A fatal and metabolic experimental hemorrhagic shock in immature swine

Abstract Purpose: To use blood lactate (BL) as an end-point metabolic marker for the begin resuscitation of volume replacement in experimental hemorrhagic shock. Methods: Group I (n=7) was not bled (Control). Animals in Group II (n=7) were bled to a MAP of 30mmHg in thirty minutes. Hemodynamic and metabolic data were recorded at Baseline, at 30, 60 and 120 minutes after Baseline. The animals were intubated in spontaneous breathing (FIO2=0.21) with halothane. Results: Group I all survived. In Group II all died; no mortality occurred before a BL<10mM/L. Beyond the end-point all animals exhibited severe acidemia, hyperventilation and clinical signs of shock. Without treatment all animals died within 70.43±24.51 min of hypotension shortly after reaching an average level of BL 17.01±3.20mM/L. Conclusions: Swine's breathing room air spontaneously in hemorrhagic shock not treated a blood lactate over 10mM/L results fatal. The predictable outcome of this shock model is expected to produce consistent information based on possible different metabolic and hemodynamic patterns as far as the type of fluid and the timing of resuscitation in near fatal hemorrhagic shock.

Cardiovascular Effects of Shock and Trauma in Experimental Models. A Review

Abstract Experimental models of human pathology are useful guides to new approaches towards improving clinical and surgical treatments. A systematic search through PubMed using the syntax (shock) AND (trauma) AND (animal model) AND (cardiovascular) AND ("2010/01/01"[PDat]: "2015/12/31"[PDat]) found 88 articles, which were reduced by manual inspection to 43 entries. These were divided into themes and each theme is subsequently narrated and discussed conjointly. Taken together, these articles indicate that valuable information has been developed over the past 5 years concerning endothelial stability, mesenteric lymph, vascular reactivity, traumatic injuries, burn and sepsis. A surviving interest in hypertonic saline resuscitation still exists.

Enhanced cyclooxygenase-2 activity leads to intestinal dysmotility following hemorrhagic shock

ABSTRACT PURPOSE: To test whether hemorrhagic shock (HS) increases the Cyclooxygenase-2 (COX-2) expression in the intestine and whether this enhanced COX-2 expression mediates the intestinal dysmotility after HS. METHODS: Male Wistar rats were randomly divided into HS sham group and HS group. At 180 min following HS establishment, the duodenum samples were harvested to assess the motility function, protein expression of COX-2 and the downstream products of COX-2, prostaglandins. RESULTS: Examination of motility function ex vivo showed that the contractile response to acetylcholine of smooth muscle strips of rats subjected to HS was significantly suppressed. A COX-2 inhibitor, NS-398, abolished this depressed contractile response after HS. Western blotting revealed an increased protein expression of COX-2 in intestinal tissues of HS rats. Immunohistochemical examination indicated that intestine tissues of HS rats were manifested by part of villous expansion and disruption, a large amount of COX-2 positive cells appearance in lamina propria and submucosa. Furthermore, the contents of prostaglandin E2 was significantly increased in intestinal tissues of HS rats. CONCLUSION: The enhanced COX-2/ prostaglandin E2 involves in the hemorrhagic shock induced intestinal dysmotility.

Post-hemorrhagic shock mesenteric lymph is an important contributor to cardiac dysfunction following hemorrhagic shock

PURPOSE: To evaluate whether post-hemorrhagic shock mesenteric lymph (PSML) is involved in cardiac dysfunction induced by hemorrhagic shock. METHODS: The hemorrhagic shock model (40±2 mmHg, 3h) was established in rats of the shock and shock+drainage groups; and PSML drainage was performed from hypotension 1-3h in the shock+drainage rats. Then, the isolated hearts were obtained from the rats for the examination of cardiac function with Langendorff system. Subsequently, the isolated hearts were obtained from normal rats and perfused with PSML or Krebs-Henseleit solution, and the changes of cardiac function were observed. RESULTS: The left ventricular systolic pressure (LVSP) and the maximal rates of LV developed pressure (LVDP) rise and fall (±dP/dt max) in the shock and shock+drainage groups were lower than that of the sham group; otherwise, these indices in the shock+drainage group were higher compared to the shock group. In addition, after isolated hearts obtained from normal rats perfusing with PSML, these cardiac function indices were gradual decline along with the extension of time, such as heart rate, LVSP, ±dP/dt max, etc. CONCLUSION: Post-hemorrhagic shock mesenteric lymph is an important contributor to cardiac dysfunction following hemorrhagic shock. .

