RESUMEN
Down syndrome (DS) is characterized by the trisomy of chromosome 21 and by cognitive deficits that have been related to neuronal morphological alterations in humans, as well as in animal models. The gene encoding for amyloid precursor protein (APP) is present in autosome 21, and its overexpression in DS has been linked to neuronal dysfunction, cognitive deficit, and Alzheimer's disease-like dementia. In particular, the neuronal ability to extend processes and branching is affected. Current evidence suggests that APP could also regulate neurite growth through its role in the actin cytoskeleton, in part by influencing p21-activated kinase (PAK) activity. The latter effect is carried out by an increased abundance of the caspase cleavage-released carboxy-terminal C31 fragment. In this work, using a neuronal cell line named CTb, which derived from the cerebral cortex of a trisomy 16 mouse, an animal model of human DS, we observed an overexpression of APP, elevated caspase activity, augmented cleavage of the C-terminal fragment of APP, and increased PAK1 phosphorylation. Morphometric analyses showed that inhibition of PAK1 activity with FRAX486 increased the average length of the neurites, the number of crossings per Sholl ring, the formation of new processes, and stimulated the loss of processes. Considering our results, we propose that PAK hyperphosphorylation impairs neurite outgrowth and remodeling in the cellular model of DS, and therefore we suggest that PAK1 may be a potential pharmacological target.
Asunto(s)
Síndrome de Down , Ratones , Humanos , Animales , Síndrome de Down/tratamiento farmacológico , Síndrome de Down/genética , Trisomía , Neuronas/metabolismo , Neuritas/metabolismo , Precursor de Proteína beta-Amiloide/genética , Precursor de Proteína beta-Amiloide/metabolismo , Proyección Neuronal , Caspasas/metabolismoAsunto(s)
Betacoronavirus , Infecciones por Coronavirus , Pandemias , Neumonía Viral , COVID-19 , Enfermedad Crítica , Humanos , SARS-CoV-2RESUMEN
In December 2019, a series of patients with severe pneumonia were identified in Wuhan, Hubei province, China, who progressed to severe acute respiratory syndrome and acute respiratory distress syndrome. Subsequently, COVID-19 was attributed to a new betacoronavirus, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Approximately 20% of patients diagnosed as COVID-19 develop severe forms of the disease, including acute hypoxemic respiratory failure, severe acute respiratory syndrome, acute respiratory distress syndrome and acute renal failure and require intensive care. There is no randomized controlled clinical trial addressing potential therapies for patients with confirmed COVID-19 infection at the time of publishing these treatment recommendations. Therefore, these recommendations are based predominantly on the opinion of experts (level C of recommendation).
Asunto(s)
Betacoronavirus , Infecciones por Coronavirus/diagnóstico , Unidades de Cuidados Intensivos/normas , Neumonía Viral/diagnóstico , Respiración Artificial/normas , COVID-19 , Lista de Verificación , Infecciones por Coronavirus/terapia , Enfermedad Crítica , Humanos , Pandemias , Neumonía Viral/terapia , Guías de Práctica Clínica como Asunto , Respiración Artificial/métodos , SARS-CoV-2 , Síndrome Respiratorio Agudo Grave/diagnóstico , Síndrome Respiratorio Agudo Grave/terapiaRESUMEN
ABSTRACT In December 2019, a series of patients with severe pneumonia were identified in Wuhan, Hubei province, China, who progressed to severe acute respiratory syndrome and acute respiratory distress syndrome. Subsequently, COVID-19 was attributed to a new betacoronavirus, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Approximately 20% of patients diagnosed as COVID-19 develop severe forms of the disease, including acute hypoxemic respiratory failure, severe acute respiratory syndrome, acute respiratory distress syndrome and acute renal failure and require intensive care. There is no randomized controlled clinical trial addressing potential therapies for patients with confirmed COVID-19 infection at the time of publishing these treatment recommendations. Therefore, these recommendations are based predominantly on the opinion of experts (level C of recommendation).
RESUMO Em dezembro de 2019, uma série de pacientes com pneumonia grave foi identificada em Wuhan, província de Hubei, na China. Esses pacientes evoluíram para síndrome respiratória aguda grave e síndrome do desconforto respiratório agudo. Posteriormente, a COVID-19 foi atribuída a um novo betacoronavírus, o coronavírus da síndrome respiratória aguda grave 2 (SARS-CoV-2). Cerca de 20% dos pacientes com diagnóstico de COVID-19 desenvolvem formas graves da doença, incluindo insuficiência respiratória aguda hipoxêmica, síndrome respiratória aguda grave, síndrome do desconforto respiratório agudo e insuficiência renal aguda e requerem admissão em unidade de terapia intensiva. Não há nenhum ensaio clínico randomizado controlado que avalie potenciais tratamentos para pacientes com infecção confirmada pela COVID-19 no momento da publicação destas recomendações de tratamento. Dessa forma, essas recomendações são baseadas predominantemente na opinião de especialistas (grau de recomendação de nível C).
