O trauma pélvico apresenta alta morbi-mortalidade, especialmente nos casos de dupla ruptura do anel pélvico (AP), devido à hemorragia. O objetivo deste trabalho é observar o tempo transcorrido até a realização do tratamento endovascular (TE), a sua eficácia e a estratégia de exames complementares empregado. 53 pacientes com fratura de bacia póstraumática foram submetidos a embolização arterial num estudo retro e prospectivo, realizado no período de janeiro de 2000 e dezembro de 2005. A idade dos pacientes variou entre 93 e 17 anos, com média de 37,5 anos. Houve predomínio do sexo masculino, com cerca de 62,2%. A causa do trauma mais freqüente foi o acidente de moto em 36% dos casos. Predominaram as fraturas com dupla ruptura do AP em 71,6 % dos casos. 49 pacientes apresentavam instabilidade hemodinâmica, e desses, todos receberam derivados sanguíneos previamente à realização do TE. Neste estudo 38,7% (n = 19) dos pacientes instáveis foram submetidos ao exame de tomografia computadorizada (TC) antes do TE, o tempo médio desse grupo para atingir a sala de radiologia vascular foi de 230,45 minutos. Nos pacientes enviados diretamente à arteriografia com intenção terapêutica, o tempo médio até início da realização do tratamento foi de 146,77 minutos. A diferença entre as taxas de mortalidade precoce nos grupos de pacientes submetidos ou não a TC previamente ao TE foi de 5,63%. O choque hemorrágico foi à causa de óbito em 63,33% dos pacientes que apresentaram mortalidade precoce. Na conduta inicial desses pacientes preconiza-se realizar o menor número de intervenções até o controle da hemorragia. O tempo transcorrido até a chegada na sala de radiologia vascular é fator importante no prognóstico dos pacientes com fraturas hemorrágicas da bacia. O TE precoce é uma importante ferramenta nos pacientes hemodinamicamente instáveis inicialmente / Pelvic trauma presents high morbi-mortality specially in cases of double rupture of pelvic ring due to hemorrhages. The objective of this work is to observe the time period since the rupture till the execution of endovascular treatment (ET) as well as the effectiveness and strategy for the used complementary exam. 53 patients with pos-traumatic pelvic fracture were submitted to arterial embolization during retro and prospective study. Such study was executed during the period of January 2000 to December 2005. The age of the patients varied between 17 and 93 years old, average 37.5 year old and predominantly men at about 62.2% of the cases. The most frequent cause of the traumas, 36%, was motorcycle accident. Predominantly fractures with double rupture of the pelvic ring, that is 71.6% of the cases. 49 patients presented hemodynamic instability, all of them received blood derivatives previously to the ET execution. In this study 38.7% (n=19) of the unstable patients were submitted to computerized tomography exam (CT) before the ET. The average period of time for this group to reach the room of vascular radiology was 230.45 min. For patients sent straight to arteriography with therapeutic intention, the average period time was 146.77 min. The difference, between the early mortality rate of the group undertaken or not to the CT previously to the ET, was 5.63%. The hemorrhagic shock was the cause of death in 63.33% patients, who presented early mortality. For the initial on going study of these patients, we recommend to accomplish the least number of interventions until hemorrhage is controlled. The elapsed time till the arrival at the vascular radiology room is an important factor to make prognosis about patients with hemorrhagic pelvic fractures. The early ET is an important tool for patients with hemodynamic instability

<p>Abstract</p><p>Crimean-Congo Hemorrhagic Fever virus (CCHF) and Lassa virus are giving sources illness to humans. In addition to zoonotic transmission, CCHF and Lassa virus can spread from person to person. After a short incubation period, CCHF and Lassa virus infections are characterized by a sudden onset of high fever, chills, headache and cough just like flu. Even some people are vomiting and have diarrhoea. After a few days of illness hemorrhagic manifestations occur. Treatment options for CCHF and Lassa viruses are limited, and there is no vaccine available for use in humans. The purpose of the present study was to produce recombinant nucleocapsid protein of Lassavirus and CCHF virus including an aminoterminal His-tag by a Semliki Forest Virus Replicon (pSFV 4.2). The recombinant proteins are planned to be used in future development of diagnostic methods.</p>

Abstract Crimean-Congo Hemorrhagic Fever virus (CCHF) and Lassa virus are giving sources illness to humans. In addition to zoonotic transmission, CCHF and Lassa virus can spread from person to person. After a short incubation period, CCHF and Lassa virus infections are characterized by a sudden onset of high fever, chills, headache and cough just like flu. Even some people are vomiting and have diarrhoea. After a few days of illness hemorrhagic manifestations occur. Treatment options for CCHF and Lassa viruses are limited, and there is no vaccine available for use in humans. The purpose of the present study was to produce recombinant nucleocapsid protein of Lassavirus and CCHF virus including an aminoterminal His-tag by a Semliki Forest Virus Replicon (pSFV 4.2). The recombinant proteins are planned to be used in future development of diagnostic methods.

