The Interplay Between Predation, Competition, and Nutrient Levels Influences the Survival of Escherichia coli in Aquatic Environments.

Nutrient levels, competition from autochthonous microorganisms, and protozoan predation may all influence survival of fecal microorganisms as they transition from the gastrointestinal tract to aquatic habitats. Although Escherichia coli is an important indicator of waterborne pathogens, the effects of environmental stressors on its survival in aquatic environments remain poorly understood. We manipulated organic nutrient, predation, and competition levels in outdoor microcosms containing natural river water, sediments, and microbial populations to determine their relative contribution to E. coli survival. The activities of predator (protozoa) and competitor (indigenous bacteria) populations were inhibited by adding cycloheximide or kanamycin. We developed a statistical model of E. coli density over time that fits with the data under all experimental conditions. Predation and competition had significant negative effects on E. coli survival, while higher nutrient levels increased survival. Among the main effects, predation accounted for the greatest variation (40 %) compared with nutrients (25 %) or competition (15 %). The highest nutrient level mitigated the effect of predation on E. coli survival. Thus, elevated organic nutrients may disproportionately enhance the survival of E. coli, and potentially that of other enteric bacteria, in aquatic habitats.

Reservoir Sedimentation and Upstream Sediment Sources: Perspectives and Future Research Needs on Streambank and Gully Erosion.

The future reliance on water supply and flood control reservoirs across the globe will continue to expand, especially under a variable climate. As the inventory of new potential dam sites is shrinking, construction of additional reservoirs is less likely compared to simultaneous flow and sediment management in existing reservoirs. One aspect of this sediment management is related to the control of upstream sediment sources. However, key research questions remain regarding upstream sediment loading rates. Highlighted in this article are research needs relative to measuring and predicting sediment transport rates and loading due to streambank and gully erosion within a watershed. For example, additional instream sediment transport and reservoir sedimentation rate measurements are needed across a range of watershed conditions, reservoir sizes, and geographical locations. More research is needed to understand the intricate linkage between upland practices and instream response. A need still exists to clarify the benefit of restoration or stabilization of a small reach within a channel system or maturing gully on total watershed sediment load. We need to better understand the intricate interactions between hydrological and erosion processes to improve prediction, location, and timing of streambank erosion and failure and gully formation. Also, improved process-based measurement and prediction techniques are needed that balance data requirements regarding cohesive soil erodibility and stability as compared to simpler topographic indices for gullies or stream classification systems. Such techniques will allow the research community to address the benefit of various conservation and/or stabilization practices at targeted locations within watersheds.

The strength of assortative mating for flowering date and its basis in individual variation in flowering schedule.

Although it has been widely asserted that plants mate assortatively by flowering time, there is virtually no published information on the strength or causes of phenological assortment in natural populations. When strong, assortative mating can accelerate the evolution of plant reproductive phenology through its inflationary effect on genetic variance. We estimated potential assortative mating for flowering date in 31 old-field species in Ontario, Canada. For each species, we constructed a matrix of pairwise mating probabilities from the individual flowering schedules, that is the number of flower deployed on successive dates. The matrix was used to estimate the phenotypic correlation between mates, ρ, for flowering date. We also developed a measure of flowering synchrony within species, S, based upon the eigenstructure of the mating matrix. The mean correlation between pollen recipients and potential donors for flowering date was ρ=0.31 (range: 0.05-0.63). A strong potential for assortative mating was found among species with high variance in flowering date, flowering schedules of short duration and skew towards early flower deployment. Flowering synchrony, S, was negatively correlated with potential assortment (r= -0.49), but we go on to show that although low synchrony is a necessary condition for phenological assortative mating, it may not be sufficient to induce assortment for a given phenological trait. The potential correlation between mates showed no seasonal trend; thus, as climate change imposes selection on phenology through longer growing seasons, spring-flowering species are no more likely to experience an accelerated evolutionary response than summer species.