Asunto(s)
Humanos , Neumonía Viral/diagnóstico , Respiración Artificial/normas , Infecciones por Coronavirus/diagnóstico , Betacoronavirus , Unidades de Cuidados Intensivos/normas , Neumonía Viral/terapia , Respiración Artificial/métodos , Enfermedad Crítica , Guías de Práctica Clínica como Asunto , Infecciones por Coronavirus/terapia , Síndrome Respiratorio Agudo Grave/diagnóstico , Síndrome Respiratorio Agudo Grave/terapia , Lista de Verificación , Pandemias , SARS-CoV-2 , COVID-19Asunto(s)
Humanos , Neumonía Viral , Infecciones por Coronavirus , Pandemias , Betacoronavirus , Enfermedad Crítica , SARS-CoV-2 , COVID-19RESUMEN
BACKGROUND: Several studies have shown that the distribution of cardiac output to the intra-abdominal organs may vary during low-flow states. In this study, we developed an experimental model to selectively reduce the abdominal aortic blood flow in order to assess the initial impact of selective hepatosplanchnic hypoperfusion on regional blood flow redistribution. METHODS: Eight anesthetized and mechanically ventilated mongrel dogs were subjected to aortic blood flow reduction with an occluder in a stepwise manner by 50% and 100% for 45 min. After the ischemic period, the occluder was released, and animals were observed for an additional 45 min. Systemic hemodynamics were evaluated through a Swan-Ganz and arterial catheters, and gastrointestinal tract perfusion was evaluated by portal vein and hepatic arterial blood flows measurements (ultrasonic flowprobe). Intestinal O2-derived variables, intestinal mucosal (tonometric)-arterial and tonometric-(end-tidal-carbon-dioxide) gradients (Dt-apCO2 and Dt-EtpCO2) were also calculated. RESULTS: No significant changes in systemic and regional oxygen consumption were observed during the 50% reduction of aortic blood flow. On the other hand, both microregional pCO2 gradients (Dt-apCO2 e Dt-EtpCO2) showed a significant increase during this period. Aortic occlusion was associated with a marked reduction of systemic and regional oxygen delivery and consumption. During the reperfusion, no significant improvement in the tonometry-based pCO2 gradients was observed, in spite of the partial reestablishment of blood flow to the hepatosplanchnic territory. CONCLUSION: During selective intra-abdominal low-flow, a proportional reduction in the splanchnic and hepatic blood flows occurs. A selective reduction of approximately 50% in splanchnic oxygen delivery was not associated with significant changes in macroregional markers of hypoperfusion. In this situation, tonometry-based pCO2 gradients can be used for the assessment of hepatosplanchnic perfusion and histologic changes.
Asunto(s)
Aorta Abdominal/fisiología , Hemodinámica/fisiología , Consumo de Oxígeno/fisiología , Choque/metabolismo , Choque/fisiopatología , Animales , Presión Sanguínea/fisiología , Tampones (Química) , Gasto Cardíaco/fisiología , Perros , Hígado/irrigación sanguínea , Hígado/metabolismo , Hígado/patología , Circulación Hepática/fisiología , Masculino , Manometría , Daño por Reperfusión/metabolismo , Daño por Reperfusión/patología , Daño por Reperfusión/fisiopatología , Choque/patología , Bazo/irrigación sanguínea , Bazo/metabolismo , Bazo/patologíaRESUMEN
BACKGROUND: Hydroxyethylstarch (HES) is a synthetic polymer of glucose that has been suggested for therapeutic use in long-term plasma expansion. The aim of this study was to test the hypothesis that the infusion of a small volume of HES may provide benefits in systemic and regional hemodynamics and metabolism in a brain-dead canine model compared with large volume crystalloid resuscitation. METHODS: Fourteen mongrel dogs were subjected to a brain-death protocol by consecutive insufflations of a balloon catheter in the epidural space. One hour after induction of brain-death, the animals were randomly assigned to two groups: NS (0.9% NaCl, 33 mL/kg), and HES (6%HES 450/0.7, 17 mL/Kg). Systemic and regional hemodynamics were evaluated using Swan-Ganz, ultrasonic flowprobes, and arterial catheters. Serial blood samples were collected for blood gas, electrolyte, and serum chemistry analysis. Systemic, hepatic, and splanchnic O(2)-derived variables were also calculated. RESULTS: Epidural balloon insufflations induced a significant increase in mean arterial pressure, cardiac output (MAP and CO, respectively), regional blood flow, and systemic vascular resistance. Following the hyperdynamic phase, severe hypotension with normalization of systemic and regional blood flow was observed. Fluid resuscitation induced a prompt increase in MAP, CO, and portal vein blood flow, and a significant reduction in systemic and pulmonary vascular resistance. There were no differences between groups in metabolic indices, liver function tests (LFTs), or renal function tests. HES was more effective than NS in restoring cardiac performance in the first 2h after fluid resuscitation (P < 0.05). Both tested solutions partially and temporarily restored systemic and regional oxygen delivery. CONCLUSION: Small volumes of 6% HES 450/0.7 improved cardiovascular performance and provided the same regional hemodynamic and metabolic benefits of large volumes of isotonic crystalloid solutions.