Myosin light chain kinase is necessary for post-shock mesenteric lymph drainage enhancement of vascular reactivity and calcium sensitivity in hemorrhagic-shocked rats

Vascular hyporeactivity is an important factor in irreversible shock, and post-shock mesenteric lymph (PSML) blockade improves vascular reactivity after hemorrhagic shock. This study explored the possible involvement of myosin light chain kinase (MLCK) in PSML-mediated vascular hyporeactivity and calcium desensitization. Rats were divided into sham (n=12), shock (n=18), and shock+drainage (n=18) groups. A hemorrhagic shock model (40±2 mmHg, 3 h) was established in the shock and shock+drainage groups. PSML drainage was performed from 1 to 3 h from start of hypotension in shock+drainage rats. Levels of phospho-MLCK (p-MLCK) were determined in superior mesenteric artery (SMA) tissue, and the vascular reactivity to norepinephrine (NE) and sensitivity to Ca2+ were observed in SMA rings in an isolated organ perfusion system. p-MLCK was significantly decreased in the shock group compared with the sham group, but increased in the shock+drainage group compared with the shock group. Substance P (1 nM), an agonist of MLCK, significantly elevated the decreased contractile response of SMA rings to both NE and Ca2+ at various concentrations. Maximum contractility (Emax) in the shock group increased with NE (from 0.179±0.038 to 0.440±0.177 g/mg, P<0.05) and Ca2+ (from 0.515±0.043 to 0.646±0.096 g/mg, P<0.05). ML-7 (0.1 nM), an inhibitor of MLCK, reduced the increased vascular response to NE and Ca2+ at various concentrations in the shock+drainage group (from 0.744±0.187 to 0.570±0.143 g/mg in Emax for NE and from 0.729±0.037 to 0.645±0.056 g/mg in Emax for Ca2+, P<0.05). We conclude that MLCK is an important contributor to PSML drainage, enhancing vascular reactivity and calcium sensitivity in rats with hemorrhagic shock.

Role of protein kinase G on the post-shock mesenteric lymph blockage ameliorating vascular calcium sensitivity

PURPOSE: To investigate the role of protein kinase G (PKG) in blocking post-shock mesenteric lymph (PSML) return ameliorating the calcium sensitivity in hemorrhagic shock rats. METHODS: Male Wistar rats were randomly divided into sham, shock, shock+ligation (shock plus mesenteric lymph duct ligation (MLDL)), shock+drainage (shock plus PSML drainage) groups. After shock (hypotension 40mmHg) for three hours or corresponding times, the superior mesenteric artery (SMA) was taken out for detecting the PKG and phospho PKG (p-PKG) contents, and the vascular rings of SMA were prepared for assaying the calcium sensitivity using an isolated organ perfusion system. RESULTS: The PKG and p-PKG contents of SMA in shock group were significantly increased than that of sham group, and MLDL or PSML drainage reducing the levels of PKG and p-PKG. Meanwhile, the vascular calcium sensitivity in shock group was significantly lower than that of sham group, MLDL or PSML drainage enhanced the calcium sensitivity. After incubating with PKG regulators in shock+ligation and shock+drainage groups, the PKG agonist 8Br-cGMP reduced the contractility of vascular rings to gradient calcium ions and Emax and the PKG inhibitor agonist KT5823 elevated the calcium sensitivity significantly. CONCLUSION: Protein kinase G plays an important role in post-shock mesenteric lymph blockage improving vascular calcium sensitivity.

