Processo de trabalho e sofrimento psíquico de médicos da atenção primária na pandemia do covid-19 / Work process and psychological suffering of primary care physicians during the COVID-19 pandemic

Resumo A organização e o processo de trabalho são espaços privilegiados para reconhecer as forças que levam ao sofrimento psíquico. Este artigo pretende analisar as percepções de médicos(as) da atenção primária à saúde, que atuam no Programa Mais Médicos, sobre as relações entre sofrimento psíquico e processo de trabalho, no contexto da pandemia do coronavirus. Esta pesquisa foi realizada por meio de um estudo de caso, utilizando métodos e técnicas qualitativas para a coleta, descrição e análise dos dados. Foi selecionada uma amostra intencional em conformidade com a técnica de saturação teórica. A coleta de informações foi realizada com ajuda de entrevistas semiestruturadas, seguindo um roteiro construído para atender aos objetivos desta pesquisa. A análise do discurso dos entrevistados articulou categorias de análise extraidas de cinco eixos temáticos que têm pontos de articulação entre si, com consensos e contradições que dão sentido às visões e posições dos atores no campo da saúde. Os resultados evidenciaram a pandemia como catástrofe sanitária e traumática, redimensionando o processo de trabalho e contribuindo para a sobrecarga, conflitos, medo, sentimento de desamparo e sofrimento psíquico. Inúmeras carências, problemas de infraestrutura, burocracia, interferências políticas, descompasso entre a formação e a prática também contribuiram para esse sofrimento.

Abstract Work organization and process are privileged spaces to recognize the forces that lead to psychological suffering. This study aims to analyze the perceptions of physicians of primary health care, who work in the More Doctors Program, on the relation between psychological suffering and work process during the COVID-19 pandemic. This research was conducted with a case study using qualitative data collection, description, and analysis. An intentional sample was selected in accordance with the theoretical saturation technique. Information was collected by semi-structured interviews, following a script built to meet the objectives of this research. The analysis of interviewees' discourse articulated categories of analysis drawn from five thematic axes with points of articulation between them, consensuses and contradictions that give meaning to the visions and positions of the actors in health. Results evinced the pandemic as a health and traumatic catastrophe, resizing the work process and contributing to overload, conflicts, fear, feelings of helplessness, and psychological suffering. Numerous shortcomings, infrastructure problems, bureaucracy, political interference, mismatch between training and practice also contributed to this suffering.

Bamlanivimab reduces nasopharyngeal SARS-CoV-2 RNA levels but not symptom duration in non-hospitalized adults with COVID-19