Asunto(s)
Muerte Encefálica/metabolismo , Muerte Encefálica/fisiopatología , Hemodinámica/efectos de los fármacos , Derivados de Hidroxietil Almidón/farmacología , Sustitutos del Plasma/farmacología , Resucitación/métodos , Alanina Transaminasa/metabolismo , Animales , Presión Sanguínea/efectos de los fármacos , Presión Sanguínea/fisiología , Gasto Cardíaco/efectos de los fármacos , Gasto Cardíaco/fisiología , Creatina Quinasa/metabolismo , Perros , Glucosa/metabolismo , Masculino , Modelos Animales , Flujo Sanguíneo Regional/efectos de los fármacos , Flujo Sanguíneo Regional/fisiología , Cloruro de Sodio/farmacología , Resistencia Vascular/efectos de los fármacos , Resistencia Vascular/fisiologíaRESUMEN
BACKGROUND: Acute mesenteric ischemia is a potentially fatal vascular emergency with mortality rates ranging between 60% and 80%. Several studies have extensively examined the hemodynamic and metabolic effects of superior mesenteric artery occlusion. On the other hand, the cardiocirculatory derangement and the tissue damage induced by intestinal outflow obstruction have not been investigated systematically. For these reasons we decided to assess the initial impact of venous mesenteric occlusion on intestinal blood flow distribution, and correlate these findings with other systemic and regional perfusion markers. METHODS: Fourteen mongrel dogs were subjected to 45 min of superior mesenteric artery (SMAO) or vein occlusion (SMVO), and observed for 120 min after reperfusion. Systemic hemodynamics were evaluated using Swan-Ganz and arterial catheters. Regional blood flow (ultrasonic flow probes), intestinal O(2)-derived variables, and mesenteric-arterial and tonometric-arterial pCO(2) gradients (D(mv-a)pCO(2) and D(t-a)pCO(2)) were also calculated. RESULTS: SMVO was associated with hypotension and low cardiac output. A significant increase in the regional pCO(2) gradients was also observed in both groups during the ischemic period. After reperfusion, a progressive reduction in D(mv-a)pCO(2) occurred in the SMVO group; however, no improvement in D(t-a)pCO(2) was observed. The histopathologic injury scores were 2.7 +/- 0.5 and 4.8 +/- 0.2 for SMAO and SMVO, respectively. CONCLUSIONS: SMV occlusion promoted early and significant hemodynamic and metabolic derangement at systemic and regional levels. Additionally, systemic pCO(2) gradient is not a reliable parameter to evaluate the local intestinal oxygenation. Finally, the D(t-a)pCO(2) correlates with histologic changes during intestinal congestion or ischemia. However, minor histologic changes cannot be detected using this methodology.
Asunto(s)
Hiperemia/fisiopatología , Mucosa Intestinal/fisiopatología , Isquemia/fisiopatología , Mesenterio/irrigación sanguínea , Circulación Esplácnica , Animales , Perros , Hemodinámica , Hiperemia/metabolismo , Hiperemia/patología , Mucosa Intestinal/irrigación sanguínea , Mucosa Intestinal/patología , Isquemia/metabolismo , Isquemia/patología , Masculino , Oxígeno/metabolismo , Flujo Sanguíneo RegionalRESUMEN
BACKGROUND: Splanchnic perfusion is prone to early injury and persists despite normalization of global hemodynamic variables in sepsis. Volume replacement guided by oxygen derived variables has been recommended in the management of septic patients. Our hypothesis was that a hypertonic isoncotic solution would improve the benefits of crystalloids replacement guided by mixed venous oxygen saturation. METHODS: Seventeen anesthetized and mechanically ventilated mongrel dogs received an intravenous infusion of live E. coli in 30 minutes. They were then randomized into three groups: control group (n = 3) bacterial infusion without treatment; normal saline (n = 7), initial fluid replacement with 32 mL/kg of normal saline during 20 minutes; hypertonic solution (n = 7), initial fluid replacement with 4 mL/kg of hypertonic solution during 5 minutes. After 30 and 60 minutes, additional boluses of normal saline were administered when mixed venous oxygen saturation remained below 70%. Mean arterial pressure, cardiac output; regional blood flows, systemic and regional oxygen-derived variables, and lactate levels were assessed. Animals were observed for 90 minutes and then killed. Hystopathological analysis including apoptosis detection using terminal deoxynucleotidil transferase mediated dUTP-biotin nick end labeling was performed. RESULTS: A hypodynamic septic shock was observed after bacterial infusion. Both the fluid-treated groups presented similar transient benefits in systemic and regional variables. A greater degree of gut epithelial cells apoptosis was observed in normal saline-treated animals. CONCLUSIONS: Although normalization of mixed venous oxygen saturation was not associated with restoration of markers of splanchnic or other systemic perfusion variables, the initial fluid savings with hypertonic saline and its latter effect on gut apoptosis may be of interest in sepsis management.
Asunto(s)
Fluidoterapia/métodos , Oxígeno/sangre , Solución Salina Hipertónica/administración & dosificación , Choque Séptico/terapia , Animales , Análisis de los Gases de la Sangre/métodos , Modelos Animales de Enfermedad , Perros , Etiquetado Corte-Fin in Situ , Distribución Aleatoria , Choque Séptico/fisiopatologíaRESUMEN
PURPOSE: Multivisceral transplantation (MVTx) has been accepted as standard therapeutic modality for patients with short-bowel syndrome associated with irreversible liver failure. Even nowadays, experimental models of MVTx grounds high incidence of intraoperative or early recipient mortality. Despite the known deleterious effects of hepatosplanchnic exenteration the impact of this procedure on systemic hemodynamics and metabolism remains to be determined. METHODS: Nine dogs (20.1+/-0.5 kg) were subjected to an en bloc resection of all abdominal organs including, stomach, duodenum, pancreas, liver, spleen, small bowel, and colon. A woven double velour vascular graft was interposed between the suprahepatic and infrahepatic vena cava. Systemic hemodynamic were evaluated through a Swan-Ganz catheter, ultrasonic flowprobes, and arterial lines. Systemic O2-derived variables, glucose, and lactate metabolism were analyzed throughout the experiment. RESULTS: Complete abdominal exenteration was associated with significant reduction in cardiac output, and mean arterial pressure (57% and 14%, respectively). Two hours after reperfusion a significant reduction in arterial pH and glucose were also observed. Oxygen consumption remained unaltered during the first two hours of the experiment, with a significant increase of lactate levels (1.4+/-0.3 vs. 7.6+/-0.4, p<0.05). Three animals died before the 3 hours of reperfusion were completed. Total abdominal exenteration for MVTx in dogs is associated with early major hemodynamics, and metabolic changes. CONCLUSION: The deleterious hemodynamic alterations observed are probably related with the association of severe acidosis, hyperlactemia, hypoglycemia, and reduction of total circulating blood volume. Close hemodynamic and metabolic monitoring should be provided during experimental MVTx in order to promote an increase in successful rates of this complex and challenging procedure.
