Food web structure of fish communities of Doce River, 5 years after the Fundão dam failure.

The rupture of the Fundão dam is considered the largest mining failure in history, which had a particularly detrimental impact on fish populations, as the mud from the ore tailings significantly altered the water quality and habitat of Doce River basin. This study aimed to assess the trophic structure of fish communities in areas impacted and not impacted by the dam rupture in the Doce River basin. To evaluate the food web structure, community-wide trophic niche, and trophic positions of fish, stable isotopes of carbon (δ13C) and nitrogen (δ15N) were utilized across ten sites (seven impacted and three control). In general, fish appeared to assimilate resources such as invertebrates, algae, and periphyton, although the importance of each resource varied among sites. The site closest to the dam rupture exhibited a more simplified trophic structure compared to the control sites and those nearer the river mouth. In this site, most fish species occupied a similar trophic position. Trophic niches also exhibited the greatest dissimilarity between the site closest to the dam failure and those farther away from it, with an expansion of trophic niche breadth observed with an increase in the distance from the dam rupture. Our study provided valuable insights into the trophic structure of fish communities within the Doce River basin, shedding light on the trophic ecology of the 59 fish species investigated. We also emphasize the importance of our study for future assessments of ore tailings dam failure disasters and evaluating the effectiveness of mitigation measures for Doce River basin recovery.

Ecosystem variables importance in the presence and abundance of a globally invasive fish.

Changes in physical habitat that are associated with anthropogenic disturbances facilitate the establishment and expansion of non-native species in receiving environments. Here, we evaluated the relative importance of ecosystem variables for the presence and abundance of the invasive fish Poecilia reticulata in Brazil. We collected fish species and assessed environmental variables through an established physical habitat protocol in 220 stream sites located in southeastern and midwestern Brazil. A total of 14,816 P. reticulata individuals were collected in 43 stream sites, and 258 variables that describe the physical characteristics of streams were assessed, including measures of channel morphology, substrate size and type, habitat complexity and cover, riparian vegetation cover and structure, and human influence. Dimensionality reduction methods were employed to limit redundancy, resulting in a smaller set of the most relevant environmental variables. Subsequently, we used random forest models to assess the relative importance of these variables in determining the presence and abundance of P. reticulata. The presence of this invasive fish was primarily explained by human disturbance variables related to urbanization (total impact, pavement, artificial structure areal cover, riparian canopy cover, electrical conductivity, mean thalweg depth, and sand), whereas channel morphology (mean bank full height) and fish cover variables (natural fish cover, and aquatic macrophyte areal cover) were important predictors of its abundance. Identifying which ecosystem variables are favorable to the establishment of non-native species is an important step in preventing future biological invasions, as well as managing those that already occur.

Automation of a tertiary hospital pharmacy drug dispensing system in a lower-middle-income country: A case study and preliminary results.

Background: An increase in the use of automated systems has optimised the drug dispensing process in hospitals. Methods: This case study describes the implementation of automated drug dispensing system and presents the preliminary results of automated pharmaceutical dispensing with robots (PillPick® and BoxPicker®, ©Swisslog Healthcare) at Hospital Sírio-Libanês, a private tertiary hospital in Brazil. Results: During the study period, between 2013 (pre-automation) and 2017 (post-automation) the number total of medication errors has not changed post-automation, but there was significant reduction in error in the dispensing phase with a relative risk of 0.84 (95% confidence interval: 0.70-0.99) withal a reduction in the numbers of returned items, breakages, and loss of medications, although that delivery times have increased.. Conclusion: The study results suggest that the use of robotic systems in the central pharmacy may improve hospital pharmacy management and generate only a few errors in dispensing pharmaceuticals.

Nitrogen pollution promotes changes in the niche space of fish communities.

