Early hemodynamics and metabolic changes after total abdominal evisceration for experimental multivisceral transplantation / Efeitos hemodinâmicos e metabólicos iniciais da evisceração abdominal total para transplante multivisceral experimental

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...

Experimental models of sepsis and septic shock: an overview

Sepsis remains a major cause of morbidity and mortality in surgical patients and trauma victims, mainly due to sepsis-induced multiple organ dysfunction. In contrast to preclinical studies, most clinical trials of promising new treatment strategies for sepsis have fails to demonstrate efficacy. Although many reasons could account for this discrepancy, the misinterpretation of preclinical data obtained from experimental studies, and especially the use of animal models that do not adequately mimic human sepsis may have been contributing factors. In this review, the benefits and limitations of various animal models of sepsis are discussed to clarify the extend to which findings are relevant to human sepsis, particularly with respect to the subsequent design and execution of clinical trials. Such models include intravascular infusion of endotoxin or live bacteria, bacterial peritonitis, cecal ligation and perforation, soft tissue infection, pneumonia or meningitis models, using different animal species including rats, mice, rabbits, dogs, pigs, sheep and nonhuman primates. Despite several limitations, animal models remain essential in the development of all new therapies for sepsis and septic shock, because they provide fundamental information about the pharmacokinetics, toxicity, and mechanism of drug action that cannot be duplicated by other methods. New therapeutic agents should be studies in infection models, even after the initiation of the septic process. Furthermore, debility conditions need to be reproduced to avoid the exclusive use of healthy animals, which often do not represent the human septic patient.