ImportanceThe antiviral activity and efficacy of anti-SARS-CoV-2 monoclonal antibody (mAb) therapies to accelerate recovery from COVID-19 is important to define. ObjectiveTo determine safety and efficacy of the mAb bamlanivimab to reduce nasopharyngeal (NP) SARS-CoV-2 RNA levels and symptom duration. DesignACTIV-2/A5401 is a randomized, blinded, placebo-controlled platform trial. Two dose cohorts were enrolled between August 19 and November 17, 2020 for phase 2 evaluation: in the first, participants were randomized 1:1 to bamlanivimab 7000 mg versus placebo, and in the second to bamlanivimab 700 mg versus placebo. Randomization was stratified by time from symptom onset ([≤] or >5 days) and risk of progression to severe COVID-19 ("higher" vs "lower"). SettingMulticenter trial conducted at U.S. sites. ParticipantsNon-hospitalized adults [≥]18 years of age with positive SARS-CoV-2 antigen or nucleic acid test within 7 days, [≤]10 days of COVID-19 symptoms, and with oxygen saturation [≥]92% within 48 hours prior to study entry. InterventionSingle infusion of bamlanivimab (7000 or 700 mg) or placebo. Main Outcomes and MeasuresDetection of NP SARS-CoV-2 RNA at days 3, 7, 14, 21, and 28, time to improvement of all of 13 targeted COVID-19 symptoms by daily self-assessment through day 28, and grade 3 or higher treatment emergent adverse events (TEAEs) through day 28. Secondary measures included quantitative NP SARS-CoV-2 RNA, all-cause hospitalizations and deaths (composite), area under the curve of symptom scores from day 0 through day 28, plasma bamlanivimab concentrations, plasma and serum inflammatory biomarkers, and safety through week 24. ResultsNinety-four participants were enrolled to the 7000 mg cohort and 223 to the 700 mg cohort and initiated study intervention. The proportion meeting protocol criteria for "higher" risk for COVID-19 progression was 42% and 51% for the 7000 and 700 mg cohort, respectively. Median time from symptom onset at study entry for both cohorts was 6 days. There was no difference in the proportion with undetectable NP SARS-CoV-2 RNA at any post-treatment timepoints (risk ratio compared to placebo, 0.82-1.05 for 7000 mg dose [overall p=0.88] and 0.81-1.21 for 700 mg dose [overall p=0.49]), time to symptom improvement (median of 21 vs 18.5 days, p=0.97, for 7000 mg bamlanivimab vs placebo and 24 vs 20.5 days, p=0.08, for 700 mg bamlanivimab vs placebo), or grade 3+ TEAEs with either dose compared to placebo. Median NP SARS-CoV-2 RNA levels were lower at day 3 and C-reactive protein, ferritin, and fibrinogen levels significantly reduced at days 7 and 14 for bamlanivimab 700 mg compared to placebo, with similar trends observed for bamlanivimab 7000 mg. Viral decay modeling supported more rapid decay with bamlanivimab compared to placebo. Conclusions and RelevanceTreatment with bamlanivimab 7000 mg and 700 mg was safe and compared to placebo led to more rapid reductions in NP SARS-CoV-2 RNA and inflammatory biomarkers, but did not decrease time to symptom improvement. The clinical utility of mAbs for outcomes other than hospitalizations and deaths is uncertain. Trial RegistrationClinicalTrials.gov Identifier: NCT04518410 KEY POINTSO_ST_ABSQuestionC_ST_ABSWhat is the safety and efficacy of bamlanivimab monoclonal antibody (mAb) treatment for mild to moderate COVID-19? FindingsIn this randomized, placebo-controlled phase 2 trial of 317 non-hospitalized adults with COVID-19, there was no relationship between symptoms or disease progression risk and nasopharyngeal (NP) virus shedding. Bamlanivimab was safe and reduced NP SARS-CoV-2 RNA levels and inflammatory biomarker levels more than placebo, but did not shorten symptom duration. MeaningNasal virus shedding was not associated with symptoms or baseline risk factors for severe COVID-19. Bamlanivimab, which has been associated with reduced hospitalizations in high-risk individuals, demonstrated antiviral activity with early post-treatment NP sampling but did not accelerate symptom improvement. The clinical utility of bamlanivimab for outcomes other than hospitalizations and deaths, including longer-term outcomes, is uncertain.

In vivo kinetics of SARS-CoV-2 infection and its relationship with a person's infectiousness

The within-host viral kinetics of SARS-CoV-2 infection and how they relate to a persons infectiousness are not well understood. This limits our ability to quantify the impact of interventions on viral transmission. Here, we develop data-driven viral dynamic models of SARS-CoV-2 infection and estimate key within-host parameters such as the infected cell half-life and the within-host reproductive number. We then develop a model linking VL to infectiousness, showing that a persons infectiousness increases sub-linearly with VL. We show that the logarithm of the VL in the upper respiratory tract (URT) is a better surrogate of infectiousness than the VL itself. Using data on VL and the predicted infectiousness, we further incorporated data on antigen and reverse transcription polymerase chain reaction (RT-PCR) tests and compared their usefulness in detecting infection and preventing transmission. We found that RT-PCR tests perform better than antigen tests assuming equal testing frequency; however, more frequent antigen testing may perform equally well with RT-PCR tests at a lower cost, but with many more false-negative tests. Overall, our models provide a quantitative framework for inferring the impact of therapeutics and vaccines that lower VL on the infectiousness of individuals and for evaluating rapid testing strategies. SignificanceQuantifying the kinetics of SARS-CoV-2 infection and individual infectiousness is key to quantitatively understanding SARS-CoV-2 transmission and evaluating intervention strategies. Here we developed data-driven within-host models of SARS-CoV-2 infection and by fitting them to clinical data we estimated key within-host viral dynamic parameters. We also developed a mechanistic model for viral transmission and show that the logarithm of the viral load in the upper respiratory tract serves an appropriate surrogate for a persons infectiousness. Using data on how viral load changes during infection, we further evaluated the effectiveness of PCR and antigen-based testing strategies for averting transmission and identifying infected individuals.