Asunto(s)
Anestesia/métodos , Hemodinámica/fisiología , Trasplante de Órganos/fisiología , Traumatismos Abdominales/complicaciones , Traumatismos Abdominales/metabolismo , Traumatismos Abdominales/cirugía , Animales , Modelos Animales de Enfermedad , Perros , Masculino , Flujo Sanguíneo Regional/fisiologíaRESUMEN
PURPOSE: Multivisceral transplantation (MVTx) has been accepted as standard therapeutic modality for patients with short-bowel syndrome associated with irreversible liver failure. Even nowadays, experimental models of MVTx grounds high incidence of intraoperative or early recipient mortality. Despite the known deleterious effects of hepatosplanchnic exenteration the impact of this procedure on systemic hemodynamics and metabolism remains to be determined. METHODS: Nine dogs (20.1±0.5 kg) were subjected to an en bloc resection of all abdominal organs including, stomach, duodenum, pancreas, liver, spleen, small bowel, and colon. A woven double velour vascular graft was interposed between the suprahepatic and infrahepatic vena cava. Systemic hemodynamic were evaluated through a Swan-Ganz catheter, ultrasonic flowprobes, and arterial lines. Systemic O2-derived variables, glucose, and lactate metabolism were analyzed throughout the experiment. RESULTS: Complete abdominal exenteration was associated with significant reduction in cardiac output, and mean arterial pressure (57% and 14%, respectively). Two hours after reperfusion a significant reduction in arterial pH and glucose were also observed. Oxygen consumption remained unaltered during the first two hours of the experiment, with a significant increase of lactate levels (1.4±0.3 vs. 7.6±0.4, p<0.05). Three animals died before the 3 hours of reperfusion were completed. Total abdominal exenteration for MVTx in dogs is associated with early major hemodynamics, and metabolic changes. CONCLUSION: The deleterious hemodynamic alterations observed are probably related with the association of severe acidosis, hyperlactemia, hypoglycemia, and reduction of total circulating blood volume. Close hemodynamic and metabolic monitoring should be provided during experimental MVTx in order to promote an increase in successful rates of this complex and challenging procedure.
OBJETIVO: O transplante multivisceral (MVTx) é preconizado como tratamento de escolha em pacientes com síndrome do intestine curto associado com falência hepática irreverssível. Modelos experimentais de MVTx apresentam altas taxas de mortalidade intra-operatória e nas primeiras horas apos a reperfusão. Apesar dos deletérios efeitos hemodinâmicos da exenteração abdominal, o impacto deste procedimento na perfusão e no metabolismo sistêmico ainda esta por ser determinado. MÉTODOS: Nove cães (20.1±0.5 kg) foram submetidos a ressecção em bloco de todos os orgãos abdominais incluindo, estômago, duodeno, pancreas, fígado, baço, intestino delgado, e colon. Uma prótese vascular foi interposta entre a veia cava infra e supra-hepática. Efeitos hemodinâmicos foram avaliados por meio de um cateter de Swan-Ganz catheter e Doppler ultrassônico. As variáveis dependentes de oxigênio, e o metabolismo da glicose e lactato foram avaliados durante todo o experimento. RESULTADOS: A evisceração abdominal esteve associada a uma redução significativa do débito cardiaco e da pressão arterial média (57% and 14%, respectivamente). Duas horas após a reconstrução vascular da veia cava inferior observou-se uma redução significativa do pH e da glicose arterial. O consumo de oxigênio se manteve inalterado nas primeiras duas horas do experimento, com um significativo aumento dos níveis séricos de lactato (1.4±0.3 vs. 7.6±0.4, p<0.05). Três animais morreram antes de 180 minutos após a reperfusão. CONCLUSÃO: A evisceração abdominal total esteve associada com graves repercussões hemodinâmicas e metabólicas sistêmicas. Estas graves alterações hemodinâmicas estam associadas, provavelmente, a combinação de vários fatores incluindo: acidose metabólica, hiperlactemia, hipoglicemia e redução do volume de sangue circulante. A cuidadosa monitorização hemodinâmica e metabólica deve ser realizada durante o MVTx experimental com a finalidade de promover um aumento...
