Shock : molecular, cellular, and systemic pathobiological aspects and therapeutic approaches : the official journal the Shock Society, the European Shock Society, the Brazilian Shock Society, the International Federation of Shock Societies
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Given that the leading clinical conditions associated with acute kidney injury (AKI), namely, sepsis, major surgery, heart failure, and hypovolemia, are all associated with shock, it is tempting to attribute all AKI to ischemia on the basis of macrohemodynamic changes. However, an increasing body of evidence has suggested that in many patients, AKI can occur in the absence of overt signs of global renal hypoperfusion. ⋯ Herein, we put forward a "unifying theory" to explain the interplay between inflammation and oxidative stress, microvascular dysfunction, and the adaptive response of the tubular epithelial cell to the septic insult. We propose that this response is mostly adaptive in origin, that it is driven by mitochondria, and that it ultimately results in and explains the clinical phenotype of sepsis-induced AKI.
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Sepsis-induced cardiomyopathy (SIC), which is a common morbid condition, occurs in patients with severe sepsis and septic shock. The clinical characterization of SIC has been largely concept-driven. Heart function has traditionally been evaluated according to two basic conceptual models: a hydraulic pump system, whereby the output from the heart is entirely dependent on its input, or a hemodynamic pump, whereby the cardiac output is a function of preload, global ventricular performance, and afterload. ⋯ This review addresses the conceptual background, historical perspectives, physiologic mechanisms, current evidence, and limitations of SIC characterization. It also highlights potential future directions for the hemodynamic assessment of the intrinsic contractile function of the heart to overcome current methodological limitations. Finally, the present review recommends the exploration of additional potential mechanisms underlying SIC.
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In human trauma patients, most deaths result from hemorrhage and brain injury, whereas late deaths, although rare, are the result of multiple organ failure and sepsis. A variety of experimental animal models have been developed to investigate the pathophysiology of traumatic injury and evaluate novel interventions. Similar to other experimental models, these trauma models cannot recapitulate conditions of naturally occurring trauma, and therefore therapeutic interventions based on these models are often ineffective. ⋯ The American College of Veterinary Emergency and Critical Care Veterinary Committee on Trauma has initiated the establishment of a national network of veterinary trauma centers to enhance uniform delivery of care to canine trauma patients. In addition, the Spontaneous Trauma in Animals Team, a multidisciplinary, multicenter group of researchers has created a clinical research infrastructure for carrying out large-scale clinical trials in canine trauma patients. Moving forward, these national resources can be utilized to facilitate multicenter prospective studies of canine trauma to evaluate therapies and interventions that have shown promise in experimental animal models, thus closing the critical gap in the translation of knowledge from experimental models to humans and increasing the likelihood of success in phases 1 and 2 human clinical trials.