A radiomic model to classify response to neoadjuvant chemotherapy in breast cancer.

BACKGROUND: Medical image analysis has evolved to facilitate the development of methods for high-throughput extraction of quantitative features that can potentially contribute to the diagnostic and treatment paradigm of cancer. There is a need for further improvement in the accuracy of predictive markers of response to neo-adjuvant chemotherapy (NAC). The aim of this study was to develop a radiomic classifier to enhance current approaches to predicting the response to NAC breast cancer. METHODS: Data on patients treated for breast cancer with NAC prior to surgery who had a pre-NAC dynamic contrast enhanced breast MRI were included. Response to NAC was assessed using the Miller-Payne system on the excised tumor. Tumor segmentation was carried out manually under the supervision of a consultant breast radiologist. Features were selected using least absolute shrinkage selection operator regression. A support vector machine learning model was used to classify response to NAC. RESULTS: 74 patients were included. Patients were classified as having a poor response to NAC (reduction in cellularity < 90%, n = 44) and an excellent response (> 90% reduction in cellularity, n = 30). 4 radiomics features (discretized kurtosis, NGDLM contrast, GLZLM_SZE and GLZLM_ZP) were identified as pertinent predictors of response to NAC. A SVM model using these features stratified patients into poor and excellent response groups producing an AUC of 0.75. Addition of estrogen receptor status improved the accuracy of the model with an AUC of 0.811. CONCLUSION: This study identified a radiomic classifier incorporating 4 radiomics features to augment subtype based classification of response to NAC in breast cancer.

The development and structure of the mesentery.

The position of abdominal organs, and mechanisms by which these are centrally connected, are currently described in peritoneal terms. As part of the peritoneal model of abdominal anatomy, there are multiple mesenteries. Recent findings point to an alternative model in which digestive organs are connected to a single mesentery. Given that direct evidence of this is currently lacking, we investigated the development and shape of the entire mesentery. Here we confirm that, within the abdomen, there is one mesentery in which all abdominal digestive organs develop and remain connected to. We show that all abdominopelvic organs are organised into two, discrete anatomical domains, the mesenteric and non-mesenteric domain. A similar organisation occurs across a range of animal species. The findings clarify the anatomical foundation of the abdomen; at the foundation level, the abdomen comprises a visceral (i.e. mesenteric) and somatic (i.e. musculoskeletal) frame. The organisation at that level is a fundamental order that explains the positional anatomy of all abdominopelvic organs, vasculature and peritoneum. Collectively, the findings provide a novel start point from which to systemically characterise the abdomen and its contents.

Development of a large-scale computer-controlled ozone inhalation exposure system for rodents.

Objective: Complete systems for laboratory-based inhalation toxicology studies are typically not commercially available; therefore, inhalation toxicologists utilize custom-made exposure systems. Here we report on the design, construction, testing, operation and maintenance of a newly developed in vivo rodent ozone inhalation exposure system. Materials and methods: Key design requirements for the system included large-capacity exposure chambers to facilitate studies with large sample sizes, automatic and precise control of chamber ozone concentrations, as well as automated data collection on airflow and environmental conditions. The exposure system contains two Hazelton H-1000 stainless steel and glass exposure chambers, each providing capacity for up to 180 mice or 96 rats. We developed an empirically tuned proportional-integral-derivative control loop that provides stable ozone concentrations throughout the exposure period (typically 3h), after a short ramp time (∼8 min), and across a tested concentration range of 0.2-2 ppm. Specific details on the combination of analog and digital input/output system for environmental data acquisition, control and safety systems are provided, and we outline the steps involved in maintenance and calibration of the system. Results: We show that the exposure system produces consistent ozone exposures both within and across experiments, as evidenced by low coefficients of variation in chamber ozone concentration and consistent biological responses (airway inflammation) in mice, respectively. Conclusion: Thus, we have created a large and robust ozone exposure system, facilitating future studies on the health effects of ozone in rodents.

3D modelling of non-intestinal colorectal anatomy.