Asunto(s)
Animales , Perros , Masculino , Anestesia/métodos , Hemodinámica/fisiología , Trasplante de Órganos/fisiología , Traumatismos Abdominales/complicaciones , Traumatismos Abdominales/metabolismo , Traumatismos Abdominales/cirugía , Modelos Animales de Enfermedad , Flujo Sanguíneo Regional/fisiologíaRESUMEN
PURPOSE: Multivisceral transplantation (MVTx) has been accepted as standard therapeutic modality for patients with short-bowel syndrome associated with irreversible liver failure. Even nowadays, experimental models of MVTx grounds high incidence of intraoperative or early recipient mortality. Despite the known deleterious effects of hepatosplanchnic exenteration the impact of this procedure on systemic hemodynamics and metabolism remains to be determined. METHODS: Nine dogs (20.1±0.5 kg) were subjected to an en bloc resection of all abdominal organs including, stomach, duodenum, pancreas, liver, spleen, small bowel, and colon. A woven double velour vascular graft was interposed between the suprahepatic and infrahepatic vena cava. Systemic hemodynamic were evaluated through a Swan-Ganz catheter, ultrasonic flowprobes, and arterial lines. Systemic O2-derived variables, glucose, and lactate metabolism were analyzed throughout the experiment. RESULTS: Complete abdominal exenteration was associated with significant reduction in cardiac output, and mean arterial pressure (57% and 14%, respectively). Two hours after reperfusion a significant reduction in arterial pH and glucose were also observed. Oxygen consumption remained unaltered during the first two hours of the experiment, with a significant increase of lactate levels (1.4±0.3 vs. 7.6±0.4, p<0.05). Three animals died before the 3 hours of reperfusion were completed. Total abdominal exenteration for MVTx in dogs is associated with early major hemodynamics, and metabolic changes. CONCLUSION: The deleterious hemodynamic alterations observed are probably related with the association of severe acidosis, hyperlactemia, hypoglycemia, and reduction of total circulating blood volume. Close hemodynamic and metabolic monitoring should be provided during experimental MVTx in order to promote an increase in successful rates of this complex and challenging procedure.(AU)
OBJETIVO: O transplante multivisceral (MVTx) é preconizado como tratamento de escolha em pacientes com síndrome do intestine curto associado com falência hepática irreverssível. Modelos experimentais de MVTx apresentam altas taxas de mortalidade intra-operatória e nas primeiras horas apos a reperfusão. Apesar dos deletérios efeitos hemodinâmicos da exenteração abdominal, o impacto deste procedimento na perfusão e no metabolismo sistêmico ainda esta por ser determinado. MÉTODOS: Nove cães (20.1±0.5 kg) foram submetidos a ressecção em bloco de todos os orgãos abdominais incluindo, estômago, duodeno, pancreas, fígado, baço, intestino delgado, e colon. Uma prótese vascular foi interposta entre a veia cava infra e supra-hepática. Efeitos hemodinâmicos foram avaliados por meio de um cateter de Swan-Ganz catheter e Doppler ultrassônico. As variáveis dependentes de oxigênio, e o metabolismo da glicose e lactato foram avaliados durante todo o experimento. RESULTADOS: A evisceração abdominal esteve associada a uma redução significativa do débito cardiaco e da pressão arterial média (57% and 14%, respectivamente). Duas horas após a reconstrução vascular da veia cava inferior observou-se uma redução significativa do pH e da glicose arterial. O consumo de oxigênio se manteve inalterado nas primeiras duas horas do experimento, com um significativo aumento dos níveis séricos de lactato (1.4±0.3 vs. 7.6±0.4, p<0.05). Três animais morreram antes de 180 minutos após a reperfusão. CONCLUSÃO: A evisceração abdominal total esteve associada com graves repercussões hemodinâmicas e metabólicas sistêmicas. Estas graves alterações hemodinâmicas estam associadas, provavelmente, a combinação de vários fatores incluindo: acidose metabólica, hiperlactemia, hipoglicemia e redução do volume de sangue circulante. A cuidadosa monitorização hemodinâmica e metabólica deve ser realizada durante o MVTx experimental com a finalidade de promover um aumento...(AU)
Asunto(s)
Animales , Hemodinámica , Flujo Sanguíneo Regional , Síndrome del Intestino Corto/fisiopatología , PerrosRESUMEN
BACKGROUND: Organs from the so-called marginal donors have been used with a significant higher risk of primary non function than organs retrieved from the optimal donors. We investigated the early metabolic changes and blood flow redistribution in splanchnic territory in an experimental model that mimics marginal brain-dead (BD) donor. MATERIAL/METHODS: Ten dogs (21.3+/-0.9 kg), were subjected to a brain death protocol induced by subdural balloon inflation and observed for 30 min thereafter without any additional interventions. Mean arterial and intracranial pressures, heart rate, cardiac output (CO), portal vein and hepatic artery blood flows (PVBF and HABF, ultrasonic flowprobe), and O(2)-derived variables were evaluated. RESULTS: An increase in arterial pressure, CO, PVBF and HABF was observed after BD induction. At the end, an intense hypotension with normalization in CO (3.0+/-0.2 vs. 2.8+/-2.8 L/min) and PVBF (687+/-114 vs. 623+/-130 ml/min) was observed, whereas HABF (277+/-33 vs. 134+/-28 ml/min, p<0.005) remained lower than baseline values. CONCLUSIONS: Despite severe hypotension induced by sudden increase of intracranial pressure, the systemic and splanchnic blood flows were partially preserved without signs of severe hypoperfusion (i.e. hyperlactatemia). Additionally, the HABF was mostly negatively affected in this model of marginal BD donor. Our data suggest that not only the cardiac output, but the intrinsic hepatic microcirculatory mechanism plays a role in the hepatic blood flow control after BD.