Modelo experimental de choque hemorrágico não controlado em porcos / Experimental model of non-controlled hemorrhagic shock in pigs / Modelo experimental de choque hemorrágico no controlado en cerdos

JUSTIFICATIVA E OBJETIVOS: Uma compreensão melhor das alterações fisiopatológicas associadas ao trauma e ao choque hemorrágico pode ajudar no desenvolvimento de terapêuticas capazes de reduzir a mortalidade relacionada ao trauma. O objetivo deste estudo é descrever um modelo de choque hemorrágico não controlado em porcos. MÉTODOS: Como medicação pré-anestésica, os animais receberam cetamina e midazolan. A anestesia foi induzida com propofol e a intubação traqueal foi realizada na vigência de respiração espontânea. Após a intubação, realizou-se bloqueio neuromuscular. Os animais foram mantidos em respiração mecânica controlada e normocapnia. A anestesia foi mantida com propofol e fentanil, de acordo com a necessidade. Solução de soro fisiológico 0,9 por cento foi infundida em todo o período de preparação. MONITORAÇÃO: Foram utilizados cardioscópio, oxímetro de pulso, medida de pressão arterial invasiva, cateter volumétrico de artéria pulmonar e medida de débito urinário por cistostomia. Modelo experimental: após registro inicial de variáveis hemodinâmicas, metabólicas e de coagulação, realizaram-se incisão subcostal direita e biópsia hepática do lobo esquerdo. A infusão de anestésicos foi reduzida, enquanto a de solução de salina isotônica interrompida. Uma incisão de 12 cm de extensão por 2 cm de profundidade foi feita no lobo hepático direito, seguida de divulsão digital do ferimento. Durante a fase de hemorragia, uma sonda de aspiração foi posicionada junto ao ferimento e o volume de sangue aspirado foi registrado. Quando a pressão arterial média chegou a 40 mmHg e o sangramento foi superior a 700 mL, pôde ser iniciada a fase de intervenção de acordo com o tipo de estudo. CONCLUSÃO: É importante continuar o desenvolvimento de modelos experimentais com o objetivo final de reduzir a alta mortalidade e os custos associados ao trauma.

BACKGROUND AND OBJECTIVES: A better understanding of pathophysiologic changes associated to trauma and hemorrhagic shock can help the development of therapies capable of reducing trauma-related mortality. The objective of this study was to describe a model of non-controlled hemorrhagic shock in pigs. METHODS: Animals received ketamine and midazolam as pre-anesthetic medications. Anesthesia was induced with propofol, and tracheal intubation was performed with the animals on spontaneous ventilation. After intubation neuromuscular blockade was performed. Animals were maintained in controlled mechanical ventilation and normocapnia. Anesthesia was maintained with propofol and fentanyl as needed. Saline was infused during the entire preparation period. MONITORING: Cardioscope, pulse oximeter, invasive blood pressure, volumetric catheter in the pulmonary artery, and urine output by cystostomy were used. Experimental model: after the initial recording of hemodynamic, metabolic, and coagulation variables, right subcostal incision and left lobe liver biopsy were performed. Anesthetic infusion was reduced while the infusion of saline was interrupted. An incision 12 cm long 2 cm deep was performed in the right liver lobe followed by digital divulsion of the wound. During the hemorrhagic phase, an aspiration probe was placed close to the wound and the volume of aspirated blood was recorded. When mean arterial pressure reached 40 mmHg and bleeding was above 700 mL the intervention phase was initiated according to the type of study. CONCLUSION: The development of experimental models to reduce high mortality and costs related to trauma is important.

JUSTIFICATIVA Y OBJETIVOS: Una comprensión mejor de las alteraciones fisiopatológicas asociadas al trauma y al choque hemorrágico, puede ayudar en el desarrollo de las terapéuticas capaces de reducir la mortalidad relacionada con el trauma. El objetivo de este estudio es describir un modelo de choque hemorrágico no controlado en cerdos. MÉTODOS: Como medicación preanestésica, los animales recibieron cetamina y midazolan. La anestesia fue inducida con propofol, y la intubación traqueal fue realizada con la respiración espontánea. Después de la intubación, se realizó el bloqueo neuromuscular. Los animales se mantuvieron bajo respiración mecánica controlada y normocapnia. La anestesia se mantuvo con propofol y fentanil, a tono con la necesidad. Una solución de suero fisiológico al 0,9 por ciento fue infundida durante todo el período de la preparación. MONITOREO: Se usaron el cardioscopio, oxímetro de pulso, medida de presión arterial invasiva, catéter volumétrico de arteria pulmonar y medida de débito urinario por cistostomía. Modelo experimental: después del registro inicial de las variables hemodinámicas, metabólicas y de coagulación, se realizaron la incisión subcostal derecha y la biopsia hepática del lóbulo izquierdo. La infusión de anestésicos fue reducida, mientras que la solución de salina isotónica se interrumpió. Una incisión de 12 cm de extensión por 2 cm de profundidad se hizo en el lóbulo hepático derecho, seguida de una divulsión digital de la herida. Durante la fase de hemorragia, una sonda de aspiración fue posicionada junto a la herida, y el volumen de sangre aspirado fue registrado. Cuando la presión arterial promedio llegó a 40 mmHg y el sangramiento fue superior a 700 mL, pudo iniciarse la fase de intervención de acuerdo con el tipo de estudio. CONCLUSIÓN: Es importante continuar desarrollando modelos experimentales con el objetivo final de reducir la alta mortalidad y los costes asociados al trauma.