Formation of Manganese Oxide Coatings onto Sand for Adsorption of Trace Metals from Groundwater.

Manganese oxide (MnO) occurs naturally in soil and has a high affinity for trace metals adsorption. In this work, we quantified the factors (pH; flow rate; use of oxidants such as bleach, HO, and O; initial Mn(II) concentrations; and two types of geologic media) affecting MnO coatings onto Ottawa and aquifer sand using batch and column experiments. The batch experiments consisted of manual and automated titration, and the column experiments mimicked natural MnO adsorption and oxidation cycles as a strategy for in situ adsorption. A Pb solution of 50 mg L was passed through MnO-coated sand at a flow rate of 4 mL min to determine its adsorption capacity. Batch experimental results showed that MnO coatings increased from pH 6 to 8, with maximum MnO coating occurring at pH 8. Regarding MnO coatings, bleach and O were highly effective compared with HO. The Ottawa sand had approximately twice the MnO coating of aquifer sand. The sequential increase in initial Mn(II) concentrations on both sands resulted in incremental buildup of MnO. The automated procedure enhanced MnO coatings by 3.5 times compared with manual batch experiments. Column results showed that MnO coatings were highly dependent on initial Mn(II) and oxidant concentrations, pH, flow rate, number of cycles (h), and the type of geologic media used. Manganese oxide coating exceeded 1700 mg kg for Ottawa sand and 130 mg kg for aquifer sand. The Pb adsorption exceeded 2200 mg kg for the Ottawa sand and 300 mg kg for the aquifer sand.

Emergent insights from the synthesis of conceptual frameworks for biological invasions.

A general understanding of biological invasions will provide insights into fundamental ecological and evolutionary problems and contribute to more efficient and effective prediction, prevention and control of invasions. We review recent papers that have proposed conceptual frameworks for invasion biology. These papers offer important advances and signal a maturation of the field, but a broad synthesis is still lacking. Conceptual frameworks for invasion do not require invocation of unique concepts, but rather should reflect the unifying principles of ecology and evolutionary biology. A conceptual framework should incorporate multicausality, include interactions between causal factors and account for lags between various stages. We emphasize the centrality of demography in invasions, and distinguish between explaining three of the most important characteristics by which we recognize invasions: rapid local population increase, monocultures or community dominance, and range expansion. As a contribution towards developing a conceptual synthesis of invasions based on these criteria, we outline a framework that explicitly incorporates consideration of the fundamental ecological and evolutionary processes involved. The development of a more inclusive and mechanistic conceptual framework for invasion should facilitate quantitative and testable evaluation of causal factors, and can potentially lead to a better understanding of the biology of invasions.

Chlorpyrifos and atrazine removal from runoff by vegetated filter strips: experiments and predictive modeling.

Runoff volume and flow concentration are hydrological factors that limit effectiveness of vegetated filter strips (VFS) in removing pesticides from surface runoff. Empirical equations that predict VFS pesticide effectiveness based solely on physical characteristics are insufficient on the event scale because they do not completely account for hydrological processes. This research investigated the effect of drainage area ratio (i.e., the ratio of field area to VFS area) and flow concentration (i.e., uniform versus concentrated flow) on pesticide removal efficiency of a VFS and used these data to provide further field verification of a recently proposed numerical/empirical modeling procedure for predicting removal efficiency under variable flow conditions. Runoff volumes were used to simulate drainage area ratios of 15:1 and 30:1. Flow concentration was investigated based on size of the VFS by applying artificial runoff to 10% of the plot width (i.e., concentrated flow) or the full plot width (i.e., uniform flow). Artificial runoff was metered into 4.6-m long VFS plots for 90 min after a simulated rainfall of 63 mm applied over 2 h. The artificial runoff contained sediment and was dosed with chlorpyrifos and atrazine. Pesticide removal efficiency of VFS for uniform flow conditions (59% infiltration; 88% sediment removal) was 85% for chlorpyrifos and 62% for atrazine. Flow concentration reduced removal efficiencies regardless of drainage area ratio (i.e., 16% infiltration, 31% sediment removal, 21% chlorpyrifos removal, and 12% atrazine removal). Without calibration, the predictive modeling based on the integrated VFSMOD and empirical hydrologic-based pesticide trapping efficiency equation predicted atrazine and chlorpyrifos removal efficiency under uniform and concentrated flow conditions. Consideration for hydrological processes, as opposed to statistical relationships based on buffer physical characteristics, is required to adequately predict VFS pesticide trapping efficiency.