African monkey species are natural hosts of simian hemorrhagic fever virus (SHFV) and develop persistent, asymptomatic infections. SHFV was previously shown to also cause a rapid onset fatal hemorrhagic fever disease in macaques. Infection of macaques with a new isolate of SHFV from persistently infected baboon sera, that showed high nucleotide identity with the lab strain LVR, resulted in viremia, pro-inflammatory cytokine and tissue factor production, and symptoms of coagulation defects. Primary macrophages and myeloid dendritic cell cultures from disease-susceptible macaques efficiently replicated SHFV and produced pro-inflammatory cytokines, including IL-6 and TNF-α, as well as tissue factor. Cells from disease resistant baboons produced low virus yields and the immunomodulatory cytokine IL-10. IL-10 treatment of macaque cells decreased IL-6 levels but had no effect on TNF-α levels, tissue factor or virus production suggesting that IL-10 plays a role in modulating immunopathology in disease-resistant baboons but not in regulating the efficiency of virus replication. SHFV is a member of the family Arteriviridae. The SHFV genome encodes 8 minor structural proteins. Other arteriviruses encode 4 minor structural proteins. Amino acid sequence comparisons suggest that the four additional SHFV minor structural proteins resulted from gene duplication. A full-length infectious clone of SHFV was constructed and produced virus with replication kinetics comparable to the parental virus. Mutant infectious clones, each with the start codon of one of the minor structural proteins substituted, were analyzed. All eight SHFV proteins were required for infectious virus production. The SHFV nonstructural polyprotein is processed into the mature replicase proteins by several viral proteases including papain-like cysteine proteases (PLPs). Only one or two PLP domains are present in other arteriviruses but SHFV has three PLP domains. Analysis of in vitro proteolytic processing of C- and N-terminally tagged polyproteins indicated that the PLP in each of the three SHFV nsp1 proteins is active. However, the nsp1α protease is more similar to a cysteine protease than a PLP. Analysis of the subcellular localization of the three SHFV nsp1 proteins indicated they have divergent functions.