Fisiopatología del shock: Nuevas perspectivas / Pathophysiology of shock: New perspectives

La actividad metabólica puede modificarse mediante la regulación de la población mitocondrial en distintas enfermedades críticas. A través de observaciones y ensayos clínicos examinamos esta adaptación metabólica en el shock cardiogénico, hemorrágico y séptico. La caída de la disponibilidad de O2 (DO2) llevaría a una reducción de la población mitocondrial y consecuentemente a una disminución del consumo de O2 (VO2). Esta secuencia permite atenuar y aun evitar la adquisición de una deuda de O2, considerada hasta hoy base fundamental de la fisiopatología del shock. El costo de esta adaptación mitocondrial es menor energía disponible y el déficit energético resultante ha sido relacionado con la falla orgánica múltiple (FOM), importante complicación de diversos procesos inflamatorios agudos y estados de shock. La FOM es mejor tolerada que el metabolismo anaeróbico y es potencialmente reversible si se revierten las causas desencadenantes y se reestablece el nivel energético por medio de la biogénesis mitocondrial.El desacople de la fosforilación oxidativa mitocondrial ocurre tanto en diversos modelos experimentales de shock como así también en el shock séptico en el hombre. Esta alteración mitocondrial puede ser detectada por un aumento desmesurado del VO2 en respuesta al incremento terapéutico de la DO2. Este aumento de la actividad metabólica puede ser equívocamente interpretado como la fase de repago de una deuda de O2.

Metabolic activity can be down-regulated throughout the reduction of mitochondrial population. Lowering O2 demand in cardiogenic, hemorrhagic and septic shock is here examined through clinical observations and trials. A decrease in the availability of O2 will be followed by reductions in mitochondrial population and, therefore, in a decrease in O2 demand. This response may lessen or prevent the acquisition of an O2 debt; until now, cornerstone in the pathophysiology of shock. The cost of this adaptation is less energy production, and the resulting energy deficit has been linked to multiple organ failure (MOF), a complication of acute inflammatory processes and shock. MOF is better tolerated than anaerobic metabolism and is potentially reversible if the triggering causes are reversed and the energy level is re-established through mitochondrial biogenesis.Decoupling of mitochondrial oxidative phosphorylation occurs in both experimental models and in clinical septic shock. In critical patients this phenomenon may be detected by an inordinate increase in VO2 in response to a therapeutically increased DO2. This hipermetabolic stage can be mistakenly interpreted as the repayment phase of an O2 debt.

Shock hemorrágico / Hemorrhagic shock

El shock hemorrágico es la principal causa de muerte en el trauma, la principal causa de muertes potencialmente prevenible y una de las principales causas de muerte en la población menor de 44 años. La hemorragia masiva puede producir inestabilidad hemodinámica, disminución de la perfusión tisular, daño de órganos y muerte. Los principales objetivos de la resucitación son restaurar el volumen sanguíneo circulante y detener la hemorragia, mientras se activan los protocolos de manejo de la hemorragia masiva. Si bien el método óptimo de resucitación no ha sido claramente establecido, el uso de fluidos intravenosos y productos sanguíneos son elementos esenciales del manejo. Los defectos hemostáticos son frecuentes en la hemorragia masiva y evolucionan rápidamente. Se recomienda el uso precoz de plasma fresco congelado y plaquetas para prevenir el mecanismo dilucional de la coagulopatía, y el manejo agresivo de ésta una vez establecida. Finalmente, el manejo posterior a la emergencia incluye los cuidados intensivos para una monitorización estricta y el manejo de las eventuales complicaciones sistémicas, como la falla multiorgánica.