Effectiveness of vegetative filter strips in reducing pesticide loading: quantifying pesticide trapping efficiency.

Pesticide trapping efficiency of vegetated filter strips (VFS) is commonly predicted with low success using empirical equations based solely on physical characteristics such as width and slope. The objective of this research was to develop and evaluate an empirical model with a foundation of VFS hydrological, sedimentological, and chemical specific parameters. The literature was reviewed to pool data from five studies with hypothesized significant parameters: pesticide and soil properties, percent reduction in runoff volume (i.e., infiltration) and sedimentation, and filter strip width. The empirical model was constructed using a phase distribution parameter, defined as the ratio of pesticide mass in dissolved form to pesticide mass sorbed to sediment, along with the percent infiltration, percent sedimentation, and the percent clay content (R(2) = 0.86 and standard deviation of differences [STDD] of 7.8%). Filter strip width was not a statistically significant parameter in the empirical model. For low to moderately sorbing pesticides, the phase distribution factor became statistically insignificant; for highly sorbing pesticides, the phase distribution factor became the most statistically significant parameter. For independent model evaluation datasets, the empirical model based on infiltration and sediment reduction, the phase distribution factor, and the percent clay content (STDD of 14.5%) outperformed existing filter strip width equations (STDD of 38.7%). This research proposed a procedure linking a VFS hydrologic simulation model with the proposed empirical trapping efficiency equation. For datasets with sufficient information for the VFS modeling, the linked numerical and empirical models significantly (R(2) = 0.74) improved predictions of pesticide trapping over empirical equations based solely on physical VFS characteristics.

Wildlife as sentinels of human health effects in the Great Lakes--St. Lawrence basin.

There is no existing formal, long-term program for gathering evidence of the incidence and severity of the health effects of toxic substances in wildlife. However, research-based studies of bald eagles, herring gulls, night herons, tree swallows, snapping turtles, mink, and beluga over the past 30 years have revealed a broad spectrum of health effects in the Great Lakes-St. Lawrence basin including thyroid and other endocrine disorders, metabolic diseases, altered immune function, reproductive impairment, developmental toxicity, genotoxicity, and cancer. These effects occurred most often and were most severe in the most contaminated sites (Green Bay, Saginaw Bay, Lake Ontario, the St. Lawrence estuary, and more recently, Lake Erie), some of which are International Joint Commission-designated Areas of Concern (AOCs). In all cases, a strong argument can be made for an environmental etiology, and in many cases for the involvement of persistent organic pollutants, particularly polychlorinated biphenyls, polychlorinated dibenzo-(italic)p(/italic)-dioxins, and polycyclic aromatic hydrocarbons. For some, the association with particular contaminants is consistent with controlled studies, and in some, dose-response relationships were documented. The biologic significance of these health impairments to the affected species is currently unclear, but they resemble those observed with increased incidence in human subpopulations in one or more AOCs. Formalizing health effects monitoring of sentinel wildlife species by the parties to the Canada-USA Great Lakes Water Quality Agreement is required. This would facilitate the optimal use of sentinel wildlife health data in a larger, epidemiologic weight-of-evidence context upon which to base decisions and policies regarding the effects of chemical exposures on human populations.

