC PM[sub 2.5] were basic (pH range, 8.9-10.0) and had no evidence of significant bacterial contamination. Levels of carbon were relatively low, suggesting that combustion-derived particles did not form a significant fraction of these samples recovered in the immediate aftermath of the destruction of the towers. Because gypsum and calcite are known to cause irritation of the mucus membranes of the eyes and respiratory tract, inhalation of high doses of WTC PM[sub 2.5] could potentially cause... [ABSTRACT FROM AUTHOR]

First responders (FRs) present at Ground Zero within the critical first 72 h after the World Trade Center (WTC) collapse have progressively exhibited significant respiratory injury. The majority (>96%) of WTC dusts were >10 μm and no studies have examined potential health effects of this size fraction. This study sought to develop a system to generate and deliver supercoarse (10-53 μm) WTC particles to a rat model in a manner that mimicked FR exposure scenarios. A modified Fishing Line generator was integrated onto an intratracheal inhalation (ITIH) system that allowed for a bypassing of the nasal passages so as to mimic FR exposures. Dust concentrations were measured gravimetrically; particle size distribution was measured via elutriation. Results indicate that the system could produce dusts with 23 μm mass median aerodynamic diameter (MMAD) at levels up to ≥1200 mg/m3. To validate system utility, F344 rats were exposed for 2 h to ≈100 mg WTC dust/m3. Exposed rats had significantly increased lung weight and levels of select tracer metals 1 h after exposure. Using this system, it is now possible to conduct relevant inhalation exposures to determine adverse WTC dusts impacts on the respiratory system. Furthermore, this novel integrated Fishing Line-ITIH system could potentially be used in the analyses of a wide spectrum of other dusts/pollutants of sizes previously untested or delivered to the lungs in ways that did not reflect realistic exposure scenarios. [ABSTRACT FROM AUTHOR]

Background: The WTC collapse exposed over 300,000 people to high concentrations of WTC-PM; particulates up to ∼50 mm were recovered from rescue workers' lungs. Elevated MDC and GM-CSF independently predicted subsequent lung injury in WTC-PM-exposed workers. Our hypotheses are that components of WTC dust strongly induce GM-CSF and MDC in AM; and that these two risk factors are in separate inflammatory pathways. Methodology/Principal Findings: Normal adherent AM from 15 subjects without WTC-exposure were incubated in media alone, LPS 40 ng/mL, or suspensions of WTC-PM10-53 or WTC-PM2.5 at concentrations of 10, 50 or 100 μg/mL for 24 hours; supernatants assayed for 39 chemokines/cytokines. In addition, sera from WTC-exposed subjects who developed lung injury were assayed for the same cytokines. In the in vitro studies, cytokines formed two clusters with GM-CSF and MDC as a result of PM10-53 and PM2.5. GM-CSF clustered with IL-6 and IL-12(p70) at baseline, after exposure to WTC-PM10-53 and in sera of WTC dust-exposed subjects (n = 70) with WTC lung injury. Similarly, MDC clustered with GRO and MCP-1. WTC-PM10-53 consistently induced more cytokine release than WTC-PM2.5 at 100 μg/mL. Individual baseline expression correlated with WTC-PM-induced GM-CSF and MDC. Conclusions: WTC-PM10-53 induced a stronger inflammatory response by human AM than WTC-PM2.5. This large particle exposure may have contributed to the high incidence of lung injury in those exposed to particles at the WTC site. GM-CSF and MDC consistently cluster separately, suggesting a role for differential cytokine release in WTC-PM injury. Subject-specific response to WTC-PM may underlie individual susceptibility to lung injury after irritant dust exposure. [ABSTRACT FROM AUTHOR]

Pollutants originating from the destruction of the World Trade Center (WTC) in New York City on 11 September 2001 have been reported to cause adverse respiratory responses in rescue workers and nearby residents. We examined whether WTC-derived fine particulate matter [particulate matter with a mass median aerodynamic diameter < 2.5 µm (PM[sub 2.5])] has detrimental respiratory effects in mice to contribute to the risk assessment of WTC-derived pollutants. Samples of WTC PM[sub 2.5] were derived from settled dust collected at several locations around Ground Zero on 12 and 13 September 2001. Aspirated samples of WTC PM[sub 2.5] induced mild to moderate degrees of pulmonary inflammation 1 day after exposure but only at a relatively high dose (100 µg). This response was not as great as that caused by 100 µg PM[sub 2.5] derived from residual oil fly ash (ROFA) or Washington, DC, ambient air PM [National Institute of Standards and Technology, Standard Reference Material (SRM) 1649a]. However, this same dose of WTC PM[sub 2.5] caused airway hyperresponsiveness to methacholine aerosol comparable to that from SRM 1649a and to a greater degree than that from ROFA. Mice exposed to lower doses by aspiration or inhalation exposure did not develop significant inflammation or hyperresponsiveness. These results show that exposure to high levels of VWFC PM[sub 2.5] can promote mechanisms of airflow obstruction in mice. Airborne concentrations of WTC PM[sub 2.5] that would cause comparable doses in people are high (∼ 425 µg/m³ for 8 hr) but conceivable in the aftermath of the collapse of the towers when rescue and salvage efforts were in effect. We conclude that a high-level exposure to WTC PM[sub 2.5] could cause pulmonary inflammation and airway hyperresponsiveness in people. The effects of chronic exposures to lower levels of WTC PM[sub 2.5], the persistence of any respiratory effects, and the effects of coarser WTC PM are unknown and were not... [ABSTRACT FROM AUTHOR]

Reports on the assessment of the exposure to dust and smoke among residential and commuter population during the first few days after the September 11, 2001 attack on the World Trade Center in New York City. Determination of the chemical and physical characteristics of the material present in the dust and smoke that settled from the initial plume.

World Trade Center (WTC) responders were exposed to mixture of dust, smoke, chemicals and carcinogens. New York University (NYU) and Mount Sinai have recreated WTC exposure in rodents to observe the resulting systemic and local biological responses. These experiments aid in the interpretation of epidemiological observations and are useful for understanding the carcinogenesis process in the exposed human WTC cohort. Here we describe the implementation of a tissue bank system for the rodents experimentally exposed to WTC dust. NYU samples were experimentally exposed to WTC dust via intratracheal inhalation that mimicked conditions in the immediate aftermath of the disaster. Tissue from Mount Sinai was derived from genetically modified mice exposed to WTC dust via nasal instillation. All processed tissues include annotations of the experimental design, WTC dust concentration/dose, exposure route and duration, genetic background of the rodent, and method of tissue isolation/storage. A biobank of tissue from rodents exposed to WTC dust has been compiled representing an important resource for the scientific community. The biobank remains available as a scientific resource for future research through established mechanisms for samples request and utilization. Studies using the WTC tissue bank would benefit from confirming their findings in corresponding tissues from organs of animals experimentally exposed to WTC dust. Studies on rodent tissues will advance the understanding of the biology of the tumors developed by WTC responders and ultimately impact the modalities of treatment, and the probability of success and survival of WTC cancer patients. [ABSTRACT FROM AUTHOR]