Historically, anthropogenic fixed nitrogen has been purposely increased to benefit food production and global development. One consequence of this increase has been to raise concentrations of nitrogen in aquatic ecosystems. To evaluate whether nitrogen pollution promotes changes in the estimates of niche space of fish communities, we examined 16 sites along a Brazilian river basin highly impacted by anthropogenic activities, especially discharge of domestic and industrial sewage from a region with more than 5 million inhabitants. We analysed the carbon (δ13C) and nitrogen (δ15N) isotope ratios of fish species and both autochthonous (periphyton) and allochthonous (course and fine particulate organic matter) basal food resources. To estimate the magnitude of nitrogen pollution, we measured the nitrate and ammonium concentrations at each site. Sampling was conducted in the dry and wet seasons to evaluate the influence of seasonality. Nitrogen pollution generally increased estimates of niche space, and seasonality influenced only the niche estimates of fish communities from polluted sites. In addition, isotopic analyses of nitrogen polluted sites yielded unrealistic estimates of trophic positioning (detritivores at the top of the food web). We conclude that changes in niche space estimates reflect both alterations in baseline isotopic values and differential trophic behaviour among fishes. Our study suggests that under conditions of high pollution, other factors appear to influence isotopic estimates of niche, such as isotopically distinct sources that have not been sampled, and/or differences in δ15N turnover rates between fish tissue and basal resources, creating isotopic baselines that are challenging to interpret.

The impact of chronic obstructive pulmonary disease in patients' lives: The perception of the health professionals.

INTRODUCTION: The perception of health professionals about chronic obstructive pulmonary disease (COPD) has not been thoroughly investigated. OBJECTIVE: To analyze the perception of health professionals about the impact of COPD on the lives of affected individuals. MATERIALS AND METHODS: Qualitative and cross-sectional study with five health professionals: two nurses, two physiotherapists, and one medical doctor. They participated in a focus group (FG) session, with semistructured questions covering: definition of COPD, activities of daily living (ADL), and physical activity of daily living (PADL), as well as the importance of these outcomes in the lives of individuals with COPD. DATA ANALYSIS: The FG was recorded, transcribed, and analyzed according to the content analysis. RESULTS: The FG highlighted four main themes: physical-functional and emotional impairment of individuals, the importance of patient-health professional contact, repercussions of COPD on the patients' physical activity, and strategies for promoting physical activity. Based on the four themes exposed, the health professionals reported that there is a progression in the lives of individuals' with COPD, which is divided into three phases: adaptation, reluctance, and dependence. CONCLUSION: There was a negative perception of the health professionals regarding the functionality and emotion of patients with COPD. Emotional aspects, family support, and architectural structure can positively or negatively influence patients' ADL and PADL. Finally, there was a perception of progression in the life of patients with COPD, since their initial adaptation, evolving to physical and emotional dependence.

Trophic diversity and carbon sources supporting fish communities along a pollution gradient in a tropical river.

Anthropogenic activities can have a great influence on water quality and in the availability of habitat and food resources, which can promote changes in the trophic diversity and carbon sources sustaining aquatic communities. The objective of this study was to evaluate if the trophic diversity and the main carbon sources sustaining fish communities change along a pollution gradient. The study was carried out at eight sites distributed along the Rio das Velhas, a Brazilian river highly impacted by anthropogenic activities, in which the discharge of domestic and industrial sewage from the Metropolitan Region of Belo Horizonte (MRBH) presents a major source of pollution. Using carbon (δ13C) and nitrogen (δ15N) isotope ratios, we identified the major carbon sources/food sources of common fish species and calculated six metrics of trophic diversity. Autochthonous primary producers (algae, periphyton, and macrophytes) were the main carbon sources for all trophic guilds at all sites, but notably, sewage-derived organic matter was an additional significant carbon source to the fish community in the most polluted testing site. Here, the community was composed mainly by detritivorous and omnivorous fishes and exhibited greater ranges of carbon and nitrogen isotopic values, large total areas, high trophic diversity, small trophic redundancy, and less even distribution of trophic niches than the less polluted sites. We conclude that the trophic guilds, trophic diversity metrics, and carbon sources sustaining fish communities in the Rio das Velhas are highly influenced by the presence of pollution. Besides favoring omnivorous and detritivorous fishes, the input of sewage also provided an important food source to sustain the fish community from sites close to the MRBH.