PURPOSE: There is a paucity of methods to model soft anatomical tissues. Accurate modelling of these tissues can be difficult with current medical imaging technology. METHODS: The aim of this research was to develop a methodology to model non-intestinal colorectal tissues that are not readily identifiable radiologically to enhance contextual understanding of these tissues and inform medical device design. The models created were used to inform the design of a novel medical device to separate the mesocolon from the retroperitoneum during resection of the colon. We modelled the peritoneum and the mesentery. The mesentery was used to indicate the location of Toldt's fascia. RESULTS: We generated a point cloud dataset using cryosection images as the target anatomy is more visible than in CT or MRI images. The thickness of the mesentery could not be accurately determined as point cloud data do not have thickness. A denser point cloud detailing the mesenteric boundaries could be used to address this. CONCLUSIONS: Expert anatomical and surgical insight and point cloud data modelling methods can be used to model soft tissues. This research enhances the overall understanding of the mesentery and Toldt's fascia in the human specimen which is necessary for medical device innovations for colorectal surgical procedures.

Ambient Particulate Matter and Acrolein Co-Exposure Increases Myocardial Dyssynchrony in Mice via TRPA1.

Air pollution is a complex mixture of particulate matter and gases linked to adverse clinical outcomes. As such, studying responses to individual pollutants does not account for the potential biological responses resulting from the interaction of various constituents within an ambient air shed. We previously reported that exposure to high levels of the gaseous pollutant acrolein perturbs myocardial synchrony. Here, we examined the effects of repeated, intermittent co-exposure to low levels of concentrated ambient particulates (CAPs) and acrolein on myocardial synchrony and the role of transient receptor potential cation channel A1 (TRPA1), which we previously linked to air pollution-induced sensitization to triggered cardiac arrhythmia. Female B6129 and Trpa1-/- mice (n = 6/group) were exposed to filtered air (FA), CAPs (46 µg/m3 of PM2.5), Acrolein (0.42 ppm), or CAPs+Acrolein for 3 h/day, 2 days/week for 4 weeks. Cardiac ultrasound was conducted to assess cardiac synchronicity and function before and after the first exposure and after the final exposure. Heart rate variability (HRV), an indicator of autonomic tone, was assessed after the final exposure. Strain delay (time between peak strain in adjacent cardiac wall segments), an index of myocardial dyssynchrony, increased by 5-fold after the final CAPs+Acrolein exposure in B6129 mice compared with FA, CAPs, or Acrolein-exposed B6129 mice, and CAPs+Acrolein-exposed Trpa1-/- mice. Only exposure to acrolein alone increased the HRV high frequency domain (5-fold) in B6129 mice, but not in Trpa1-/- mice. Thus, repeated inhalation of pollutant mixtures may increase risk for cardiac responses compared with single or multiple exposures to individual pollutants through TRPA1 activation.

Insight into the perioperative management of direct oral anticoagulants: concerns and considerations.

INTRODUCTION: Direct oral anticoagulants (DOACs) have gained momentum in recent years in patients requiring anticoagulation for the prevention and management of venous thromboembolism and thromboembolic events caused by atrial fibrillation. The use of these agents involves potential bleeding complications, particularly during invasive procedures. With increasing use of DOACs, adequate knowledge regarding the perioperative management of patients on DOACs has become indispensable. AREAS COVERED: This review covers the indications, mechanism of action, and pharmacokinetics of DOACs and their management in different perioperative settings based on various current guidelines and practices. The role of bridging therapy with heparin and the recently developed reversal agents are also discussed. EXPERT OPINION: The perioperative management of DOACs is influenced by drug pharmacokinetics, potential comorbidities of the patient and perioperative thrombotic and bleeding risk. In low bleeding risk and minor procedures, continuing DOACs seems to be safe. Interrupting DOACs in high-risk procedures might be necessary and should be based on the elimination half-life of the drug and renal function of the patient. Further research is needed to better clarify the role of recently developed reversal agents in the perioperative setting and to identify specific laboratory tests to guide the perioperative management of DOACs.

Inclusion of the Mesentery in Ileocolic Resection for Crohn's Disease is Associated With Reduced Surgical Recurrence.