Hemorrhagic shock is the leading cause of death after injury, the major cause of potentially preventable deaths and one of the leading cause of death in young people. Massive hemorrhage may lead to hemodynamic instability, decreased tissue perfusion, organ damage, and death. The main goals of resuscitation are to restore circulating blood volume and to stop the source of hemorrhage, while the major hemorrhage protocols must be immediately declare. Although the optimal method of resuscitation has not been clearly established, the use of intravenous fluids and blood products are the key aspects of the management. The haemostatic defects are common in massive hemorrhage and trauma, and are likely to evolve rapidly. The early use of fresh frozen plasma and platelets is recommended to prevent the dilutional mechanism, and if the haemosthatic defect is established, it should be aggressively treated. Finally, further management includes intensive therapy to closely monitoring and management of any systemic complications, as multiorganic organ damage.

Vasodilation increases pulse pressure variation, mimicking hypovolemic status in rabbits

OBJECTIVE: To test the hypothesis that pulse pressure respiratory variation (PPV) amplification, observed in hypovolemia, can also be observed during sodium nitroprusside (SNP)-induced vasodilation. INTRODUCTION: PPV is largely used for early identification of cardiac responsiveness, especially when hypovolemia is suspected. PPV results from respiratory variation in transpulmonary blood flow and reflects the left ventricular preload variations during respiratory cycles. Any factor that decreases left ventricular preload can be associated with PPV amplification, as seen in hypovolemia. METHODS: Ten anesthetized and mechanically ventilated rabbits underwent progressive hypotension by either controlled hemorrhage (Group 1) or intravenous SNP infusion (Group 2). Animals in Group 1 (n = 5) had graded hemorrhage induced at 10 percent steps until 50 percent of the total volume was bled. Mean arterial pressure (MAP) steps were registered and assumed as pressure targets to be reached in Group 2. Group 2 (n = 5) was subjected to a progressive SNP infusion to reach similar pressure targets as those defined in Group 1. Heart rate (HR), systolic pressure variation (SPV) and PPV were measured at each MAP step, and the values were compared between the groups. RESULTS: SPV and PPV were similar between the experimental models in all steps (p > 0.16). SPV increased earlier in Group 2. CONCLUSION: Both pharmacologic vasodilation and graded hemorrhage induced PPV amplification similar to that observed in hypovolemia, reinforcing the idea that amplified arterial pressure variation does not necessarily represent hypovolemic status but rather potential cardiovascular responsiveness to fluid infusion.

Embolia de líquido amniótico: Criterio diagnóstico en dos casos fatales / Amniotic fluid embolism: Diagnostic criteria in two fatal cases

La embolia de líquido amniótico continúa siendo una causa importante de mortalidad materna. Presentamos la información obtenida por medio de la cateterización cardíaca derecha y la ecocardiografía, en dos pacientes que desarrollaron embolia de líquido amniótico y fallecieron por shock y coagulación intravascular diseminada a pesar del tratamiento intensivo. Aunque la fisiopatología continúa siendo discutida, la embolia por líquido amniótico se puede diagnosticar y manejar a partir de los valores hemodinámicos y el ecocardiograma.

Amniotic fluid embolism still remains an important cause of maternal mortality. We present information obtained by echocardiography and right cardiac catheterization of two patients who developed amniotic fluid embolism and died from shock and disseminated intravascular coagulation despite intensive medical treatment. Although the pathophysiology remains controversial, amniotic fluid embolism can be presumptively diagnosed and managed with hemodynamic values and echocardiography.

Responsiveness to different volume therapies following hemodilution and hemorrhagic shock: a comparative experimental study in rats

Guidelines for volume replacement for acutely hemorrhaged and hemodiluted trauma patients have not been well established. Purpose: To evaluate the effects of acute hemodilution on mean arterial pressure (MAP), and responsiveness of acutely hemodiluted and subsequently hemorrhaged rats to different volume therapies. Methods: 180 rats were hemodiluted to simulate hemorrhaged trauma patients with persistent bleeding after high volume replacement with isotonic solutions. Thirty hemodiluted [Anemia (ANE) group] animals received no further treatment. The remaining 150 animals were subjected to hypovolemic shock and randomized into five groups, according to the treatment option employed: Control (CTL) animals did not receive subsequent treatment after hemorrhagic hypovolemia, SAL4 animals received isotonic saline 4 mL/kg, SAL32 animals received isotonic saline 32 mL/kg, HS animals received hypertonic saline 4 mL/kg and BLD animals received re-infusion of drawn blood. Results: Highest mean arterial pressure (MAP) was achieved by BLD, followed by SAL32 and HS. MAP after treatment of BLD, HS, SAL32 and ANE were higher than CTL (p=0.036). At 85 and 95 minutes of experiment, SAL4, SAL32 and HS presented the lowest hematocrit levels (p<0.01). At day 3, ANE, CTL and HS had the highest hematocrit. SAL4 and CTL groups presented the highest mortality rates. Conclusion: Hypertonic saline is an effective and safe initial therapy for hemodiluted rats undergoing hemorrhagic shock, with an overall outcome comparable to blood replacement or high volume isotonic saline administration.