Effects of land- and water-based exercise programmes on postural balance in individuals with COPD: additional results from a randomised clinical trial.

OBJECTIVE: To investigate the effects of water-based exercise training on postural balance in individuals with chronic obstructive pulmonary disease (COPD), and compare the effects of two similar protocols of land- and water-based exercise programmes on postural balance in this population. DESIGN: Randomised clinical trial. SETTING: University-based, outpatient, physical therapy clinic. SUBJECTS: Fifty individuals with COPD. INTERVENTIONS: Participants were assigned at random to the land group (LG; n=27) or the water group (WG; n=23), and underwent high-intensity endurance and strength training three times per week for 3months. MAIN OUTCOME MEASURES: Functional balance was assessed by the timed up and go test (TUG), and static balance was assessed with a force platform in the following conditions: standing with feet hip-width apart and eyes open; standing with feet hip-width apart and eyes closed; standing on a short base; and one-legged stance. RESULTS: Seventeen subjects completed the intervention in the LG {nine males, mean age 64 [standard deviation (SD) 8] years, mean forced expiratory volume in 1 second (FEV1) 48 (SD 17) %predicted} compared with 14 subjects in the WG [nine males, mean age 65 (SD 8) years, FEV1 51 (SD 15) %predicted]. Water-based exercise training had a positive effect on functional balance [TUG: mean difference -1.17 (-1.93 to -0.41 95% confidence interval) seconds; P=0.006], whereas static balance remained unaltered for both groups. There was no between-group difference in postural balance after exercise training; however, a higher proportion of participants who had a clinically relevant improvement in the TUG were in the WG (LG 35%, WG 64%; P<0.001). CONCLUSION: Functional balance improved after 3months of high-intensity exercise training performed in water. Despite the environment, non-specific training seems to be insufficient to improve static balance. CLINICAL TRIAL REGISTRATION NUMBER: clinicalTrials.gov NCT01691131.

Trophic responses to aquatic pollution of native and exotic livebearer fishes.

The objective of this study was to evaluate if aquatic pollution promote diet shifts in two livebearer fishes (Poeciliidae): an exotic species, the guppy (Poecilia reticulata), and a native livebearer (Phalloceros uai). The study was carried out in a Brazilian basin highly impacted by anthropogenic activities, especially discharge of domestic and industrial sewage from a region with more than five million human inhabitants. To evaluate the trophic ecology of both native and exotic species it was analysed carbon (δ13C) and nitrogen (δ15N) stable isotopes of fish tissue, food resources and, sewage. Moreover, stable isotopes analyses were coupled with gut contents of the two species to provide additional information about fish diet. Exotic guppy abundance was high in the most polluted site, where P. reticulata assimilated carbon directly from sewage. The native species was absent in the most polluted site, but presented wider niches than the exotic species in almost all other sites. Gut content analyses indicated high consumption of aquatic insects by both species. However, while the native species consumed a diverse suite of insect taxa, the exotic species consumed mainly Chironomidae larvae. We conclude that aquatic pollution promotes diet shifts in both native and exotic species, with both species changing their trophic niches in a similar way according to the level of degradation of the environment. The ability to directly assimilate sewage, together with its capacity to survive in environments with poor water quality and its reproductive strategy, may favour the establishment of exotic guppies in strongly polluted sites.

Impact assessment of an automated drug-dispensing system in a tertiary hospital.