Asunto(s)
Muerte Encefálica/fisiopatología , Modelos Animales de Enfermedad , Oxígeno/sangre , Circulación Esplácnica/fisiología , Animales , Muerte Encefálica/metabolismo , Gasto Cardíaco/fisiología , Perros , Hemodinámica , Circulación Hepática/fisiología , Microcirculación , Vena Porta/fisiopatología , Flujo Sanguíneo RegionalRESUMEN
Although cardiovascular effects of cocaine have been well studied, little is known about its effects on splanchnic perfusion. We studied systemic and regional hemodynamic effects of acute cocaine intoxication in dogs under volatile anesthesia. Mechanically ventilated beagle dogs, randomized at 1.5% halothane (n = 7) or 2.25% sevoflurane (n = 7) anesthesia, received an intravenous bolus of cocaine (12 mg/kg over 5 min) followed by 0.22 mg/kg/min infusion over 30 min. They were observed for 60 min thereafter. Cardiac index (CI), heart rate (HR), mean arterial pressure (MAP), portal blood flow (PBF), gastric PCO(2) (gas tonometry), blood gases, and lactate and cocaine levels were assessed. Cocaine bolus promoted significant reductions in CI (~50%), HR (~20%), MAP (~20%), and PBF (~50%), accompanied by increase in systemic and splanchnic oxygen extractions and in gastric mucosal-arterial PCO(2) gradient. Those changes were maintained during cocaine infusion and returned to baseline values parallel to plasmatic cocaine clearance. Unlike other shock states, regional parameters, including gastric mucosal-arterial PCO(2) gradient, were restored before systemic variables. A possible local vasodilatory effect of volatile agents could play a role in this phenomenon. Cocaine infusion in anesthetized animals promoted marked systemic and regional hemodynamic derangement, which was rapidly reversible with decay of cocaine plasmatic concentration.
Asunto(s)
Cocaína/farmacología , Circulación Esplácnica/efectos de los fármacos , Anestesia , Animales , Presión Sanguínea/efectos de los fármacos , Gasto Cardíaco/efectos de los fármacos , Cocaína/sangre , Perros , Halotano/farmacología , Frecuencia Cardíaca/efectos de los fármacos , MasculinoAsunto(s)
Humanos , Dermatosis del Cuero Cabelludo/parasitología , Dermatosis del Cuero Cabelludo/tratamiento farmacológico , Dermatosis del Cuero Cabelludo/terapia , Infestaciones por Piojos/tratamiento farmacológico , Hexaclorociclohexano , Malatión , Aceites Volátiles , Permetrina , Aceites de Plantas , Pediculus/genéticaRESUMEN
Pulse pressure (DeltaPp) and systolic pressure (DeltaPs) variations have been recommended as predictors of fluid responsiveness in critically ill patients. We hypothesized that changes in DeltaPp and DeltaPs parallel alterations in stroke volume (SV) and cardiac output (CO) during hemorrhage, shock, and resuscitation. In anesthetized and mechanically ventilated mongrel dogs, a graded hemorrhage (20 mL/min) was induced to a target mean arterial pressure (MAP) of 40 mm Hg, which was maintained for additional 30 min. Total shed-blood volume was then retransfused at a 40 mL/min rate. CO, SV, right atrial pressure (RAP), pulmonary artery occlusion pressure (PAOP), and continuous mixed venous oxygen saturation (SvO(2)) were assessed. Both DeltaPp and DeltaPs were calculated from direct arterial pressure waveform. Removal of about 9% of estimated blood volume promoted a reduction in SV (14.8 +/- 2.2 to 10.6 +/- 1.3 mL, P < 0.05). At approximately 18% blood volume removal, significant changes in CO (2.4 +/- 0.2 to 1.5 +/- 0.2 mL/min, P < 0.05), DeltaPp (12.6 +/- 1.4 to 15.8 +/- 2.0%, P < 0.05), and SvO(2) (82 +/- 1.4 to 73 +/- 1.7%, P < 0.05) were observed. Alterations in MAP, RAP, PAOP, and DeltaPs could be detected only after each animal had lost over 36% of estimated initial blood volume. There was correlation between blood volume loss and SV, CO, and SvO(2), as well as between blood loss and MAP, DeltaPp, and DeltaPs. Blood volume loss showed no correlation with cardiac filling pressures. DeltaPp is a useful, early marker of SV and CO for the assessment of cardiac preload changes in hemorrhagic shock, while cardiac filling pressures are not.