The flavivirus West Nile virus (WNV) encodes a single polyprotein that is processed into three structural and seven nonstructural proteins. Various WNV bicistronic replicons that direct cap-dependent translation of an N-terminal viral capsid or capsid/Renilla luciferase fusion protein as well as IRES-dependent translation of the nonstructural proteins were constructed. An original replicon consisting of the WNV 5' NCR, the 5' 198 nts of the capsid coding sequence, which included the 5' cyclization sequence (Cyc), and an EMCV IRES followed by the WNV nonstructural genes and 3' NCR was generated. Real time qRT-PCR analysis of intracellular levels of this replicon RNA showed a 4 fold increase by 96 hr after transfection of BHK cells. Increasing the distance between the 5' Cyc and IRES by insertion of a 5' IRES flanking sequence alone or together with a Renilla luciferase reporter did not increase RNA replication. Addition of only a reporter decreased RNA replication. The insertion of an extended capsid coding sequence also did not enhance RNA replication, but did enhance both cap- and IRES-dependent translation of replicon RNA, as indicated by immunofluorescence and Western blot analysis. These results suggest the presence of a translation enhancer in the 3' portion of the capsid coding region. Simian hemorrhagic fever virus (SHFV) is a member of the family Arteriviridae, order Nidovirales. SHFV is unique among Nidoviruses in having three instead of two papain-like cysteine protease (PCP) motifs designated alpha, beta, and gamma, within the N-terminal region of its ORF1a. Mutations of putative PCP cleavage sites showed that the most efficient cleavage was by PCP beta at its downstream cleavage site. A large deletion located between the two catalytic residues of PCP alpha was hypothesized to render this protease inactive. However, processing was observed at the cleavage site following PCP alpha. Mutational analyses confirmed that PCP alpha is an inactive protease, and that the cleavage sites downstream of PCP alpha are cleaved by PCP gamma. When the catalytic residues of PCP gamma were mutated, PCP beta was also able to back cleave at these sites. This "back" cleavage is a previously unreported activity for an arterivirus PCP.

Puumala hantavirus (PUUV) causes hemorrhagic fever with renal syndrome in Europe. After inhalation of virus shed by bank voles, the virus systemically targets the vascular endothelium leading to vascular dysfunction and leakage. Many patients with PUUV infection experience cardiopulmonary manifestations but the underlying mechanisms have not been determined. The aims of the studies presented were to describe cardiopulmonary manifestations, investigate pathogenetic mechanisms including presence of virus in the lungs and the local immune response in PUUV infection. The results showed cardiopulmonary involvement of varying severity in almost all studied patients. High-resolution computed tomography frequently revealed vascular leakage into the lungs or pleural cavities. Pulmonary function tests generally showed reduced gas diffusing capacity, evidenced in patients as dyspnea, poor oxygenation and frequent need of oxygen treatment. Among patients who were not fully recovered at 3 months follow-up, remaining decreased gas diffusing capacity was highly common. Echocardiography revealed mainly right heart dysfunction which was related to manifestations within the lungs, in terms of increased estimated pulmonary vascular resistance, mild to moderate pulmonary hypertension, and reduced right ventricular systolic function in patients with more pronounced lung involvement, as indicated by need of oxygen treatment. Analyses on bronchoalveolar lavage (BAL) and bronchial biopsies revealed a highly activated cytotoxic T cell (CTL) response in the lungs. The CTL response was not balanced by the expansion of regulatory T cells and high numbers of CTLs were associated with more severe disease. PUUV RNA was detected in almost all patients’ BAL samples and the viral load was inversely correlated to the number of CTLs. Three patients presenting with severe and fatal cardiopulmonary distress were also described. Autopsies revealed PUUV protein in vascular endothelium in all investigated organs, including the heart and lungs, along with a massive CTL response mainly in the lungs. In conclusion, cardiopulmonary involvement of varying severity was present in almost all patients with PUUV infection. Cytotoxic immune responses could contribute to disease development but also help in clearing the infection. Long lasting fatigue after hantavirus infection may be explained by remaining manifestations within the lungs.

Diss. (sammanfattning) Stockholm : Karol. inst., 2005. / Härtill 5 uppsatser.