A conduta para reposição volêmica em pacientes traumatizados, hemodiluídos não está bem estabelecida. Objetivo: Avaliar o efeito da hemodiluição sobre a pressão arterial média (PAM), bem como a resposta de ratos agudamente hemodiluídos e submetidos a choque hemorrágico, à reanimação com diferentes soluções. Métodos: 180 ratos foram hemodiluídos, simulando pacientes traumatizados com sangramento persistente após reposição com soluções isotônicas. Trinta ratos hemodiluídos (grupo ANE) foram observados, sem tratamento. Os demais 150 foram submetidos a choque hipovolêmico e randomizados em 5 grupos segundo a opção terapêutica: CTL (controle), sem tratamento subseqüente após hipovolemia hemorrágica; SAL4 que recebeu 4 mL/kg de salina isotônica; SAL32 que recebeu 32 mL/kg de salina isotônica ; SH que recebeu 4mL/kg de salina hipertônica; e BLD que recebeu reinfusão do sangue removido. Resultados: A pressão arterial média (PAM) mais alta ocorreu no grupo BLD, seguida pelo SAL32, e SH. A PAM após tratamento nos grupos BLD, SH, SAL32 e ANE foram maiores que no CTL (-=0.036). Aos 85 e 95 minutos do experimento, SAL4, SAL32, e SH apresentaram os menores hematócritos (p<0.01). No 3° dia, ANE, CTL e SH apresentaram os maiores hematócritos. SAL4 e CTL apresentaram as maiores taxas de mortalidade. Em conclusão, nossos resultados indicam que a SH é uma terapia inicial efetiva e segura em ratos hemodiluídos, submetidos a hemorrágico choque, com prognóstico comparável à reposição com sangue ou administração de grande volume de solução isotônica.

Gender and sex hormones influence the response to trauma and sepsis: potential therapeutic approaches

Several clinical and experimental studies have demonstrated gender dimorphism in immune and organ responsiveness and in the susceptibility to and morbidity from shock, trauma, and sepsis. In this respect, cell-mediated immune responses have been shown to be depressed in males following trauma-hemorrhage, whereas they were aintained/enhanced in proestrus females. Furthermore, sex hormones have been shown to be responsible for this gender-specific immune response following adverse circulatory conditions. More specifically, studies indicate that androgens produce immunodepression following trauma-hemorrhage in males. In contrast, female sex steroids appear to exhibit immunoprotective properties following trauma and severe blood loss. With regard to the underlying mechanisms, receptors for sex hormones have been identified on various immune cells suggesting direct effects of these hormones on the immune cells. Alternatively, indirect effects of sex hormones, ie, modulation of cardiovascular responses or androgen- and estrogen-synthesizing enzymes, might contribute to gender-specific immune responses. Recent studies indicate that sex hormones, eg, dehydroepiandrosterone (DHEA), also modulate the function of peripheral blood mononuclear cells in surgical patients. Thus, the immunomodulatory properties of sex hormones/receptor antagonists/sex steroid synthesizing enzymes following trauma-hemorrhage suggests novel therapeutic strategies for the treatment of immunodepression in surgical patients.