OBJECTIVE: To evaluate the costs and patient safety of a pilot implementation of an automated dispensing cabinet in a critical care unit of a private tertiary hospital in São Paulo/Brazil. METHODS: This study considered pre- (January-August 2013) and post- (October 2013-October 2014) intervention periods. We considered the time and cost of personnel, number of adverse events, audit adjustments to patient bills, and urgent requests and returns of medications to the central pharmacy. Costs were evaluated based on a 5-year analytical horizon and are reported in Brazilian Reals (R$) and US dollars (USD). RESULTS: The observed decrease in the mean number of events reported with regard to the automated drug-dispensing system between pre- and post-implementation periods was not significant. Importantly, the numbers are small, which limits the power of the mean comparative analysis between the two periods. A reduction in work time was observed among the nurses and administrative assistants, whereas pharmacist assistants showed an increased work load that resulted in an overall 6.5 hours of work saved/day and a reduction of R$ 33,598 (USD 14,444) during the first year. The initial investment (R$ 206,065; USD 88,592) would have been paid off in 5 years considering only personnel savings. Other findings included significant reductions of audit adjustments to patient hospital bills and urgent requests and returns of medications to the central pharmacy. CONCLUSIONS: Evidence of the positive impact of this technology on personnel time and costs and on other outcomes of interest is important for decision making by health managers.

Impact assessment of an automated drug-dispensing system in a tertiary hospital

OBJECTIVE: To evaluate the costs and patient safety of a pilot implementation of an automated dispensing cabinet in a critical care unit of a private tertiary hospital in São Paulo/Brazil. METHODS: This study considered pre- (January-August 2013) and post- (October 2013-October 2014) intervention periods. We considered the time and cost of personnel, number of adverse events, audit adjustments to patient bills, and urgent requests and returns of medications to the central pharmacy. Costs were evaluated based on a 5-year analytical horizon and are reported in Brazilian Reals (R$) and US dollars (USD). RESULTS: The observed decrease in the mean number of events reported with regard to the automated drug-dispensing system between pre- and post-implementation periods was not significant. Importantly, the numbers are small, which limits the power of the mean comparative analysis between the two periods. A reduction in work time was observed among the nurses and administrative assistants, whereas pharmacist assistants showed an increased work load that resulted in an overall 6.5 hours of work saved/day and a reduction of R$ 33,598 (USD 14,444) during the first year. The initial investment (R$ 206,065; USD 88,592) would have been paid off in 5 years considering only personnel savings. Other findings included significant reductions of audit adjustments to patient hospital bills and urgent requests and returns of medications to the central pharmacy. CONCLUSIONS: Evidence of the positive impact of this technology on personnel time and costs and on other outcomes of interest is important for decision making by health managers.

Participation of locus coeruleus in breathing control in female rats.

Several evidences indicate that the locus coeruleus (LC) is involved in central chemoreception responding to CO2/pH and displaying a high percentage of chemosensitive neurons (>80%). However, there are no studies about the LC-mediated hypercapnic ventilation performed in females. Therefore, we assessed the role of noradrenergic LC neurons in non-ovariectomized (NOVX), ovariectomized (OVX) and estradiol (E2)-treated ovariectomized (OVX+E2) rats in respiratory response to hypercapnia, using a 6-hydroxydopamine (6-OHDA) - lesion model. A reduction in the number of tyrosine hydroxylase (TH) immunoreactive neurons (51-90% in 3 animals of NOVX group, 20-42% of lesion in 5 animals of NOVX females, 61.3% for OVX and 62.6% for OVX+E2 group) was observed seven days after microinjection of 6-OHDA in the LC. The chemical lesion of the LC resulted in decreased respiratory frequency under normocapnic conditions in OVX and OVX+E2 group. Hypercapnia increased ventilation in all groups as consequence of increases in respiratory frequency (fR) and tidal volume (VT). Nevertheless, the hypercapnic ventilatory response was significantly decreased in 6-OHDA-NOVX>50% rats compared with SHAM-NOVX group and with females that had 20-42% of LC lesion. In OVX and OVX+E2 lesioned groups, no difference in CO2 ventilatory response was observed when compared to SHAM-OVX and SHAM-OVX+E2 groups, respectively. Neither basal body temperature (Tb) nor Tb reduction in response to hypercapnia were affected by E2 treatment, ovariectomy or LC lesion. Thus, our data show that LC noradrenergic neurons seem to exert an excitatory role on the hypercapnic ventilatory response in female rats, as evidenced by the results in NOVX animals with LC lesioned more than 50%; however, this modulation is not observed in OVX and OVX+E2 rats. In addition, LC noradrenergic neurons of OVX females seem to provide a tonic excitatory drive to maintain breathing frequency in normocapnia, and this response may not to be functionally influenced by E2.