Το αιμορραγικό shock (H/S) έχει δειχθεί πως προκαλεί οξειδωτικό stress (OS) σε διάφορους ιστούς λόγω της υπερπαραγωγής ελευθέρων ριζών οξυγόνου στη φάση της επαναιμάτωσης και επίσης σχετίζεται με την ανάπτυξη ενδοτοξιναιμίας. Επίσης, το είδος της καταστολής που χρησιμοποιείται στις Μονάδες Εντατικής Θεραπείας (ΜΕΘ) έχει επίπτωση στη νοσηρότητα και τη θνητότητα των ασθενών. Η κλονιδίνη, ένας α2-αδρενεργικός αγωνιστής, που έχει χρησιμοποιηθεί τόσο περιεγχειρητικά όσο και για καταστολή στη ΜΕΘ, φαίνεται πως ασκεί προστατευτική δράση σε μοντέλα ισχαιμίας/επαναιμάτωσης. Σκοπός: Σκοπός της παρούσας μελέτης ήταν η εκτίμηση της επίδρασης της προχορήγησης κλονιδίνης στο οξειδωτικό φορτίο στο έντερο, το ήπαρ και τους πνεύμονες και στην ανάπτυξη ενδοτοξιναιμίας στην πυλαία και συστηματική κυκλοφορία σε επίμυες που υποβλήθηκαν σε σημαντικού βαθμού H/S. Υλικό και Μέθοδος: Η μελέτη πραγματοποιήθηκε σε 64 επίμυες και αποτελείται από δύο σκέλη: ένα για τον προσδιορισμό του οξειδωτικού φορτίου και ένα για τη μέτρηση της ενδοτοξίνης. Σε κάθε σκέλος, τα ζώα μοιράστηκαν σε 4 ομάδες: (1) ομάδα ελέγχου (Sham), όπου τα ζώα καθετηριάστηκαν χωρίς να πραγματοποιηθεί αφαίμαξη, (2) ομάδα H/S (H/S) και δύο ομάδες στις οποίες προχορηγήθηκε κλονιδίνη, (ομάδα 3,Clonidine) και (ομάδα 4, Clonidine-H/S). Το H/S, διάρκειας μίας ώρας, στόχευε σε τιμές μέσης αρτηριακής πίεσης 30-40mmHg και ολοκληρώθηκε με επαναχορήγηση του απολεσθέντος αίματος. Τρεις ώρες μετά την αναζωογόνηση, το οξειδωτικό φορτίο εκτιμήθηκε με δύο μεθόδους: (α) τη μέτρηση των οργανικών υδροϋπεροξειδίων (LOOHs) και (β) τη μέτρηση της ρίζας του υπεροξειδίου (O2.-) στο έντερο, στο ήπαρ και τους πνεύμονες ενώ για τη μέτρηση της ενδοτοξίνης, ελήφθησαν δείγματα αίματος από την πυλαία φλέβα και την αορτή. Αποτελέσματα: Οι επίμυες που υπεβλήθησαν σε H/S παρουσίασαν στατιστικά σημαντική αύξηση του οξειδωτικού φορτίου σε όλα τα όργανα. Η προχορήγηση κλονιδίνης προκάλεσε μείωση της παραγωγής LOOHs μετά από H/S στο έντερο (Ρ<0.001), στο ήπαρ (Ρ<0.05) και τους πνεύμονες (Ρ<0.05), σε σχέση με την ομάδα H/S. Επίσης, η ομάδα Clonidine-H/S παρουσίασε μειωμένο ρυθμό παραγωγής του O2.- σε σχέση με την ομάδα H/S, στο έντερο (P< 0.001), στο ήπαρ (P< 0.001) και τους πνεύμονες (Ρ<0.005). Τέλος, όσον αφορά τα επίπεδα ενδοτοξίνης, βρέθηκαν στατιστικά σημαντικά αυξημένα μετά από H/S τόσο στην πυλαία (Ρ<0.05), όσο και στη συστηματική (Ρ<0.001) κυκλοφορία, ενώ η προχορήγηση κλονιδίνης οδήγησε σε μείωση της ενδοτοξίνης και στις δύο κυκλοφορίες (πυλαια: Ρ<0.05 και συστηματική: Ρ<0.001) σε σχέση με την ομάδα H/S. Συμπέρασμα: Στην παρούσα μελέτη βρέθηκε για πρώτη φορά ότι η κλονιδίνη ασκεί αντιοξειδωτική δράση στο έντερο, στο ήπαρ και στους πνεύμονες όταν χορηγείται προ του H/S, το οποίο, ως γνωστόν, προκαλεί σημαντικού βαθμού OS σε αυτά τα όργανα. Μάλιστα, αυτό εκτιμήθηκε για πρώτη φορά σε μοντέλο H/S με την εφαρμογή μιας νέας άμεσης και ποσοτικής μεθόδου προσδιορισμού του O2.-. Τα αποτελέσματα αυτά αποκτούν ιδιαίτερη σημασία, καθώς το επαγόμενο από σοβαρή αιμορραγία OS ενέχεται στην παθογένεια του MODS (Multiple Organ Dysfunction Syndrome). Επιπλέον, η κλονιδίνη περιόρισε την επαγόμενη από το H/S ενδοτοξιναιμία, γεγονός που μπορεί να αποδοθεί, τουλάχιστον μερικώς στην αντιοξειδωτική της δράση στον εντερικό βλεννογόνο. Αυτή η παρατηρούμενη μείωση της ενδοτοξιναιμίας, ενδέχεται να συμβάλλει με τη σειρά της στο μειωμένο OS στα όργανα. Αν και τα αποτελέσματα πειραματικών μελετών σε ζώα δεν μπορούν πάντα να αναχθούν σε συμπεράσματα που αφορούν