Associations between altered immune function and organochlorine contamination in young Caspian terns (Sterna caspia) from Lake Huron, 1997-1999.

Previous studies of laboratory animals and wildlife species have demonstrated the immunotoxicity of organochlorines. This study confirmed that associations between organochlorines and suppressed T cell function and enhanced antibody production in young Caspian terns from the Great Lakes, first observed in the early 1990s, continued into the late 1990s. These associations were based on measurement of organochlorines in plasma of individuals and pooled egg samples. During 1997-99, immune function, hematological variables, and organochlorine contamination were measured in prefledgling Caspian terns at two Lake Huron colonies: Channel Shelter Island (Confined Disposal Facility) at the mouth of the Saginaw River in southern Saginaw Bay and Elm Island in the North Channel. Elevated organochlorine exposure, reproductive effects, and decreased recruitment have been documented previously in the Saginaw Bay colony. Concentrations of polychlorinated biphenyls (PCBs) in eggs and plasma and 1,1-dichloro-2,2-bis(p)chlorophenyl)ethylene (DDE) in plasma were consistently higher in Saginaw Bay compared to the North Channel. The mean phytohemagglutinin (PHA) skin test, a measure of T lymphocyte function, was 42% lower in Saginaw Bay. Regression analyses showed strong negative associations between the PHA response and plasma PCBs and, to a slightly lesser degree, DDE. Despite interyear differences, total antibody titers following immunization with sheep red blood cells were higher in Saginaw Bay than the North Channel. Titers were positively associated with plasma PCBs and DDE. Plasma PCBs and DDE were negatively correlated with the percentage of monocytes and positively correlated with the percentage of basophils.

Induced minisatellite germline mutations in herring gulls (Larus argentatus) living near steel mills.

Despite widespread industrial release of genotoxic contaminants, little is understood of their role in inducing germline mutations in natural populations. We used multilocus DNA fingerprinting to quantify germline minisatellite mutations in families of herring gulls (Larus argentatus) in three nesting categories: (a) near cities with large steel mills operating coking ovens; (b) near cities without steel mills; and (c) in rural locations removed from point sources of contamination. Gulls nesting near integrated steel mills showed significantly higher mutation rates than gulls from rural locations (Fisher's exact, P=0.0004); urban sites without steel mills fell midway between steel and rural sites (difference from rural; Fisher's exact, P=0.19). Distance of the nesting location of herring gulls from the steel industries' coking ovens was negatively correlated with minisatellite mutation rate demonstrating significant risk for induced germline mutations in cities with steel operations (Kendall Tau; tau=0.119; P<0.0001).

Dissociable cognitive impairments in problem drinkers.

Patients in a treatment programme for severe alcohol dependence were tested on a battery of tests designed to examine organizational and visuo-spatial abilities. Analysis using a case-study approach indicated independent organizational and visuo-spatial impairments. An understanding of aetiological factors underlying these cognitive deficits and implications for treatment are discussed.

Geographic variation in hematological variables in adult and prefledgling herring gulls (Larus argentatus) and possible associations with organochlorine exposure.

The objectives of this study were (1) to describe variation in hematological values found in adult and prefledgling herring gulls (Larus argentatus) over a large geographic area, (2) to investigate relationships between hematological variables and other physiological indices, and (3) to examine potential associations between exposure to organochlorines and hematological variables. During 1991-93, we sampled 160 breeding adult gulls from 13 colonies and 101 4-week-old gulls from 11 colonies. All colonies were in the Great Lakes ecosystem, except for two colonies on Lake Winnipeg and the Atlantic coast. The hematological values measured in this study were similar to published values for herring gulls and related species. Significant intersite differences were found in hematological variables. Sex had little or no influence on leukocyte variables. Adults had lower total leukocyte counts and higher heterophil to lymphocyte ratios than chicks. PCV was lower in adult females than males. In adults, total leukocyte and total heterophil numbers were negatively associated with liver activity of ethoxyresorufin-O-deethylase (EROD) and concentrations of highly carboxylated porphyrins (HCPs), two biomarkers of organochlorine exposure. Total leukocyte and total heterophil numbers were positively associated with liver concentrations of DDE (1, 1-dichloro-2,2-bis(p-chlorophenyl)ethylene), and total lymphocytes were associated positively with PCB (polychlorinated biphenyl) and HCP concentrations. The heterophil to lymphocyte ratio was negatively associated with liver EROD activity and HCPs. In chicks, there was a positive association between the heterophil to lymphocyte ratio and HG-TEQs (dioxin toxicity equivalents calculated using herring gull-specific equivalency factors). PCV was associated with some measures of contaminant exposure in adults and chicks. Additional research is needed to elucidate causal relationships between hematological indices and such factors as contaminants, disease, and nutrition.