Influence of estrous cycle hormonal fluctuations and gonadal hormones on the ventilatory response to hypoxia in female rats.

Sex hormones may influence many physiological processes. Recently, we demonstrated that hormonal fluctuations of cycling female rats do not affect respiratory parameters during hypercapnia. However, it is still unclear whether sex hormones and hormonal fluctuations that occur during the estrous cycle can affect breathing during a hypoxic challenge. Our study aimed to evaluate respiratory, metabolic, and thermal responses to hypoxia in female rats on different days of the estrous cycle (proestrus, estrus, metestrus, and diestrus) and in ovariectomized rats that received replacement with oil (OVX), estradiol (OVX + E2), or a combination of estradiol and progesterone (OVX + E2P). Ventilation (V E), tidal volume (V T), respiratory frequency (fR), oxygen consumption (VO2), and V E/VO2 were not different during the estrous cycle in normoxia or hypoxia. Body temperature (Tb) was higher during estrus, but decreased similarly in all groups during hypoxia. Compared with intact females in estrus, gonadectomized rats also had lower Tb in normoxia, but not in hypoxia. OVX rats experienced a significant drop in the ventilatory response to hypoxia, but hormonal replacement did not restore values to the levels of an intact animal. Our data demonstrate that the different phases of the estrous cycle do not alter ventilation during normoxia and hypoxia, but OVX animals display lower ventilatory responses to hypoxia compared with ovary-intact rats. Because estradiol and progesterone replacement did not cause significant differences in ventilation, our findings suggest that a yet-to-be-defined non-steroidal ovarian hormone is likely to stimulate the ventilatory responses to hypoxia in females.

Static and Functional Balance in Individuals With COPD: Comparison With Healthy Controls and Differences According to Sex and Disease Severity.

BACKGROUND: Studies have shown that individuals with COPD have impaired body balance, probably caused by the disease's multisystemic manifestations plus age-related decline in balance, potentially increasing the risk of falling and its consequences. However, little is known about the profile of individuals with COPD who present balance impairments, especially related to sex and disease severity stages. The aim of this work was to compare static and functional balance between subjects with COPD and healthy controls and to check possible differences according to sex and degrees of disease severity. METHODS: Forty-seven subjects with COPD and 25 healthy controls were included in this study. Their static balance was assessed in one-legged stance using a force platform and functional balance with the Timed Up and Go test. Additionally, participants performed spirometry, the 6-min walk test and isometric quadriceps maximal voluntary contraction assessment. Disease severity was classified according to the Global Initiative for Obstructive Lung Disease stages and BODE (body mass index, air-flow obstruction, dyspnea, and exercise capacity) scores. RESULTS: In comparison with healthy controls, subjects with COPD had worse static (center of pressure displacement area: 9.3 ± 1.9 cm2 vs 11.6 ± 4.0 cm2, respectively, P = .01) and functional balance (Timed Up and Go test: 8.5 ± 1.3 s vs 10.3 ± 1.8 s, respectively, P < .001). In the COPD group, men performed better in the Timed Up and Go test than women (9.8 ± 1.2 s vs 10.9 ± 2.2 s, respectively, P = .03), whereas women presented a better static balance in comparison with men for all parameters related to center of pressure (P < .005 for all). Disease severity did not affect any balance results. CONCLUSIONS: Individuals with COPD had worse static and functional balance in comparison with healthy controls. Sex can mediate these results, depending on the type of balance evaluation (force platform or functional test). Balance performance was similar among the groups classified according to disease severity.