Renovascular hypertension: Effects of mesenchymal stem cells in the contralateral hypertensive kidney in rats.

Mesenchymal stem cells (MSC) induced neovascularization and improved renal morphology of the stenotic kidney in 2 kidneys-1 clip (2K-1C) model of renovascular hypertension. The present study evaluated the effects of MSC in the contralateral hypertensive kidney. Three weeks after left renal artery occlusion, MSC were injected into the tail vein of the 2K-1C rats. Renal function and morphology were analyzed in both kidneys. Labeled MSC were found in stenotic and contralateral kidneys. Hypertensive 2K-1C animals presented increased circulating levels of Angiotensin II (Ang II) and renin. MSC prevented the progressive increase of blood pressure and reduced circulating Ang II and renin levels. Stenotic kidney showed reduced renal plasma flow (RPF) and glomerular filtration rate (GFR), whereas the contralateral kidney had a tendency (p > 0.5) of reduction in GFR in spite of unchanged RPF. MSC treatment caused an improvement in GFR with no effect of on RPF in the stenotic kidney. Contralateral kidney showed increased diuresis and natriuresis that were even higher in MSC-treated animals, indicating that cell treatment improved the capacity of the contralateral kidney to excrete sodium. Contralateral kidney expressed higher levels of inflammatory cytokines (IL-6, TNF-α) and signs of fibrosis, which were attenuated by MSC treatment. MSC treatment improved the stenotic kidney function, and it was also beneficial to the contralateral hypertensive kidney because it improved the morphology and preserved its capacity to excrete sodium.

Chronic Nicotine Exposure Abolishes Maternal Systemic and Renal Adaptations to Pregnancy in Rats.

Pregnancy is characterized by maternal systemic and intrarenal vasodilation, leading to increases in the renal plasma flow (RPF) and glomerular filtration rate (GFR). These responses are mainly mediated by nitric oxide (NO) and relaxin. The impact of cigarette smoking on the maternal adaptations to pregnancy is unclear. Here we evaluated the effects of chronic exposure to nicotine on systemic and intrarenal parameters in virgin (V) and 14-day pregnant (P) Wistar rats. V and P groups received saline or nicotine (6 mg·kg(-1)·day(-1)) respectively, via osmotic minipumps for 28 days, starting 14 days before pregnancy induction. Nicotine induced a 10% increase in blood pressure in the V group and minimized the characteristic pregnancy-induced hypotension. Renal sympathetic nerve activity (rSNA) and baroreflex sensitivity were impaired by nicotine mainly in the P group, indicating that the effect of nicotine on blood pressure was not mediated by nervous system stimulation. Nicotine had no effect on GFR in the V rats but reduced GFR of the P group by 30%. Renal expression of sodium and water transporters was downregulated by nicotine, resulting in increased fractional sodium excretion mainly in the P group, suggesting that nicotine compromised the sodium and water retention required for normal gestation. There was a reduction in the expression of inducible NO synthase (iNOS) in both the kidney tissue and renal artery, as well as in the expression of the relaxin receptor (LGR7). These results clearly show that nicotine induced deleterious effects in both virgin and pregnant animals, and abolished the maternal capacity to adapt to pregnancy.

Impact of angiogenic therapy in the treatment of critical lower limb ischemia in an animal model.

Angiogenic therapies for critical limb ischemia were tested in a mouse model. The mice were anesthetized and their femoral arteries were ligated. The animals were treated with bone marrow mononuclear cells (BMMCs) alone, BMMCs combined with plasmid vector encoding granulocyte macrophage colony-stimulating factor (GM-CSF), received no treatment, or no intervention (controls). The degree of ischemia was monitored for 4 weeks using a visual scale. Muscle atrophy and strength were assessed at 4 weeks postoperatively; the mice were then killed. In treated animals, total necrosis of the limb was not found, the weight of the gastrocnemius and quadriceps muscles was significantly higher, functional ability and tissue regeneration were significantly increased, and muscle impairment and adipocyte presence were significantly reduced compared with untreated animals. At inducing angiogenesis, the BMMCs alone was more effective than BMMCs combined with plasmid vector encoding GM-CSF. Treated animals showed increased angiogenesis compared with ischemic untreated ones.