BACKGROUND AND AIMS: Inclusion of the mesentery during resection for colorectal cancer is associated with improved outcomes but has yet to be evaluated in Crohn's disease. This study aimed to determine the rate of surgical recurrence after inclusion of mesentery during ileocolic resection for Crohn's disease. METHODS: Surgical recurrence rates were compared between two cohorts. Cohort A [n = 30] underwent conventional ileocolic resection where the mesentery was divided flush with the intestine. Cohort B [n = 34] underwent resection which included excision of the mesentery. The relationship between mesenteric disease severity and surgical recurrence was determined in a separate cohort [n = 94]. A mesenteric disease activity index was developed to quantify disease severity. This was correlated with the Crohn's disease activity index and the fibrocyte percentage in circulating white cells. RESULTS: Cumulative reoperation rates were 40% and 2.9% in cohorts A and B [P = 0.003], respectively. Surgical technique was an independent determinant of outcome [P = 0.007]. Length of resected intestine was shorter in cohort B, whilst lymph node yield was higher [12.25 ± 13 versus 2.4 ± 2.9, P = 0.002]. Advanced mesenteric disease predicted increased surgical recurrence [Hazard Ratio 4.7, 95% Confidence Interval: 1.71-13.01, P = 0.003]. The mesenteric disease activity index correlated with the mucosal disease activity index [r = 0.76, p < 0.0001] and the Crohn's disease activity index [r = 0.70, p < 0.0001]. The mesenteric disease activity index was significantly worse in smokers and correlated with increases in circulating fibrocytes. CONCLUSIONS: Inclusion of mesentery in ileocolic resection for Crohn's disease is associated with reduced recurrence requiring reoperation.

TRPA1 mediates changes in heart rate variability and cardiac mechanical function in mice exposed to acrolein.

Short-term exposure to ambient air pollution is linked with adverse cardiovascular effects. While previous research focused primarily on particulate matter-induced responses, gaseous air pollutants also contribute to cause short-term cardiovascular effects. Mechanisms underlying such effects have not been adequately described, however the immediate nature of the response suggests involvement of irritant neural activation and downstream autonomic dysfunction. Thus, this study examines the role of TRPA1, an irritant sensory receptor found in the airways, in the cardiac response of mice to acrolein and ozone. Conscious unrestrained wild-type C57BL/6 (WT) and TRPA1 knockout (KO) mice implanted with radiotelemeters were exposed once to 3ppm acrolein, 0.3ppm ozone, or filtered air. Heart rate (HR) and electrocardiogram (ECG) were recorded continuously before, during and after exposure. Analysis of ECG morphology, incidence of arrhythmia and heart rate variability (HRV) were performed. Cardiac mechanical function was assessed using a Langendorff perfusion preparation 24h post-exposure. Acrolein exposure increased HRV independent of HR, as well as incidence of arrhythmia. Acrolein also increased left ventricular developed pressure in WT mice at 24h post-exposure. Ozone did not produce any changes in cardiac function. Neither gas produced ECG effects, changes in HRV, arrhythmogenesis, or mechanical function in KO mice. These data demonstrate that a single exposure to acrolein causes cardiac dysfunction through TRPA1 activation and autonomic imbalance characterized by a shift toward parasympathetic modulation. Furthermore, it is clear from the lack of ozone effects that although gaseous irritants are capable of eliciting immediate cardiac changes, gas concentration and properties play important roles.

Cancer arising from the remnant mucosa of the ileoanal anastomosis leading to pouchectomy.

Ileal pouch-related adenocarcinoma remains a rarity; thus, guidelines on treatment are currently lacking. We present this case of a 54-year-old man who underwent restorative proctocolectomy with stapled ileal pouch-anal anastomosis formation for familial adenomatous polyposis during the 1980s. Despite undergoing annual surveillance endoscopy, the patient was noted to be anaemic and passing fresh blood per anus Endoscopy and radiological investigation revealed the presence of a pouch-related adenocarcinoma. This was subsequently treated with short-course radiotherapy and pouch excision. The patient remains well until now and will follow six-monthly surveillance protocols with a transition to annual surveillance after 2 years.