Uma série de estudos clínicos e experimentais demonstram a existência de dimorfismo sexual das respostas imunológicas e orgânicas, bem como da suscetibilidade e morbidade em relação ao choque, ao trauma e à sepse. Respostas imunes celularmente mediadas apresentam-se deprimidas em machos em resposta ao binômio trauma-hemorragia, mas conservados/enaltecidos em fêmeas em proestro. Adicionalmente demonstra-se que os hormônios sexuais são responsáveis por esta dicomotomia de resposta sexualmente específica, em condições cardiovasculares adversas. Estudos específicos indicam que os andrógenos produzem imunodepressão pós-trauma hemorragia em machos. Em contraste, esteróides sexuais femininos parecem exibir propriedades imunoprotetoras após episódios de trauma com ou sem perda importante de sangue. No terreno dos mecanismos subjacentes, foram identificados receptores para hormônios sexuais em várias células do sistema imunológico, sugerindo a existência de efeitos diretos destes hormônios sobre tais células. Alternativamente, observam efeitos indiretos de hormônios sexuais tais como modulação das respostas cardiovasculares das enzimas sintetizadores de andrógeno e estrógeno, que podem contribuir para as estas respostas sexualmente diferenciadas. Estudos recentes indicam que os hormônios sexuais, como por exemplo a dehidroepiandrosterona também modulam a função de células mononucleares da série branca em pacientes cirúrgicos. Assim, as propriedades imunomodulatórias de hormônios sexuais/antagonistas de receptores/enzimas sintetizadores de esteróides após a ocorrência de trauma ou de hemorragia sugerem o caminho para novas estratégias terapêuticas para o tratamento de imunodepressão em pacientes cirúrgicos.

Indução anestésica após o tratamento do choque hemorrágico: estudo experimental comparando a cetamina e o etomidato / Anesthetic induction after treated hemorrhagic shock: experimental study comparing ketamine and etomidate

JUSTIFICATIVA E OBJETIVOS: O sangramento que leva ao choque hemorrágico geralmente necessita tratamento cirúrgico sob anestesia geral. Por sua vez, os anestésicos podem comprometer ainda mais as condições hemodinâmicas. O objetivo deste estudo foi o de comparar os efeitos hemodinâmicos da cetamina e do etomidato durante a indução anestésica em cães submetidos a um modelo experimental de choque hemorrágico e reanimação. MÉTODO: Trinta e dois cães mestiços foram submetidos ao choque hemorrágico pressão-controlado, reanimação e indução anestésica. Após atingir a pressão alvo de 40 mmHg eles foram divididos aleatoriamente em dois grupos de acordo com a solução usada na reanimação: NaCl a 0.9 por cento (32 ml.kg-1) e NaCl a 7,5 por cento (4 mL.kg-1). Após a infusão de volume, esses grupos foram divididos novamente de acordo com o anestésico utilizado: GI) NaCl a 0.9 por cento e cetamina; GII) NaCl a 7.5 por cento e cetamina; GIII) NaCl a 0.9 por cento e etomidato; e GIV) NaCl a 7.5 por cento e etomidato. Medições hemodinâmicas foram obtidas em cinco momentos: (M0) inicial; (M1) após o desenvolvimento do choque hemorrágico; (M2) após a administração de fluidos; (M3) 5 minutos após a indução anestésica; (M4) 15 minutos após a indução anestésica. Foi feita a análise estatística usando o teste t de Student e two-way ANOVA. Foram considerados significativos valores de p menores do que 0,05. RESULTADOS: Após a instalação do choque, ambas as soluções restabeleceram os padrões hemodinâmicos aos valores iniciais. Independente do anestésico ou da solução utilizados, após a indução anestésica a pressão arterial média permaneceu inalterada em todos os grupos. A pressão venosa central, freqüência cardíaca, pressão capilar pulmonar e o índice de resistência pulmonar vascular aumentaram significativamente após a administração de cetamina. O índice cardíaco, o índice de resistência vascular sistêmica e o transporte de oxigênio permaneceram estáveis em todos os grupos. CONCLUSÕES: O etomidato ou a cetamina foram capazes de manter a estabilidade hemodinâmica nos cães que sofreram choque hemorrágico intenso e que foram tratados com NaCl a 0,9 por cento ou NaCl a 7,5 por cento.