Land Use Influences Niche Size and the Assimilation of Resources by Benthic Macroinvertebrates in Tropical Headwater Streams.

It is well recognized that assemblage structure of stream macroinvertebrates changes with alterations in catchment or local land use. Our objective was to understand how the trophic ecology of benthic macroinvertebrate assemblages responds to land use changes in tropical streams. We used the isotope methodology to assess how energy flow and trophic relations among macroinvertebrates were affected in environments affected by different land uses (natural cover, pasture, sugar cane plantation). Macroinvertebrates were sampled and categorized into functional feeding groups, and available trophic resources were sampled and evaluated for the isotopic composition of 13C and 15N along streams located in the Cerrado (neotropical savanna). Streams altered by pasture or sugar cane had wider and more overlapped trophic niches, which corresponded to more generalist feeding habits. In contrast, trophic groups in streams with native vegetation had narrower trophic niches with smaller overlaps, suggesting greater specialization. Pasture sites had greater ranges of resources exploited, indicating higher trophic diversity than sites with natural cover and sugar cane plantation. We conclude that agricultural land uses appears to alter the food base and shift macroinvertebrate assemblages towards more generalist feeding behaviors and greater overlap of the trophic niches.

The Impact of Implementing a New Computerized Physician Order Entry (CPOE) System on Pharmaceutical Interventions in a Tertiary Brazilian Hospital.

We analyzed trends in pharmaceutical interventions during the implementation of a new computerized physician order entry (CPOE) process in a tertiary hospital in Brazil. The new process utilized an eletronic interface that was designed in-house and an automatic order extension program. The new process reduced the number of order transcriptions and mitigated other potential CPOE-related errors [1].

Hypoxic and hypercapnic ventilatory responses in rats with polycystic ovaries.

In female rats, a single injection of estradiol valerate (EV) results in effects that are similar to those observed in women with polycystic ovary syndrome (PCOS). We hypothesized that EV-induced PCOS affects breathing control based on evidence showing an influence of sex hormones on ventilation. To test this hypothesis, we studied the effects of EV treatment on the ventilation of female rats in air, in 7% CO2 and in 7% O2, at 30, 45 and 60 days after EV injection. The group examined 30 days after EV treatment showed a 61% reduction in the hypercapnic ventilatory response compared to the control group. Basal ventilation, hypoxic ventilatory response, and body temperature were not affected. These results, suggest that the hormonal changes observed in PCOS may result in a temporary inhibition of the central chemoreflex but do not influence basal ventilation or the hypoxic peripheral chemoreflex.

Ventilatory, metabolic, and thermal responses to hypercapnia in female rats: effects of estrous cycle, ovariectomy, and hormonal replacement.

The aim of this study was to examine how estrous cycle, ovariectomy, and hormonal replacement affect the respiratory [ventilation (V̇e), tidal volume, and respiratory frequency], metabolic (V̇o2), and thermoregulatory (body temperature) responses to hypercapnia (7% CO2) in female Wistar rats. The parameters were measured in rats during different phases of the estrous cycle, and also in ovariectomized (OVX) rats supplemented with 17ß-estradiol (OVX+E2), with a combination of E2 and progesterone (OVX+E2P), or with corn oil (OVX+O, vehicle). All experiments were conducted on day 8 after ovariectomy. The intact animals did not present alterations during normocapnia or under hypercapnia in V̇e, tidal volume, respiratory frequency, V̇o2, and V̇e/V̇o2 in the different phases of the estrous cycle. However, body temperature was higher in female rats on estrus. Hormonal replacement did not change the ventilatory, thermoregulatory, or metabolic parameters during hypercapnia, compared with the OVX animals. Nevertheless, OVX+E2, OVX+E2P, and OVX+O presented lower hypercapnic ventilatory responses compared with intact females on the day of estrus. Also, rats in estrus showed higher V̇e and V̇e/V̇o2 during hypercapnia than OVX animals. The data suggest that other gonadal factors, besides E2 and P, are possibly involved in these responses.