Asunto(s)
Biomarcadores , Presión Sanguínea/fisiología , Gasto Cardíaco/fisiología , Choque Hemorrágico/fisiopatología , Animales , Transfusión Sanguínea , Volumen Sanguíneo , Modelos Animales de Enfermedad , Perros , Hipovolemia/fisiopatología , Hipovolemia/terapia , Masculino , Respiración Artificial , Choque Hemorrágico/terapia , Volumen Sistólico/fisiologíaRESUMEN
PURPOSE: To evaluate the effects of SSH resuscitation on systemic and splanchnic hemodynamic variables in an experimental model of controlled hemorrhagic shock. METHODS: Ten mongrel dogs were bled (20 ml/min) to a target mean arterial pressure (MAP) of 40+/-5 mmHg. After 30 minutes of shock, animals received SSH infused in 5-minute and they were observed for 60 minutes thereafter. Systemic hemodynamics were evaluated through a Swan-Ganz and arterial catheters while gastrointestinal tract perfusion by a catheter inside the portal vein, an ultrasonic flowprobe around portal vein blood flow (PVBF) and a gastric tonometer. Splanchnic oxygen delivery and consumption, intramucosal pH and veno-arterial, portal-arterial and mucosal-arterial pCO2-gradients (D(ap-a)pCO2, D(vp-a)pCO2 e D(t-a)pCO2, respectively) were assessed. RESULTS: Hemorrhage (29.8+/-2.4 ml/Kg) induced significant decreases in MAP (125+/-6 to 42+/-1 mmHg), in CO (1.9+/-0.2 to 0.6+/-0.1 L/min), and PVBF (504+/-73 to 126+/-12 ml/min) while significant increases were detected in D(ap-a)pCO2 (5.3+/-0.8 to 19.9+/-1.6 mmHg) D(vp-a)pCO2 (5.4+/-1.4 to 22.6+/-2.1 mmHg) and D(t-a)pCO2 (6.1+/-1.1 to 43.8+/-7.5 mmHg). SSH infusion promoted only partial benefits in systemic and splanchnic blood flows. Reduced pCO2 gradients but fewer effects in D(t-a)pCO2 were observed. CONCLUSION: The SSH infusion promoted partial systemic and splanchnic hemodynamic benefits. Those benefits were especially poor at the splanchnic microcirculation, as evaluated by D(t-a)pCO2. In addition, systemic and regional oxygen-derived variables do not reflect the regional microcirculation disturbances. Gastrointestinal tonometry clearly represents a useful tool for monitoring splanchnic perfusion in patients in hemodynamic shock.
Asunto(s)
Reperfusión/métodos , Resucitación/métodos , Solución Salina Hipertónica/administración & dosificación , Choque Hemorrágico/terapia , Circulación Esplácnica/efectos de los fármacos , Animales , Perros , Concentración de Iones de Hidrógeno , Mucosa Intestinal/irrigación sanguíneaRESUMEN
INTRODUCTION: We conducted the present study to examine the effects of hypertonic saline solution (7.5%) on cardiovascular function and splanchnic perfusion in experimental sepsis. METHODS: Anesthetized and mechanically ventilated mongrel dogs received an intravenous infusion of live Escherichia coli over 30 minutes. After 30 minutes, they were randomized to receive lactated Ringer's solution 32 ml/kg (LR; n = 7) over 30 minutes or 7.5% hypertonic saline solution 4 ml/kg (HS; n = 8) over 5 minutes. They were observed without additional interventions for 120 minutes. Cardiac output (CO), mean arterial pressure (MAP), portal and renal blood flow (PBF and RBF, respectively), gastric partial pressure of CO2 (pCO2; gas tonometry), blood gases and lactate levels were assessed. RESULTS: E. coli infusion promoted significant reductions in CO, MAP, PBF and RBF (approximately 45%, 12%, 45% and 25%, respectively) accompanied by an increase in lactate levels and systemic and mesenteric oxygen extraction (sO2ER and mO2ER). Widening of venous-arterial (approximately 15 mmHg), portal-arterial (approximately 18 mmHg) and gastric mucosal-arterial (approximately 55 mmHg) pCO2 gradients were also observed. LR and HS infusion transiently improved systemic and regional blood flow. However, HS infusion was associated with a significant and sustained reduction of systemic (18 +/- 2.6 versus 38 +/- 5.9%) and mesenteric oxygen extraction (18.5 +/- 1.9 versus 36.5 +/- 5.4%), without worsening other perfusional markers. CONCLUSION: A large volume of LR or a small volume of HS promoted similar transient hemodynamic benefits in this sepsis model. However, a single bolus of HS did promote sustained reduction of systemic and mesenteric oxygen extraction, suggesting that hypertonic saline solution could be used as a salutary intervention during fluid resuscitation in septic patients.
Asunto(s)
Fluidoterapia/métodos , Solución Salina Hipertónica/administración & dosificación , Sepsis/terapia , Animales , Análisis de los Gases de la Sangre/métodos , Modelos Animales de Enfermedad , Perros , Masculino , Sepsis/fisiopatologíaRESUMEN
OBJETIVO: Avaliar os efeitos hemodinâmicos sistêmicos e esplâncnico da expansão volêmica inicial com SSH em modelo de choque hemorrágico controlado. MÉTODOS: Dez cães foram submetidos a sangramento controlado (20 ml/min) até uma pressão arterial média de 40±5 mmHg (PAM). Após 30 minutos de choque, receberam 4 ml/Kg de SSH em 5 minutos e posteriormente observados sem intervenções adicionais durante 60 minutos. As variáveis hemodinâmicas sistêmicas foram obtidas de um cateter arterial e de um cateter de Swan-Ganz, enquanto as regionais através da cateterização da veia porta, fluxômetro ultrassônico na veia porta e um tonômetro na cavidade. A oferta, taxa de extração e consumo esplâncnico de oxigênio, pH intramucoso e os gradientes veno-arterial, porta-arterial e mucosa-arterial da pCO2 (Dap-a pCO2, Dvp-a pCO2 e Dt-a pCO2, respectivamente), foram calculados. RESULTADOS: A hemorragia (29,8±2,4 ml/Kg) reduziu a pressão arterial média (125±6 para 42±1 mmHg), o DC (1,9±0,2 para 0,6±0,1 L/min) e o fluxo porta (504±73 para 126±12 ml/min), enquanto elevou o Dap-a pCO2 (5,3±0,8 para 19,9±1,6 mmHg), Dvp-a pCO2 (5,4±1,4 para 22,6±2,1 mmHg) e o Dt-a pCO2 (6,1±1,1 para 43,8±7,5 mmHg). A infusão de SSH resultou em recuperação parcial dos fluxos sistêmico e porta. Atenuou os gradientes de CO2 com menor impacto sobre o Dt-a pCO2. CONCLUSÃO: A SSH promoveu benefícios parciais na perfusão sistêmica e esplâncnica, os quais foram especialmente limitados na microcirculação regional, como demonstrado pelo Dt-a pCO2. Além disso, as variáveis sistêmicas e regionais dependentes de oxigênio, não refletem a adequação da perfusão da mucosa gástrica, enfatizando a importância da monitorização deste território - pela tonometria - durante os estados de choque.