Geographic variation in blood plasma protein concentrations of young herring gulls (Larus argentatus) and Caspian terns (Sterna caspia) from the Great Lakes and Lake Winnipeg.

Relative and total amounts of plasma protein fractions are affected by infections, inflammation, and nutritional and physiological status, and are therefore important health indicators in free-living animals. Our objectives were: (1) to examine intercolony differences in plasma protein fractions in prefledgling gulls and terns; (2) to investigate relationships between plasma proteins and other physiological measures such as weight loss, growth, and immune function; and (3) to examine potential associations between organochlorine exposure and plasma proteins. During 1992, blood was collected from 3-week-old herring gull (Larus argentatus) chicks from six sites on Lakes Superior, Huron, Michigan, Erie, and Winnipeg and from 3-week-old Caspian tern (Sterna caspia) chicks from five sites on Lakes Huron, Michigan, and Ontario. These sites provided a wide gradient of organochlorine contamination. Plasma proteins were separated by high-resolution agarose gel electrophoresis and stained with Coomassie brilliant blue dye. Six major fractions were quantified: prealbumin, albumin, alpha-globulins, beta(1)-globulins, beta(2)-globulins, and gamma-globulins. Total protein, prealbumin, albumin, and gamma-globulin concentrations and the albumin/globulin ratio did not differ among sites. Total protein, albumin, and the albumin/globulin ratio were not decreased in birds experiencing food stress or weight loss. Intersite differences were found in alpha- and beta-globulins. In gulls, beta(2)-globulins were positively associated with polychlorinated biphenyls (PCBs) and 1,1-dichloro-2,2-bis(p-chlorophenyl)ether (DDE). In terns, PCBs were negatively associated with alpha-globulins and positively associated with beta(1)-globulins. Additional research is needed to identify individual proteins and elucidate causal relationships between the particular protein concentrations and factors such as contaminants, growth, and condition.

Spatial structure, environmental heterogeneity, and population dynamics: analysis of the coupled logistic map.