Total hepatic ischemia and reperfusion after state controlled hemorrhagic shock, with used of different solutions: effects of neutrophils sequestration in kidney of rats

OBJETIVO: Avaliar e comparar o seqüestro de neutrófilos no rim de rato, como efeito da isquemia e reperfusão hepática total após estado de choque hemorrágico controlado, com uso de diferentes soluções eletrolíticas.MÉTODOS: Utilizou-se 18 ratos Wistar, machos, adultos, divididos em três grupos conforme a solução utilizada para reanimação: Grupo SF: solução fisiológica; Grupo SH: solução hipertônica de NaCl a 7,5% seguido pela solução de ringer com lactato; Grupo RL: solução de ringer com lactato. Todos os animais foram submetidos à sangria controlada até pressão arterial média (PAM) atingir 40 mmHg, permanecendo por 20 minutos. Realizou-se reanimação volêmica até PAM=80 mmHg com a solução conforme o grupo estudado. Em seguida realizou-se uma laparotomia e a manobra de Pringle por 15 minutos. Os animais foram acompanhados até duas horas. Para comparações estatísticas entre as contagens de neutrófilos, no interstício do córtex renal, foram efetuados os testes ANOVA e a análise de covariância, ajustando-se para o tempo de sobrevida. Os parâmetros hemodinâmicos avaliados foram: PAM, freqüência cardíaca, índice cardíaco, índice de resistência vascular sistêmica. As variáveis metabólicas analisadas foram: pH, bicarbonato, reserva de base e lactato, além de eletrólitos. RESULTADOS: Os valores médios de tempo de sobrevida, em minutos, por grupo foram: Grupo SF 79,0±12,0; Grupo RL 97,0±11,0; Grupo SH 67,0±10. Os valores médios da contagem de neutrófilos/campo no córtex renal foram: Grupo SF 0,55±0,68; Grupo RL 1,68±0,53; Grupo SH 1,33±0,43. E quando são ajustados para o tempo de sobrevida encontram-se: Grupo SF 0,55; Grupo RL 1,62; Grupo SH 1,39. Houve diferença estatisticamente significativa, na contagem de neutrófilo entre o Grupo SF com os demais, usando-se ou não o ajuste pelo tempo de sobrevida (p=0,016 e p=0,0128). CONCLUSAO: As duas situações críticas, choque hemorrágico controlado e manobra de Pringle, promoveram seqüestro de neutrófilos no interstício renal do rato, sendo a solução fisiológica com a menor média, diferenciando estatisticamente das demais soluções, neste modelo.

Investigating the relationship between hemodynamic and metabolic parameters in portal triade occlusion following hemorrhagic shock

OBJETIVO: com a utilização de um modelo experimental, determinar se as alterações hemodinâmicas e metabólicas estão "matematicamente" relacionadas em ratos submetidos a estado de choque hemorrágico controlado seguido de isquemia hepática total. MÉTODOS: O coeficiente de correlação de Pearson (valor r) foi utilizado para determinação das fórmulas matemáticas. Diferenças foram consideradas significativas com p<0,05 e -0,50>r>0.50. RESULTADOS: Encontrou-se uma relação diretamente proporcional para o HCO3- quando comparado com pCO2 (r=0,66) e com o déficit de base (r=0,87); e inversamente proporcional quando comparado com o lactato sérico (r=-0,54). O pCO2 esteve diretamente relacionado com a PAM (r=0,51) e inversamente com o pH (r=-0,64). O hematócrito esteve diretamente associado com a freqüência cardíaca (r=0,72) e, também, com o índice cardíaco (r=0,70). O lactato sérico esteve inversamente associado com o déficit de base (r=-0,61). CONCLUSAO: Em ratos submetidos ao estado de choque hemorrágico controlado, por 20 minutos, seguido de manobra de Pringle, por 15 minutos, diversas variáveis hemodinâmicas e metabólicas estão matematicamente associadas.

Metabolic disturbances in shock, and the role of ATP - Mg CL2 and sex steroid

Hemorrhage following accidental injuries is a common cause of death in the industrialized world. Moreover, the impact of elective surgery and solid organ transplantation sometimes results in low flow conditions similar to those seen following hemorrhagic shock. A shortage in O2 availability, or hypoxia, leads to sequential changes in cell metabolism and morphology, including inflammatory responses and the expression of hypoxia-inducible transcription factor-1, which controls the cellular adaptation to hypoxia. These endogenous adaptive responses show that O2 deprivation is not an unforeseen event for cells. The purpose of this review article is to discuss the pathophysiologic principles of shock and the metabolic alterations that cells undergo during low flow conditions. Moreover, the rationale for therapeutic intervention by administering ATP-MgCl2 and sex steroids following shock and trauma will also be discussed