Increased renal sympathetic nerve activity leads to hypertension and renal dysfunction in offspring from diabetic mothers.

The exposure of the fetus to a hyperglycemic environment promotes the development of hypertension and renal dysfunction in the offspring at adult age. We evaluated the role of renal nerves in the hypertension and renal changes seen in offspring of diabetic rats. Diabetes was induced in female Wistar rats (streptozotocin, 60 mg/kg ip) before mating. Male offspring from control and diabetic dams were studied at an age of 3 mo. Systolic blood pressure measured by tail cuff was increased in offspring of diabetic dams (146 ± 1.6 mmHg, n = 19, compared with 117 ± 1.4 mmHg, n = 18, in controls). Renal function, baseline renal sympathetic nerve activity (rSNA), and arterial baroreceptor control of rSNA were analyzed in anesthetized animals. Glomerular filtration rate, fractional sodium excretion, and urine flow were significantly reduced in offspring of diabetic dams. Two weeks after renal denervation, blood pressure and renal function in offspring from diabetic dams were similar to control, suggesting that renal nerves contribute to sodium retention in offspring from diabetic dams. Moreover, basal rSNA was increased in offspring from diabetic dams, and baroreceptor control of rSNA was impaired, with blunted responses to infusion of nitroprusside and phenylephrine. Thus, data from this study indicate that in offspring from diabetic mothers, renal nerves have a clear role in the etiology of hypertension; however, other factors may also contribute to this condition.

Blood pressure reducing effects of Phalaris canariensis in normotensive and spontaneously hypertensive rats.

The birdseed Phalaris canariensis (Pc) is popularly used as an antihypertensive agent. The aqueous extract of Pc (AEPc) was administered in adult normotensive Wistar rats and spontaneously hypertensive rats (SHR) and in prehypertensive young SHR (SHR(Y), 3 weeks old). Animals received AEPc (400 mg·kg(-1)·day(-1), by gavage) for 30 days, then groups were divided into 2 subgroups: one was treated for another 30 days and the other received water instead of AEPc for 30 days. AEPc reduced systolic blood pressure (SBP) in both adult groups; however, treatment interruption was followed by a gradual return of the SBP to baseline levels. SHR(Y) became hypertensive 30 days after weaning. AEPc minimized the increase in SBP in SHR(Y), but blood pressure rose to levels similar to those in the untreated group with treatment interruption. There were no changes in renal function, diuresis, or Na(+) excretion. Pc is rich in tryptophan, and the inhibition of the metabolism of tryptophan to kynurenine, a potential vasodilator factor, prevented the blood pressure reducing effect of AEPc. Moreover, AEPc significantly reduced sympathoexcitation. Data indicate that the metabolic derivative of tryptophan, kynurenine, may be a mediator of the volume-independent antihypertensive effect of Pc, which was at least in part mediated by suppression of the sympathetic tonus.

High sucrose intake in rats is associated with increased ACE2 and angiotensin-(1-7) levels in the adipose tissue.

Sucrose-fed rats, a model of metabolic syndrome, are characterized by insulin resistance, obesity, hypertension, and high plasma levels of triacylglycerols and angiotensin II (Ang II). However, whether tissue renin-angiotensin system (RAS) is altered in metabolic syndrome is unclear. To study this issue, food ad libitum and water (C) or 20% sucrose solution (SC) were given to adult male Wistar rats, for 30 days. Body weight (BW), blood pressure (BP), epididymal adipose tissue (EPI) mass, rate of in vivo fatty acid (FA) synthesis in EPI, circulating glucose, insulin, leptin, angiotensins I and II, triacylglycerols, and plasma renin (PRA) and angiotensin-converting enzyme (ACE) activities were evaluated. In kidneys and EPI, gene and protein expression of type 1 (AT(1)) and 2 (AT(2)) Ang II receptors, ACE, angiotensinogen (AGT) as well as protein expression of angiotensin-converting enzyme 2 (ACE2) were determined. In both tissues, Ang I, Ang II and Ang-(1-7) contents were also measured by HPLC. In SC rats higher BP, EPI mass, circulating triacylglycerols, insulin, leptin, PRA and, Ang II were found. In EPI, the rate of in vivo FA synthesis was associated with increased Ang-(1-7), protein expression of AT(1) and AT(2) receptors, ACE2, AGT, and gene expression of AGT although a reduction in ACE activity and in adipose Ang I and Ang II contents was observed. In kidneys, AT(1) and AT(2), ACE and AGT gene and protein expression as well as protein expression of ACE2 were unaltered while Ang II, Ang-(1-7) and ACE activity increased. These RAS component changes seem to be tissue specific and possibly are related to enhancement of FA synthesis, EPI mass and hypertension.