Morning NO2 exposure sensitizes hypertensive rats to the cardiovascular effects of same day O3 exposure in the afternoon.

CONTEXT: Within urban air sheds, specific ambient air pollutants typically peak at predictable times throughout the day. For example, in environments dominated by mobile sources, peak nitrogen dioxide (NO2) levels coincide with morning and afternoon rush hours, while peak levels of ozone (O3), occur in the afternoon. OBJECTIVE: Given that exposure to a single pollutant might sensitize the cardiopulmonary system to the effects of a subsequent exposure to a second pollutant, we hypothesized that a morning exposure to NO2 will exaggerate the cardiovascular effects of an afternoon O3 exposure in rats. MATERIALS AND METHODS: Rats were divided into four groups that were each exposed for 3 h in the morning (m) and 3 h in the afternoon (a) on the same day: (1) m-Air/a-Air, (2) m-Air/a-O3 (0.3 ppm), (3) m-NO2 (0.5 ppm)/a-Air and (4) m-NO2/a-O3. Implanted telemetry devices recorded blood pressure and electrocardiographic data. Sensitivity to the arrhythmogenic agent aconitine was measured in a separate cohort. RESULTS: Only m-NO2/a-O3-exposed rats had significant changes in electrophysiological, mechanical and autonomic parameters. These included decreased heart rate and increased PR and QTc intervals and increased heart rate variability, suggesting increased parasympathetic tone. In addition, only m-NO2/a-O3 exposure decreased systolic and diastolic blood pressures and increased pulse pressure and QA interval, suggesting decreased cardiac contractility. DISCUSSION AND CONCLUSION: The findings indicate that initial exposure to NO2 sensitized rats to the cardiovascular effects of O3 and may provide insight into the epidemiological data linking adverse cardiovascular outcomes with exposures to low concentrations of O3.

An appraisal of the computed axial tomographic appearance of the human mesentery based on mesenteric contiguity from the duodenojejunal flexure to the mesorectal level.

OBJECTIVE: The human mesentery is now regarded as contiguous from the duodenojejunal (DJ) to anorectal level. This interpretation prompts re-appraisal of computed tomography (CT) images of the mesentery. METHODS: A digital model and reference atlas of the mesentery were generated using the full-colour data set of the Visible Human Project (VHP). Seventy one normal abdominal CT images were examined to identify mesenteric regions. CT appearances were correlated with cadaveric and histological appearances at corresponding levels. RESULTS: Ascending, descending and sigmoid mesocolons were identifiable in 75%, 86% and 88% of the CTs, respectively. Flexural contiguity was evident in 66%, 68%, 71% and 80% for the ileocaecal, hepatic, splenic and rectosigmoid flexures, respectively. A posterior mesocolic boundary corresponding to the anterior renal fascia was evident in 40% and 54% of cases on the right and left, respectively. The anterior pararenal space (in front of the boundary) corresponded to the mesocolon. CONCLUSIONS: Using the VHP, a mesenteric digital model and reference atlas were developed. This enabled re-appraisal of CT images of the mesentery, in which contiguous flexural and non-flexural mesenteric regions were repeatedly identifiable. The anterior pararenal space corresponded to the mesocolon. KEY POINTS: The Visible Human Project (VHP) allows direct identification of mesenteric structures. Correlating CT and VHP allows identification of flexural and non-flexural mesenteric components. Radiologic appearance of intraperitoneal structures is assessed, starting from a mesenteric platform.

Health effects of soy-biodiesel emissions: mutagenicity-emission factors.