Spatial extent can have two important consequences for population dynamics: It can generate spatial structure, in which individuals interact more intensely with neighbors than with more distant conspecifics, and it allows for environmental heterogeneity, in which habitat quality varies spatially. Studies of these features are difficult to interpret because the models are complex and sometimes idiosyncratic. Here we analyze one of the simplest possible spatial population models, to understand the mathematical basis for the observed patterns: two patches coupled by dispersal, with dynamics in each patch governed by the logistic map. With suitable choices of parameters, this model can represent spatial structure, environmental heterogeneity, or both in combination. We synthesize previous work and new analyses on this model, with two goals: to provide a comprehensive baseline to aid our understanding of more complex spatial models, and to generate predictions about the effects of spatial structure and environmental heterogeneity on population dynamics. Spatial structure alone can generate positive, negative, or zero spatial correlations between patches when dispersal rates are high, medium, or low relative to the complexity of the local dynamics. It can also lead to quasiperiodicity and hyperchaos, which are not present in the nonspatial model. With density-independent dispersal, spatial structure cannot destabilize equilibria or periodic orbits that would be stable in the absence of space. When densities in the two patches are uncorrelated, the probability that the population in a patch reaches extreme low densities is reduced relative to the same patch in isolation; this "rescue effect" would reduce the probability of metapopulation extinction beyond the simple effect of spreading of risk. Pure environmental heterogeneity always produces positive spatial correlations. The dynamics of the entire population is approximated by a nonspatial model with mean patch characteristics. This approximation worsens as the difference between the patches increases and the dispersal rate decreases: Under extreme conditions, destabilization of equilibria and periodic orbits occurs at mean parameter values lower than those predicted by the mean parameters. Apparent within-patch dynamics are distorted: The local population appears to have the wrong growth parameter and a constant number of immigrants (or emigrants) per generation. Adding environmental heterogeneity to spatial structure increases the occurrence of spatially correlated population dynamics, but the resulting temporal dynamics are more complex than would be predicted by the mean parameter values. The three classes of spatial pattern (positive, negative, and zero correlation), while still mathematically distinct, become increasingly similar phenomenologically.

Coronary artery bypass graft surgery in Newfoundland and Labrador.

BACKGROUND: Newfoundland and Labrador, like other health care jurisdictions, is faced with widening gaps between the demands for health care and a strained ability to supply the necessary resources. The authors carried out a study to determine the rates of appropriate and inappropriate coronary artery bypass grafting (CABG) in the province and the waiting times for this surgery. METHODS: This retrospective cohort study was performed in the tertiary care hospital that receives all referrals for coronary angiography and coronary artery revascularization for Newfoundland and Labrador. By reviewing the hospital records, the authors identified 2 groups of patients: those in whom critical coronary artery disease was diagnosed on the basis of coronary angiography and who were referred for CABG between Apr. 1, 1994, and Mar. 31, 1995, and those who actually underwent the procedure during that period. By applying specific criteria developed by the RAND Corporation, the authors determined the appropriateness and necessity of CABG in each case. They also compared waiting times for CABG with optimal waiting times; as determined by a consensus-based priority score. RESULTS: A total of 338 patients underwent CABG during the study period. The cases were characterized by multivessel disease and late-stage angina symptoms. Almost all of the patients had high appropriateness scores (7-9), and nearly 95% had high necessity scores (7-9). However, during the study period, the waiting list increased by about 20%, because a total of 391 patients were referred by the weekly cardiovascular surgery conference; the authors identified these and an additional 31 patients as having necessity scores of 7 or more. Only 7 (23%) of 31 patients for whom CABG was considered very urgent underwent surgery within the recommended 24 hours, and only 30 (24%) of the 122 patients for whom CABG was considered urgent underwent surgery within the recommended 72 hours. INTERPRETATION: These results provide evidence that the cardiac surgery program in Newfoundland and Labrador is performing CABG in patients for whom surgical revascularization is highly appropriate and necessary. Access to CABG is less than ideal, however, since the waiting list continues to expand, and many patients wait beyond the recommended time for surgery.

Organochlorine-associated immunosuppression in prefledgling Caspian terns and herring gulls from the Great Lakes: an ecoepidemiological study.

The objectives of study were to determine whether contaminant-associated immunosuppression occurs in prefledgling herring gulls and Caspian terns from the Great Lakes and to evaluate immunological biomarkers for monitoring health effects in wild birds. During 1992 to 1994, immunological responses and related variables were measured in prefledgling chicks at colonies distributed across a broad gradient of organochlorine contamination (primarily polychlorinated biphenyls), which was measured in eggs. The phytohemagglutinin skin test was used to assess T-lymphocyte function. In both species, there was a strong exposure-response relationship between organochlorines and suppressed T-cell-mediated immunity. Suppression was most severe (30-45%) in colonies in Lake Ontario (1992) and Saginaw Bay (1992-1994) for both species and in western Lake Erie (1992) for herring gulls. Both species exhibited biologically significant differences among sites in anti-sheep red blood cells antibody titers, but consistent exposure-response relationships with organochlorines were not observed. In Caspian terns and, to a lesser degree, in herring gulls, there was an exposure-response relationship between organochlorines and reduced plasma retinol (vitamin A). In 1992, altered White blood cell numbers were associated with elevated organochlorine concentrations in Caspian terns but not herring gulls. The immunological and hematological biomarkers used in this study revealed contaminant-associated health effects in wild birds. An epidemiological analysis strongly supported the hypothesis that suppression of T-cell-mediated immunity was associated with high perinatal exposure to persistent organochlorine contaminants.