Synergistic effect of vascular endothelial growth factor and granulocyte colony-stimulating factor double gene therapy in mouse limb ischemia.

BACKGROUND: Vascular endothelial growth factor (VEGF) has mostly been tested to treat ischemic diseases, although the outcomes obtained are not satisfactory. Our hypothesis is that the local transient expression of VEGF and stem cell mobilizer granulocyte colony-stimulating factor (G-CSF) genes in ischemic limbs can complement their activities and be more efficient for limb recovery. METHODS: Limb ischemia was surgically induced in mice and 50 microg of VEGF and/or G-CSF genes were locally transferred by electroporation. After 3-4 weeks, evidence of necrosis by visual inspection, capillary density, muscle mass, muscle force and hematopoietic cell mobilization were evaluated. RESULTS: After 4 weeks, 70% and 90% of the animals of the ischemic group (IG) and VEGF-treated group (VG), respectively, presented limb necrosis, in contrast to only 10% observed in the group of mice treated with both VEGF and G-CSF genes (VGG). Recovery of muscle mass and muscle force was higher than 60% in the VGG compared to the non-ischemic group. The mobilization of Sca1+ cells and neutrophils was also higher in the VGG, which may explain the lower level of necrosis observed in this group (22%, in contrast to 70% in the IG). Capillary density and degree of fibrosis were determined in weeks 3 and 4, and also showed a clear benefit as a result of the use of the G-CSF and VEGF genes together. CONCLUSIONS: Gene therapy using VEGF and G-CSF demonstrated a synergistic effect promoting vessel and tissue repair in mouse hind limb ischemia.

Vitamin C prevents DNA damage induced by renovascular hypertension in multiple organs of Wistar rats.

The aim of this study was to investigate, through the single-cell gel (comet) assay, whether vitamin C is able to protect against renovascular hypertension-induced genotoxicity in multiple organs. A total of 32 male Wistar rats were divided into four groups: negative control (n = 6); animals treated with vitamin C (n = 6); hypertensive rats (n = 10) and hypertensive rats and treated with vitamin C (n = 10). Hypertension was induced as a result of partial obstruction of the left renal artery by means of a silver clip during 6 weeks. Vitamin C was administered at 150 mg/kg during 7 consecutive days before the end of the experimental period. The results showed that vitamin C was able to protect blood cells against hypertension-induced genotoxicity. Brain, liver and heart cells were also protected by vitamin C following hypertension-induced genotoxic damage. Regarding blood pressure, vitamin C reduced the hypertensive state. In conclusion, our results suggest that vitamin C can prevent hypertension-induced DNA damage in blood, liver, brain and heart cells as well as to normalize the blood pressure of rats.

Altered balance of gamma-aminobutyric acidergic and glutamatergic afferent inputs in rostral ventrolateral medulla-projecting neurons in the paraventricular nucleus of the hypothalamus of renovascular hypertensive rats.

An imbalance of excitatory and inhibitory functions has been shown to contribute to numerous pathological disorders. Accumulating evidence supports the idea that a change in hypothalamic gamma-aminobutyric acid (GABA)-ergic inhibitory and glutamatergic excitatory synaptic functions contributes to exacerbated neurohumoral drive in prevalent cardiovascular disorders, including hypertension. However, the precise underlying mechanisms and neuronal substrates are still not fully elucidated. In the present study, we combined quantitative immunohistochemistry with neuronal tract tracing to determine whether plastic remodeling of afferent GABAergic and glutamatergic inputs into identified RVLM-projecting neurons of the hypothalamic paraventricular nucleus (PVN-RVLM) contributes to an imbalanced excitatory/inhibitory function in renovascular hypertensive rats (RVH). Our results indicate that both GABAergic and glutamatergic innervation densities increased in oxytocin-positive, PVN-RVLM (OT-PVN-RVLM) neurons in RVH rats. Despite this concomitant increase, time-dependent and compartment-specific differences in the reorganization of these inputs resulted in an altered balance of excitatory/inhibitory inputs in somatic and dendritic compartments. A net predominance of excitatory over inhibitory inputs was found in OT-PVN-RVLM proximal dendrites. Our results indicate that, along with previously described changes in neurotransmitter release probability and postsynaptic receptor function, remodeling of GABAergic and glutamatergic afferent inputs contributes as an underlying mechanism to the altered excitatory/inhibitory balance in the PVN of hypertensive rats.