τους ανθρώπους, αυτή η μελέτη συνηγορεί υπέρ της χρήσης της κλονιδίνης σαν συμπληρωματικό αναισθητικό παράγοντα εκλογής σε ασθενείς επιρρεπείς σε απώλεια αίματος, με στόχο την άμβλυνση των παθοφυσιολογικών επιπτώσεων του H/S που μπορούν να οδηγήσουν σε MODS. / Hemorrhagic shock (H/S) leads to the development of oxidative stress (OS) as a result of the excessive production of reactive oxygen species (ROS) in various tissues during reperfusion. Likewise, ischemia and ROS are believed to compromise the integrity of the intestinal barrier, resulting in endotoxemia. Moreover, it is now clear that the choice of sedation in ICU (Intensive Care Unit) patients affects their outcome. The a2-adrenergic agonist clonidine that is used as an adjunct to anesthesia, as well as in the ICU setting, has been shown to exert protective effects in models of ischemia/reperfusion injury. Aim of the study: To test the effect of clonidine pre-treatment of rats in the H/S-induced OS in the gut, liver and lung tissues and endotoxemia as well. Materials and Methods: The study consisted of two arms (64 rats): one for the measurement of the oxidative load in the organs and one for the measurement of endotoxin. Four animal groups (n=8 per group) were used for each arm (Sham, Clonidine, H/S and Clonidine-H/S group). The duration of Η/S was one hour, targeting to a mean arterial pressure of 30-40mmHg, at the end of wich rats were rescusitated by reinfusion of the shed blood. Three hours after rescusitation, the oxidative load was estimated with the measurement of lipid hydroperoxides (LOOHs) and superoxide radical (O2.- ) production in the liver, gut and lungs of the animals, while the levels of endotoxin were determined in both the systemic and portal circulation. Results: Rats subjected to H/S exerted increase in the oxidative load in all the tested organs. Clonidine pre-treatment resulted in a statistically significant reduction of LOOHs production after H/S in the gut (P < 0.001), liver and lungs of the rat (P < 0.05). Rats in the Clonidine-H/S group exhibited a statistically significant reduction (P< 0.001) in the production of O2.- in the gut and liver, and to a lesser extent in the lungs ( P < 0.05) compared to H/S group. H/S induced endotoxemia in the portal and systemic circulation, whereas clonidine pre-treatment reduced the amount of endotoxin detected both in the portal (P<0.05) and systemic (P<0.01) circulation compared to H/S. Conclusion: This study documents for the first time that clonidine pre-treatment prior to H/S results in a significant reduction of the OS observed in the gut, liver and lungs of the rat. Moreover, this antioxidant effect was estimated for the first time in a model of H/S with a new, direct and quantitative method of O2.- production. These results are of great value, since the H/S-induced OS is implicated in the pathogenesis of MODS (Multiple Organ Dysfunction Syndrome). Furthermore, clonidine prevented H/S induced endotoxemia in both portal and systemic circulations, probably due to its antioxidant effect on the intestinal epithelium. The reduced endotoxemia after clonidine pre-treatment may contribute to the decreased OS observed in the liver and lungs. Although laboratory results on animals should not be easily extrapolated to humans, we believe that clonidine merit consideration as an adjunctive sedative agent of choice in patients susceptible to develop H/S, as it may prevent the development of MODS, improving likewise their outcome.