Circulatory sequelae of administering CPAP in hyperdynamic sepsis are time dependent.

Evidence questions the circulation's ability to acutely compensate for abrupt changes in O2 delivery (Qo2). Because both sepsis and continuous positive airway pressure (CPAP) may alter the metabolic regulation of tissue oxygenation, we designed an experiment to determine the interaction, if any, between sepsis and time on circulatory homeostasis after the application of CPAP. Twenty-four sheep were randomized to cecal ligation and perforation (CLP) or sham procedure (Sham) and then rerandomized to receive either CPAP (10 mmHg) or no CPAP (No CPAP; CLP/CPAP, n = 8; CLP/No CPAP, n = 8; Sham/CPAP, n = 4; Sham/No CPAP, n = 4). Forty-eight hours later, CLP animals demonstrated an elevated cardiac index (+63%), systemic Qo2 (+49%), and systemic O2 uptake (+28%). Organ blood flow, measured with radiolabeled microspheres, was augmented to the heart and depressed in organs comprising the splanchnic circulation. Compared with the CLP/No CPAP group and both Sham groups, myocardial Qo2 in the CLP/ CPAP group was significantly elevated when measured both 2 and 8 h after CPAP. These changes were unrelated to differences in mean heart work between the study groups. Simultaneously, QO2 to all of the small gut, large gut, pancreas, and kidney in the CLP/CPAP group was elevated during the 2-h study yet reverted to levels not different from baseline by the 8-h study. These data demonstrate 1) a unique sepsis x time interaction with the use of 10 mmHg of CPAP, particularly in the "nonvital" circulations, and 2) CPAP effects on the septic coronary circulation, which were unexplained by changes in external determinants of myocardial O2 need.

Cyclooxygenase inhibition and vascular reactivity in a rat model of hyperdynamic sepsis.

We postulated that the attenuated pulmonary and systemic vascular contractility observed in sepsis was secondary to the release of vasodilator prostaglandins. We used the cyclooxygenase inhibitor meclofenamate to inhibit prostaglandin synthesis in an unanesthetized, chronically instrumented model of hyperdynamic sepsis. Sixteen male Sprague-Dawley rats (300-350 g) were randomized to either sepsis induced by cecal ligation and perforation (CLP, n = 8) or a sham procedure (Sham, n = 8). Vascular reactivity was assessed by measuring the hypoxic (FiO2 = 0.08) pulmonary pressor response (HPV), and the systemic pressor response to an intravenous infusion of phenylephrine (1.5-7.5 micrograms/kg/min) before and after the administration of meclofenamate (5 mg/kg intravenously, i.v.). Twenty-four hours postoperatively, CLP animals had significantly increased cardiac output (CO) as compared with Sham animals (204 +/- 12 vs. 148 +/- 5 ml/min, p < 0.05), slightly decreased mean arterial pressure (MAP) (109 +/- 4 vs. 118 +/- 3 mm Hg, p < 0.05), and decreased total systemic vascular resistance (TSVR) (0.546 +/- 0.046 vs. 0.805 +/- 0.030 mm Hg.min.ml-1, p < 0.05). Mean pulmonary artery pressure (MPAP) and total pulmonary vascular resistance (TPVR) were similar in both groups (p > 0.05). In response to hypoxia, the change in MPAP (delta MPAP) was 3.6 +/- 1.0 and 6.9 +/- 0.8 (mm Hg) in CLP and Sham animals, respectively (p < 0.05). Similarly, the change in TPVR (delta TPVR) during hypoxia was 0.012 +/- 0.006 and 0.038 +/- 0.009 mm Hg.min.ml-1 in CLP and Sham (p < 0.05). The pulmonary and systemic blood pressure (BP) response to phenylephrine was also attenuated in CLP as compared with Sham animals. After treatment with meclofenamate, differences were no longer apparent in the HPV response between CLP and Sham animals, due to a slight increase in the HPV response of CLP animals and a slight decrease in the HPV response in Sham animals. The attenuated pressor response to phenylephrine was not changed in either the pulmonary or the systemic circulation after the administration of meclofenamate. These data suggest that vasodilator prostaglandins may contribute to the attenuated pulmonary pressor response in sepsis. However, the mechanism of the attenuated HPV may be different than the attenuated response to exogenous catecholamines since meclofenamate had no effect on either the pulmonary or systemic response to a phenylephrine infusion in septic animals.