CONTEXT: Soy biodiesel is the predominant biodiesel fuel used in the USA, but only a few, frequently conflicting studies have examined the potential health effects of its emissions. OBJECTIVE: We combusted petroleum diesel (B0) and fuels with increasing percentages of soy methyl esters (B20, B50 and B100) and determined the mutagenicity-emission factors expressed as revertants/megajoule of thermal energy consumed (rev/MJ(th)). MATERIALS AND METHODS: We combusted each fuel in replicate in a small (4.3-kW) diesel engine without emission controls at a constant load, extracted organics from the particles with dichloromethane, determined the percentage of extractable organic material (EOM), and evaluated these extracts for mutagenicity in 16 strains/S9 combinations of Salmonella. RESULTS: Mutagenic potencies of the EOM did not differ significantly between replicate experiments for B0 and B100 but did for B20 and B50. B0 had the highest rev/MJ(th), and those of B20 and B100 were 50% and ∼85% lower, respectively, in strains that detect mutagenicity due to polycyclic aromatic hydrocarbons (PAHs), nitroarenes, aromatic amines or oxidative mutagens. For all strains, the rev/MJ(th) decreased with increasing biodiesel in the fuel. The emission factor for the 16 EPA Priority PAHs correlated strongly (r(2 )= 0.69) with the mutagenicity-emission factor in strain TA100 + S9, which detects PAHs. CONCLUSIONS: Under a constant load, soy-biodiesel emissions were 50-85% less mutagenic than those of petroleum diesel. Without additional emission controls, petroleum and biodiesel fuels had mutagenicity-emission factors between those of large utility-scale combustors (e.g. natural gas, coal, or oil) and inefficient open-burning (e.g. residential wood fireplaces).

Comparative effectiveness of adrenal sparing radical nephrectomy and non-adrenal sparing radical nephrectomy in clear cell renal cell carcinoma: Observational study of survival outcomes.

INTRODUCTION: We compare the survival outcomes of patients with clear cell renal cell carcinoma (RCC) treated with adrenal sparing radical nephrectomy (ASRN) and non-adrenal sparing radical nephrectomy (NASRN). METHODS: We conducted an observational study based on a composite patient population from two university teaching hospitals who underwent RN for RCC between January 2000 and December 2012. Only patients with pathologically confirmed RCC were included. We excluded patients undergoing cytoreductive nephrectomy, with loco-regional lymph node involvement. In total, 579 patients (ASRN = 380 and NASRN = 199) met our study criteria. Patients were categorized by risk groups (all stage, early stage and locally advanced RCC). Overall survival (OS) and cancer-specific survival (CSS) were analyzed for risk groups. Survival analysis was performed using Kaplan-Meier curves and Cox proportional hazards regression. RESULTS: The median follow-up was 41 months (range: 12-157). There were significant benefits in OS (ASRN 79.5% vs. NASRN 63.3%; p = 0.001) and CSS (84.3% vs. 74.9%; p = 0.001), with any differences favouring ASRN in all stage. On multivariate analysis, there was a trend towards worse OS (hazard ratio [HR] 1.759, 95% confidence interval [CI] 0.943-2.309, p = 0.089) and CSS (HR 1.797, 95% CI 0.967-3.337, p = 0.064) in patients with NASRN (although not statistically significant). Of these patients, only 11 (1.9%) had adrenal involvement. CONCLUSIONS: The inherent limitations in our study include the impracticality of conducting a prospective randomized trial in this scenario. Our observational study with a 13-year follow-up suggests ASRN leads to better survival than NASRN. ASRN should be considered the gold standard in treating patients with RCC, unless it is contraindicated.

Mesenteric-Based Surgery Exploits Gastrointestinal, Peritoneal, Mesenteric and Fascial Continuity from Duodenojejunal Flexure to the Anorectal Junction--A Review.

INTRODUCTION: It is now well established that mesenteric-based colorectal surgery is associated with superior outcomes. Recent anatomic observations have demonstrated that the mesenteric organ is contiguous from the duodenojejunal to the anorectal junction. This led to similar observations in relation to associated peritoneum and fascia. The aim of this review was to demonstrate the relevance of the contiguity principle to resectional colorectal surgery. METHODS: All literature in relation to mesenteric anatomy was reviewed from 1873 to the present, without language restriction. RESULTS: Mesenteric-based surgery (i.e. complete mesocolic excision, total mesocolic and mesorectal excision) requires division of the peritoneal reflection (i.e. peritonotomy), and mesenteric mobilisation in the mesofascial plane. These are the fundamental technical elements of mesenterectomy. Mesenteric, peritoneal and fascial contiguity mean that in resectional surgery, these technical elements can be reproducibly applied at all levels from the origin at the superior mesenteric root, to the anorectal junction. CONCLUSIONS: The goals of complete mesocolic, total mesocolic and mesorectal excision can be universally achieved at any level from duodenojejunal flexure to anorectal junction, by adopting technical elements based on mesenteric, peritoneal and fascial contiguity.