Introdução: Cistite Hemorrágica (CH) é uma grave complicação do Transplante de Células-Tronco Hematopoiéticas (TCTH) Alogênico. Sua incidência varia de 12 a 25,5%. A forma precoce desenvolve-se devido aos efeitos tóxicos de certos quimioterápicos usados no regime de condicionamento, especialmente Ciclofosfamida. Já a CH tardia ocorre a partir do terceiro dia após o TCTH e sua etiologia é multifatorial. Vários fatores de risco para o desenvolvimento de CH tardia foram descritos, incluindo Doença do Enxerto Contra o Hospedeiro (DECH) aguda, doador não relacionado, infecções por vírus urotrópicos, sexo masculino e condicionamento mieloablativo. Materiais e Métodos: O presente estudo tem como objetivos descrever a incidência de CH em pacientes adultos e pediátricos submetidos a TCTH alogênico e identificar fatores de risco associados ao desenvolvimento de CH nesta população. Foram analisados dados de prontuário de 347 pacientes submetidos a TCTH Alogênico no Hospital de Clínicas de Porto Alegre no período de Janeiro de 2001 a Dezembro de 2014. Resultados: CH ocorreu em 42 pacientes (12,1%, IC: 8,9 - 16%), em uma média de 53.4 dias após o procedimento (desvio padrão: 28.1 dias). Apenas 1 paciente (2,4%) desenvolveu CH precoce, com início dos sintomas no D+1. Entre os 41 pacientes que desenvolveram CH tardia, BK vírus foi o principal agente viral identificado. CH ocorreu em 12.8% dos pacientes que receberam condicionamento mieloablativo e em 10.5% dos restantes (P = 0,704). Dos 197 pacientes que apresentaram DECH aguda, 35 (17,8%) desenvolveram CH e somente 7 (4,9%) apresentaram CH na ausência de DECH aguda (P < 0,001). CH foi mais frequente também em pacientes do sexo masculino (P = 0,027). Conclusão: A incidência de CH em nossa amostra foi semelhante à encontrada em outros trabalhos. DECH aguda e sexo masculino estiveram associados a um maior risco de desenvolvimento de CH. / Introduction: Hemorrhagic cystitis (HC) is a serious complication of Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) afecting 12 to 25.5% of the patients. The early-onset form of HC develops during or until 72 hours after the conditioning regimen containing high doses of certain chemotherapy drugs such as Busulfan and especially Cyclophosphamide. Late-onset HC occurs from the third day on after HSCT and its etiology is multifactorial. Several risk factors for the late-onset form have been reported including graft-versus-host disease (GVHD), unrelated donor, urotropic infections, male gender and myeloblative conditioning regimen. Methods: This study aims to evaluate the incidence of HC in adult and pediatric patients undergoing Allogeneic HSCT and to identify risk factors associated with the development of HC in this population. Medical records of 347 patients who underwent Allogeneic HSCT at Hospital de Clínicas, Porto Alegre, Brazil, from January 2001 to December 2014 were analyzed. Results: HC occurred in 42 patients (12.1% CI: 8.9 - 16%) at an average of 53.4 days after the procedure (standard deviation: 28.1 days). Only one of them developed early-onset HC, with onset of symptoms on D+1. Among the 41 patients who developed late-onset HC, BKV was the main identified viral agent. HC developed in 12.8% of the patients treated with myeloablative conditioning and in 10.5% of the remaining patients (P = 0.704). Of the 197 patients with acute GVHD, 35 (17.8%) developed HC and only 7 (4.9%) showed HC in the absence of GVHD (P<0.001). HC was also more frequent in males than females (P = 0.027). Conclusion: The incidence of HC in our sample was similar to that found in other studies. In our cohort of patients being male and having acute GVHD increased the risk of developing HC.