Neurochemical and electrical modulation of the locus coeruleus: contribution to CO2drive to breathe.

The locus coeruleus (LC) is a dorsal pontine region, situated bilaterally on the floor of the fourth ventricle. It is considered to be the major source of noradrenergic innervation in the brain. These neurons are highly sensitive to CO2/pH, and chemical lesions of LC neurons largely attenuate the hypercapnic ventilatory response in unanesthetized adult rats. Developmental dysfunctions in these neurons are linked to pathological conditions such as Rett and sudden infant death syndromes, which can impair the control of the cardio-respiratory system. LC is densely innervated by fibers that contain glutamate, serotonin, and adenosine triphosphate, and these neurotransmitters strongly affect LC activity, including central chemoreflexes. Aside from neurochemical modulation, LC neurons are also strongly electrically coupled, specifically through gap junctions, which play a role in the CO2 ventilatory response. This article reviews the available data on the role of chemical and electrical neuromodulation of the LC in the control of ventilation.

Alcohol-related traffic accidents with fatal outcomes in the city of Sao Paulo.

AIMS: The aims of the present study were to characterize fatal traffic accident victims in a major urban center in Brazil and their association with alcohol consumption. METHODS: Cross-sectional study of 907 fatal traffic accident victims in Sao Paulo, in 2005. RESULTS: Adult males between the ages of 25 and 54 represented the majority of cases with positive blood alcohol concentrations (BAC). Overall, males had a higher proportion of BAC and mean BAC than females. Pedestrians, particularly those with no detectable BAC, were typically older than other victims. Most accidents (total and BAC-positive) happened on weekends between midnight and 6 a.m. Considering all victims, 39.4% were positive (BAC over 0.1g/l). When only drivers (automobile, motorcycle and bicycle) were evaluated, 42.3% had BAC over the legal limit (0.6g/l). CONCLUSIONS: Alcohol is associated with nearly half of all traffic accident deaths in the city of Sao Paulo, especially for days and times associated with parties and bars (weekends between 12 a.m. and 6 a.m.).

Role of neurokinin-1 expressing neurons in the locus coeruleus on ventilatory and cardiovascular responses to hypercapnia.

We assessed the role of NK-1 receptors (NK1R) expressing neurons in the locus coeruleus (LC) on cardiorespiratory responses to hypercapnia. To this end, we injected substance P-saporin conjugate (SP-SAP) to kill NK-1 immunoreactive (NK1R-ir) neurons or SAP alone as a control. Immunohistochemistry for NK1R, tyrosine hydroxylase (TH-ir) and Glutamic Acid Decarboxylase (GAD-ir) were performed to verify if NK1R-expressing neurons, catecholaminergic and/or GABAergic neurons were eliminated. A reduced NK1R-ir in the LC (72%) showed the effectiveness of the lesion. SP-SAP lesion also caused a reduction of TH-ir (66%) and GABAergic neurons (70%). LC SP-SAP lesion decreased by 30% the ventilatory response to 7% CO(2) and increased the heart rate (fH) during hypercapnia but did not affect MAP. The present data suggest that different populations of neurons (noradrenergic, GABAergic, and possibly others) in the LC express NK1R modulating differentially the hypercapnic ventilatory response, since catecholaminergic neurons are excitatory and GABAergic ones are inhibitory. Additionally, NK1R-ir neurons in the LC, probably GABAergic ones, seem to modulate fH during CO(2) exposure, once our previous data demonstrated that catecholaminergic lesion does not affect this variable.