Granulocyte-macrophage colony-stimulating factor gene based therapy for acute limb ischemia in a mouse model.

BACKGROUND: Granulocyte-colony-stimulating factor (GM-CSF) is a pleiotropic factor for hematopoiesis that stimulates myeloblasts, monoblasts and mobilization of bone marrow stem cells. Therefore, the GM-CSF gene is a potential candidate for vessel formation and tissue remodeling in the treatment of ischemic diseases. METHODS: A new mouse limb ischemia was established by surgery and gene transfer was performed by injection of 100 microg of a plasmid carrying GM-CSF. Muscle force and weight, histology, capillary density, circulating stem cells and monocytes were determined after 3-4 weeks. RESULTS: More than 60% of nontreated ischemic animals showed gangrene below the heel after 4 weeks, whereas the GM-CSF gene-treated animals showed only darkening of nails or toes. These animals demonstrated a full recovery of the affected muscles in terms of weight, force and muscle fiber structure, but the muscles of nontreated ischemic animals lost approximately 50% weight, 86% force and their regular structure. When the GM-CSF gene was injected into the contralateral limb, only partial loss was observed, demonstrating a distant effect of GM-CSF. The capillary density in the GM-CSF-treated group was 52% higher in relation to the nontreated group. Blood analysis by flow cytometry showed that the GM-CSF-treated group had 10-20% higher levels of circulating monocytes and Sca-1(+). CONCLUSIONS: We conclude that the direct administration of GM-CSF gene in limb ischemia had a strong therapeutic effect because it promoted the recovery of muscle mass, force and structure by mobilizing therapeutic cells and augmenting the number of vessels.

Differential baroreceptor modulation mediated by the ventrolateral medulla.

Previous studies have shown that pharmacological stimulation of a region denominated caudal pressor area (CPA), located in the caudal end of the ventrolateral medulla, induces increases in arterial blood pressure (BP). The aim of this study was to compare the responses on renal sympathetic nerve activity (rSNA) and BP responses mediated by stimulation of CPA or rostral ventrolateral medulla (RVLM), in intact or sino-aortic barodenervated rats. Male Wistar rats (300-350 g, n=15) were anesthetized (urethane 1.2 to 1.4 g/kg, i.v.) and artificially ventilated. The mean arterial pressure (MAP) and rSNA were measured during bilateral glutamate microinjection (10 nmo/100 nl) into the CPA or into the RVLM. Glutamatergic stimulation of the RVLM increased MAP (46+/-7 mm Hg) and rSNA (82+/-21%); during CPA stimulation, MAP and rSNA increased 60+/-7 mm Hg and 93+/-9%, respectively. However, despite the similarity of responses mediated by both regions, the duration of rSNA and blood pressure responses mediated by the CPA were significantly longer than the duration of the responses mediated by the RVLM. After barodenervation, there was an increase in the time-course and magnitude of sympathetic response only in response to RVLM stimulation but not in response to CPA. The results suggest a differential baroreceptor modulation on rSNA mediated by the ventrolateral medulla neurons. Glutamatergic activation of CPA neurons can cause large increases in the rSNA and BP with a weaker baroreceptor modulation when compared to responses mediated by the RVLM neurons.

Effects of chronic anabolic steroid treatment on tonic and reflex cardiovascular control in male rats.