Asunto(s)
Animales , Perros , Perfusión/métodos , Resucitación/métodos , Solución Salina Hipertónica/administración & dosificación , Choque Hemorrágico/terapia , Circulación Esplácnica/efectos de los fármacos , Concentración de Iones de Hidrógeno , Mucosa Intestinal/irrigación sanguíneaRESUMEN
OBJETIVO: Avaliar os efeitos hemodinâmicos sistêmicos e esplâncnico da expansão volêmica inicial com SSH em modelo de choque hemorrágico controlado. MÉTODOS: Dez cães foram submetidos a sangramento controlado (20 ml/min) até uma pressão arterial média de 40±5 mmHg (PAM). Após 30 minutos de choque, receberam 4 ml/Kg de SSH em 5 minutos e posteriormente observados sem intervenções adicionais durante 60 minutos. As variáveis hemodinâmicas sistêmicas foram obtidas de um cateter arterial e de um cateter de Swan-Ganz, enquanto as regionais através da cateterização da veia porta, fluxômetro ultrassônico na veia porta e um tonômetro na cavidade. A oferta, taxa de extração e consumo esplâncnico de oxigênio, pH intramucoso e os gradientes veno-arterial, porta-arterial e mucosa-arterial da pCO2 (Dap-a pCO2, Dvp-a pCO2 e Dt-a pCO2, respectivamente), foram calculados. RESULTADOS: A hemorragia (29,8±2,4 ml/Kg) reduziu a pressão arterial média (125±6 para 42±1 mmHg), o DC (1,9±0,2 para 0,6±0,1 L/min) e o fluxo porta (504±73 para 126±12 ml/min), enquanto elevou o Dap-a pCO2 (5,3±0,8 para 19,9±1,6 mmHg), Dvp-a pCO2 (5,4±1,4 para 22,6±2,1 mmHg) e o Dt-a pCO2 (6,1±1,1 para 43,8±7,5 mmHg). A infusão de SSH resultou em recuperação parcial dos fluxos sistêmico e porta. Atenuou os gradientes de CO2 com menor impacto sobre o Dt-a pCO2. CONCLUSÃO: A SSH promoveu benefícios parciais na perfusão sistêmica e esplâncnica, os quais foram especialmente limitados na microcirculação regional, como demonstrado pelo Dt-a pCO2. Além disso, as variáveis sistêmicas e regionais dependentes de oxigênio, não refletem a adequação da perfusão da mucosa gástrica, enfatizando a importância da monitorização deste território - pela tonometria - durante os estados de choque. (AU)
PURPOSE: To evaluate the effects of SSH resuscitation on systemic and splanchnic hemodynamic variables in an experimental model of controlled hemorrhagic shock.METHODS: Ten mongrel dogs were bled (20 ml/min) to a target mean arterial pressure (MAP) of 40±5 mmHg. After 30 minutes of shock, animals received SSH infused in 5-minute and they were observed for 60 minutes thereafter. Systemic hemodynamics were evaluated through a Swan-Ganz and arterial catheters while gastrointestinal tract perfusion by a catheter inside the portal vein, an ultrasonic flowprobe around portal vein blood flow (PVBF) and a gastric tonometer. Splanchnic oxygen delivery and consumption, intramucosal pH and veno-arterial, portal-arterial and mucosal-arterial pCO2-gradients (Dap-apCO2, Dvp-apCO2 e Dt-apCO2, respectively) were assessed.RESULTS: Hemorrhage (29.8±2.4ml/Kg) induced significant decreases in MAP (125±6 to 42±1 mmHg), in CO (1.9±0.2 to 0.6±0.1 L/min), and PVBF (504±73 to 126±12 ml/min) while significant increases were detected in Dap-apCO2 (5.3±0.8 to 19.9±1.6 mmHg) Dvp-apCO2 (5.4±1.4 to 22.6±2.1 mmHg) and Dt-apCO2 (6.1±1.1 to 43.8±7.5 mmHg). SSH infusion promoted only partial benefits in systemic and splanchnic blood flows. Reduced pCO2 gradients but fewer effects in Dt-apCO2 were observed.CONCLUSION: The SSH infusion promoted partial systemic and splanchnic hemodynamic benefits. Those benefits were especially poor at the splanchnic microcirculation, as evaluated by Dt-apCO2. In addition, systemic and regional oxygen-derived variables do not reflect the regional microcirculation disturbances. Gastrointestinal tonometry clearly represents a useful tool for monitoring splanchnic perfusion in patients in hemodynamic shock.