Cardiac effects of seasonal ambient particulate matter and ozone co-exposure in rats.

BACKGROUND: The potential for seasonal differences in the physicochemical characteristics of ambient particulate matter (PM) to modify interactive effects with gaseous pollutants has not been thoroughly examined. The purpose of this study was to compare cardiac responses in conscious hypertensive rats co-exposed to concentrated ambient particulates (CAPs) and ozone (O3) in Durham, NC during the summer and winter, and to analyze responses based on particle mass and chemistry. METHODS: Rats were exposed once for 4 hrs by whole-body inhalation to fine CAPs alone (target concentration: 150 µg/m3), O3 (0.2 ppm) alone, CAPs plus O3, or filtered air during summer 2011 and winter 2012. Telemetered electrocardiographic (ECG) data from implanted biosensors were analyzed for heart rate (HR), ECG parameters, heart rate variability (HRV), and spontaneous arrhythmia. The sensitivity to triggering of arrhythmia was measured in a separate cohort one day after exposure using intravenously administered aconitine. PM elemental composition and organic and elemental carbon fractions were analyzed by high-resolution inductively coupled plasma-mass spectrometry and thermo-optical pyrolytic vaporization, respectively. Particulate sources were inferred from elemental analysis using a chemical mass balance model. RESULTS: Seasonal differences in CAPs composition were most evident in particle mass concentrations (summer, 171 µg/m3; winter, 85 µg/m3), size (summer, 324 nm; winter, 125 nm), organic:elemental carbon ratios (summer, 16.6; winter, 9.7), and sulfate levels (summer, 49.1 µg/m3; winter, 16.8 µg/m3). Enrichment of metals in winter PM resulted in equivalent summer and winter metal exposure concentrations. Source apportionment analysis showed enrichment for anthropogenic and marine salt sources during winter exposures compared to summer exposures, although only 4% of the total PM mass was attributed to marine salt sources. Single pollutant cardiovascular effects with CAPs and O3 were present during both summer and winter exposures, with evidence for unique effects of co-exposures and associated changes in autonomic tone. CONCLUSIONS: These findings provide evidence for a pronounced effect of season on PM mass, size, composition, and contributing sources, and exposure-induced cardiovascular responses. Although there was inconsistency in biological responses, some cardiovascular responses were evident only in the co-exposure group during both seasons despite variability in PM physicochemical composition. These findings suggest that a single ambient PM metric alone is not sufficient to predict potential for interactive health effects with other air pollutants.

On-table urethral catheterisation during laparoscopic appendicectomy: Is it necessary?

INTRODUCTION: Laparoscopic appendicectomy (LA) is the most commonly performed surgical emergency procedure. The aim of this study was to highlight a series of iatrogenic bladder injuries during LA and suggest a simple method of prevention. METHODS: A retrospective review was carried out of all LA performed in a university teaching hospital over a two year period 2012-2013. Iatrogenic visceral injuries were identified and operative notes examined. RESULTS: During the study period 1124 appendicectomies were performed. Four iatrogenic bladder injuries occurred related to secondary trocar insertion. No patient was catheterised preoperatively. One of the injuries was identified intra-operatively, another in the early postoperative period where as two re-presented acutely unwell post-discharge from hospital. Three were repaired by laparotomy and one laparoscopically. CONCLUSION: Iatrogenic secondary trocar induced bladder injuries are a rare but preventable and potentially serious complication of LA. Urethral catheterisation during LA is a safe and simple method which can prevent this complication.

Ozone co-exposure modifies cardiac responses to fine and ultrafine ambient particulate matter in mice: concordance of electrocardiogram and mechanical responses.