Este trabalho teve como objetivo avaliar os efeitos sistêmicos, microcirculatórios assim como mudanças na expressão gênica renal, causados pela ação da noradrenalina, nitropussiato de sódio e levosimendan no tratamento do choque hemorrágico. Nesse estudo foi utilizado o modelo da câmara dorsal.Os animais foram sujeitos a choque hemorrágico e após, foram aleatoriamente divididos em quatro grupos. Os grupos foram: CTRL, recebeu apenas ringer lactato; NPS recebeu ringer lactato com nitroprussiato de sódio; NA recebeu ringer lactato com noradrenalina e LEV, recebeu ringer lactato com levosimendan. Foram avaliados parâmetros sistêmicos, assim como parâmetros microcirculatórios (comparados como percentual em relação ao momento basal). Além disso, foi avaliada a expressão gênica renal de eNOS, HIF-1&#945;, ICAM e caspase-3. O grupo NPS apresentou uma recuperação sustentada do diâmetro arteriolar ( 89 12 %) e DCF (125 114 %) ao final do tratamento. Houve recuperação da velocidade de hemácias nos grupos CTRL e NPS. Não houve diferença em relação ao número de leucócitos aderidos e/ou rolantes ao final do tratamento. A expressão gênica renal de eNOS e caspase-3 entre os grupos não apontou diferenças, entretanto houve diferença significativa na expressão renal de HIF- 1&#945; no grupo NA (0,65 0,08, UA) em relação ao grupo CTRL (0,44 0,06, UA) e LEV (0,45 0,06, UA). Todos os grupos tiveram uma maior expressão de ICAM (0,65 0,12; 0,7 0,12; 0,069 0,06; 0,65 0,12, UA) em relação ao grupo SHAM (0,50 0,05, UA). Ringer lactato puro ou associado com noradrenalina ou levosimendan não foram suficientes para recuperar e sustentar os parâmetros microvasculares. O tratamento com nitroprussiato de sódio foi o que apresentou os melhores resultados, com recuperação dos diâmetros arteriolar, da DCF e velocidade de hemácias. / This work aimed at evaluating the systemic and microcirculatory effects, as well as changes in renal gene expression elicited by noradrenalin, sodium nitroprusside and levosimendan associated to volume resuscitation in the treatment of hemorrhagic shock. The dorsal chamber model was used in this study. Animals were subjected to hemorrhagic shock and after that, were randomly distributed between four groups. Groups were: CTRL, received only lactated ringer's solution; NPS received lactated ringer's solution with sodium nitroprusside; NA received lactated ringer's solution with noradrenaline and LEV received lactated ringer's with levosimendan. Systemic and microcirculatory parameters were evaluated ( as percent change compared to baseline). Furthermore, renal genic expression of eNOS, HIF-1a and caspase-3 were also evaluated. NPS group presented a sustained recovery of arteriolar diameter ( 89 12 %) and FCD (125 114 %) at the end of the treatment. There was a red blood cell velocity recovery in CTRL and NPS groups. There was no difference regarding adhered or rolling leukocytes at the end of the treatment. eNOS and caspase-3 renal genic expression between groups showed no differences, however, there was a significant difference in renal genic expression of HIF-1&#945; in NA group (0,65 0,08, AU) compared to CTRL (0,44 0,06, AU) e LEV (0,45 0,06, AU). All groups had a higher expression of ICAM (0,65 0,12; 0,7 0,12; 0,069 0,06; 0,65 0,12, AU) compared to the SHAM group (0,50 0,05, AU). Ringer's lactate solution associated or not to noradrenaline or levosimendan were not enough to recover and sustain microvascular parameters. Treatment with sodium nitroprusside presented the best results, with sustained arteriolar diameter, FCD and RBCV recoveries.