Calcitonin gene-related peptide does not mediate the abnormal vascular reactivity observed in a rat model of acute Pseudomonas pneumonia.

Abnormal systemic and pulmonary vascular reactivity has been demonstrated in numerous models of sepsis and pneumonia. Furthermore, the attenuated hypoxic pulmonary pressor response observed in these animals probably is responsible for the ventilation/perfusion (V/Q) mismatching and consequent arterial hypoxemia. We hypothesized that excess release of endogenous vasodilators such as calcitonin gene-related peptide (CGRP) in pneumonia was responsible for the diminished hypoxic pressor response. Using the CGRP receptor antagonist CGRP (8-37), we examined the role of CGRP in the attenuated hypoxic pulmonary response in a rat model of acute Pseudomonas pneumonia. Sixteen Sprague-Dawley rats were instrumented for chronic hemodynamic monitoring and subsequently randomized to either Pneumonia (n = 8), induced by the instillation of 0.2 ml broth containing 2 x 10(8) colony-forming units (CFU)/ml Pseudomonas aeruginosa into the right lower lobe, or Sham (n = 8) procedure. Hemodynamic measurements and the hypoxic (FiO2 = 0.08) pulmonary pressor response were recorded at baseline, 48 h after the pneumonia or sham procedure and after the administration of 250 micrograms CGRP (8-37) (post-CGRP(8-37)). The regional distribution of pulmonary blood flow was determined by the injection of radioactive microspheres. Forty-eight hours after the instillation of Pseudomonas, Pneumonia animals had significantly increased cardiac output (CO) as compared with Sham (193 +/- 7 vs. 154 +/- 7 ml/min, p < 0.05), slightly decreased mean arterial pressure (MAP 109 +/- 4 vs. 118 +/- 3 mm Hg, p = NS), and reduced total systemic vascular resistance (TSVR 0.57 +/- 0.03 vs. 0.78 +/- 0.05 mm Hg.min.ml-1, p < 0.05). Pneumonia animals were further characterized by increased mean pulmonary artery pressure (MPAP) as compared with Sham (24 +/- 2 vs. 20 +/- 1 mm Hg, p < 0.05) animals, and an increased alveolar-arterial (A-a) oxygen gradient (31 +/- 3 vs. 20 +/- 4 mm Hg, p < 0.05). The administration of CGRP (8-37) did not alter baseline hemodynamic variables and did not change the pressor response to hypoxia in either group. Furthermore, CGRP receptor blockade did not alter the distribution of blood flow in the lung during normoxia or hypoxia. These data suggest that although this model of acute pneumonia is characterized by an attenuated hypoxic pressor response, the mechanism does not appear to be mediated by excess release of the vasodilator CGRP.