BACKGROUND: Studies have shown a relationship between air pollution and increased risk of cardiovascular morbidity and mortality. Due to the complexity of ambient air pollution composition, recent studies have examined the effects of co-exposure, particularly particulate matter (PM) and gas, to determine whether pollutant interactions alter (e.g. synergistically, antagonistically) the health response. This study examines the independent effects of fine (FCAPs) and ultrafine (UFCAPs) concentrated ambient particles on cardiac function, and determine the impact of ozone (O3) co-exposure on the response. We hypothesized that UFCAPs would cause greater decrement in mechanical function and electrical dysfunction than FCAPs, and that O3 co-exposure would enhance the effects of both particle-types. METHODS: Conscious/unrestrained radiotelemetered mice were exposed once whole-body to either 190 µg/m³ FCAPs or 140 µg/m³ UFCAPs with/without 0.3 ppm O3; separate groups were exposed to either filtered air (FA) or O3 alone. Heart rate (HR) and electrocardiogram (ECG) were recorded continuously before, during and after exposure, and cardiac mechanical function was assessed using a Langendorff perfusion preparation 24 hrs post-exposure. RESULTS: FCAPs alone caused a significant decrease in baseline left ventricular developed pressure (LVDP) and contractility, whereas UFCAPs did not; neither FCAPs nor UFCAPs alone caused any ECG changes. O3 co-exposure with FCAPs caused a significant decrease in heart rate variability when compared to FA but also blocked the decrement in cardiac function. On the other hand, O3 co-exposure with UFCAPs significantly increased QRS-interval, QTc and non-conducted P-wave arrhythmias, and decreased LVDP, rate of contractility and relaxation when compared to controls. CONCLUSIONS: These data suggest that particle size and gaseous interactions may play a role in cardiac function decrements one day after exposure. Although FCAPs + O3 only altered autonomic balance, UFCAPs + O3 appeared to be more serious by increasing cardiac arrhythmias and causing mechanical decrements. As such, O3 appears to interact differently with FCAPs and UFCAPs, resulting in varied cardiac changes, which suggests that the cardiovascular effects of particle-gas co-exposures are not simply additive or even generalizable. Additionally, the mode of toxicity underlying this effect may be subtle given none of the exposures described here impaired post-ischemia recovery.

Consistent pulmonary and systemic responses from inhalation of fine concentrated ambient particles: roles of rat strains used and physicochemical properties.

Several studies have reported health effects of concentrated ambient particles (CAP) in rodents and humans; however, toxicity end points in rodents have provided inconsistent results. In 2000 we conducted six 1-day exposure studies where spontaneously hypertensive (SH) rats were exposed to filtered air or CAPs (< or = 2.5 microm, 1,138-1,765 microg/m3) for 4 hr (analyzed 1-3 hr afterward). In seven 2-day exposure studies in 2001, SH and Wistar Kyoto (WKY) rats were exposed to filtered air or CAP (< or = 2.5 microm, 144-2,758 microg/m3) for 4 hr/day times 2 days (analyzed 1 day afterward). Despite consistent and high CAP concentrations in the 1-day exposure studies, no biologic effects were noted. The exposure concentrations varied among the seven 2-day exposure studies. Except in the first study when CAP concentration was highest, lavageable total cells and macrophages decreased and neutrophils increased in WKY rats. SH rats demonstrated a consistent increase of lavage fluid gamma-glutamyltransferase activity and plasma fibrinogen. Inspiratory and expiratory times increased in SH but not in WKY rats. Significant correlations were found between CAP mass (microgram per cubic meter) and sulfate, organic carbon, or zinc. No biologic effects correlated with CAP mass. Despite low chamber mass in the last six of seven 2-day exposure studies, the levels of zinc, copper, and aluminum were enriched severalfold, and organic carbon was increased to some extent when expressed per milligram of CAP. Biologic effects were evident in those six studies. These studies demonstrate a pattern of rat strain-specific pulmonary and systemic effects that are not linked to high mass but appear to be dependent on CAP chemical composition.