The aim of this study was to analyze the cardiovascular effects of chronic stanozolol administration in male rats. The rats were randomly assigned to one of three groups: (1) control (n=12), (2) chronic treatment with low dose of stanozolol (LD, n=18, 5 mg/kgweek) and; (3) treatment with high dose of stanozolol (HD, n=28, 20 mg/kgweek). Mean arterial pressure (MAP) was higher in both HD (128+/-2.2 mmHg) and LD (126+/-2.5 mmHg) than control (116+/-2 mmHg). The LD group showed an increase in cardiac output (control 121+/-2.5, LD 154+/-5.9 ml/min), whereas in the HD group total peripheral resistance increased (control 1.03+/-0.07, HD 1.26+/-0.07 mmHg/ml/min). Acute sympathetic blockade caused a similar decrease in MAP in all groups. In conscious rats, the baroreflex index for bradycardia (control -3.7+/-0.4, LD -2.0+/-0.1 beat/mmHg) and tachycardia (control -3.6+/-0.3, LD -4.7+/-0.2 beat/mmHg) responses changed only in the LD group. Cardiac hypertrophy was observed in both treated groups (P<0.05). In conclusion, hypertension with differential hemodynamic changes and alterations in the reflex control in heart rate is seen at different stanozolol doses, which may be important variables in the cardiovascular effects of anabolic steroids.

Haemodynamic effects of hypothalamic disconnection in anaesthetized rats.

The aim of the present study was to analyse the haemodynamic effects induced by the hypothalamic disconnection (HD) caudal or rostral to the paraventricular nucleus of the hypothalamus (PVN). Mean arterial pressure (MAP), hindlimb, renal and mesenteric blood flow and vascular conductance (HVC, RVC and MVC, respectively) were measured in urethane (1.2 g/kg, i.v.) anesthetized rats for 60 min after disconnection. HD caudal to the PVN was performed with a double-edged microknife of bayonet shape (R = 1 mm, H= 2 mm) stereotaxically placed, lowered 2.8 mm caudal to the bregma along the midline. The cut was achieved by rotating the microknife 90 degrees right and 90 degrees left. HD rostral to the PVN was performed with the knife placed 0.8 mm caudal to the bregma. Thirty minutes after the hypothalamic disconnection caudal (HD-C), a decrease in MAP was observed (- 14 +/- 3 mm Hg), reaching a 60-min decrease of 30 +/- 3 mm Hg. Hindlimb conductance increased 10 min after HD (156 +/- 14%) and remained elevated throughout the experimental period. On the contrary, we observed a transitory renal vasoconstriction (82 +/- 9%, < or = 20 min) and a late mesenteric vasodilation, starting at 30 min (108 +/- 4%) and reaching 138 +/- 6% at 60 min. In rats with HD rostral to the PVN, we only observed minor changes in the cardiovascular parameters. In the MAP, there was a slight decrease 60 min after the hypothalamic disconnection rostral (HD-R) (-9 +/- 4 mm Hg). There were no significant changes in HVC. RVC and MVC were increased 60 min after the HD-R (116 +/- 12% and 124 +/- 11%, respectively). These results suggest that vasodilation in the hindlimb and in the mesenteric bed could contribute to the observed decrease in MAP in HD caudal to PVN rats.

Papel da suoerfície ventrolateral do bulbo no controle cardiovascular / Role of ventrolateral surface of the medulla oblongatta on cardiovascular control

No presente trabalho, três capítulos foram apresentados com enfoque na participaçao da regiao ventral bulhar no controle cardiovascular. Os principais achados foram: 1)A regiao RVL contém neurônios que controlam o débito cardíaco e resistência periférica total. Respostas diferenciadas sobre tais variáveis puderam ser obtidas, como relatado no capítulo I. 2)A atividade simpática cardíaca pode ser preferencialmente ou exclusivamente controlada por populaçoes de neurônios RVL localizados mais rostralmente no núcleo, quando comparado com neurônios vasoconstritores musculares, localizados mais caudal-mente, como relatado no capítulo I. 3)A regiao RVL controla funçoes cardíacas específicas como: inotropismo, cronotropismo ou dromotropismo. Aparentemente, respostas cronotrópicas sao mais evidentes quando a regiao RVL direita foi estimulada e respostas dromotrópicas foram mais evidentes quando a regiao RVL esquerda foi ativada, como relatado no capítulo I. 4)Além da regiao RVL, a inibiçao da APC produz queda da PA. As açoes da APC dependem da atividade da regiao porém, o inverso nao ocorre. As alteraçoes de PA em resposta à estimulaçao ou inibiçao da APC em parte sao integradas na regiao CVL, como relatado no capítulo II. 5)A atividade de neurônios RVL é dependente da integridade da APC. A inibiçao dessa regiao produz substancial queda na atividade espontânea de neurônios barossensitivos e reticuloespinais Rostroventrolaterais, como relatado no capítulo II...(au)