Experimental Models of Hemorrhagic Shock: A Review

Fülöp, András; Turóczi, Z.; Garbaisz, D.; Harsányi, L; Szijártó, A

doi:10.1159/000348808

Cited by 72 publications

(51 citation statements)

References 218 publications

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“…The model we used achieved reliable and relevant changes in macro- and microcirculatory values during hemorrhage [44,45]. A dog's spleen is considered to function as a blood reservoir, increasing circulating blood volume and thereby counteracting acute hemorrhage [46] but in nonlethal, fixed-volume canine hemorrhage, splenectomy seems to be of minor importance. During the hemorrhage period, there were no differences observed between spleen-intact and splenectomized dogs concerning HR, MAP, and dO 2 [47].…”

Section: Discussionmentioning

confidence: 99%

Effect of Topical Iloprost and Nitroglycerin on Gastric Microcirculation and Barrier Function during Hemorrhagic Shock in Dogs

et al. 2017

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Background: Topical drug application is used to avoid systemic side effects. The aim of this study was to analyze whether locally applied iloprost or nitroglycerin influence gastric mucosal perfusion, oxygenation, and barrier function during physiological and hemorrhagic conditions. Methods: In repeated experiments, 5 anesthetized dogs received iloprost, nitroglycerin, or normal saline during physiological and hemorrhagic (-20% blood volume) conditions. Macro- and microcirculatory variables were recorded continuously. Gastric barrier function was assessed via translocation of sucrose into the blood. Results: During hemorrhage, gastric mucosal oxygenation decreased from 77 ± 4 to 37 ± 7%. This effect was attenuated by nitroglycerin (78 ± 6 to 47 ± 13%) and iloprost (82 ± 4 to 54 ± 9%). Sucrose plasma levels increased during hemorrhage from 7 ± 4 to 55 ± 15 relative amounts. This was alleviated by nitroglycerin (5 ± 8 to 29 ± 38 relative amounts). These effects were independent of systemic hemodynamic variables. Conclusions: During hemorrhage, topical nitroglycerin and iloprost improve regional gastric oxygenation without affecting perfusion. Nitroglycerin attenuated the shock-induced impairment of the mucosal barrier integrity. Thus, local drug application improves gastric microcirculation without compromising systemic hemodynamic variables, and it may also protect mucosal barrier function.

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Section: Discussionmentioning

confidence: 99%

Effect of Topical Iloprost and Nitroglycerin on Gastric Microcirculation and Barrier Function during Hemorrhagic Shock in Dogs

et al. 2017

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“…As detailed by Fülöp and colleagues [26], this model has the advantage of being highly standardized, controlled and reproducible, and as such is optimal for the study of the pathophysiology and proteomics/peptidomics of shock. In particular: i) the controlled procedure for blood withdrawal and return (executed at the same rate of 0.5 cc/min, as explained in the Materials and Methods) is completely reproducible; ii) the objective control of the hemodynamic state of the animal during hypovolemia is ensured by the maintenance of blood pressure around the target value of 35 mmHg; iii) the monitoring of conditions such as body temperature (decreased following bleeding, constant throughout the hypovolemic phase, and increased again to physiologic levels upon reperfusion) is conveniently repeatable.…”

Section: Discussionmentioning

confidence: 99%

Peptidomic Analysis of Rat Plasma

Aletti

Maffioli

Negri

et al. 2016

Shock

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It has been previously shown that intestinal proteases translocate into the circulation during hemorrhagic shock and contribute to proteolysis in distal organs. However, consequences of this phenomenon have not previously been investigated using high-throughput approaches. Here, a shotgun label-free quantitative proteomic approach was utilized to compare the peptidome of plasma samples from healthy and hemorrhagic shock rats to verify the possible role of uncontrolled proteolytic activity in shock. Plasma was collected from rats after hemorrhagic shock (HS) consisting of two-hour hypovolemia followed by two-hour reperfusion, and from healthy control (CTRL) rats. A new two-step enrichment method was applied to selectively extract peptides and low molecular weight proteins from plasma, and directly analyze these samples by tandem mass spectrometry. 126 circulating peptides were identified in CTRL and 295 in HS animals. 96 peptides were present in both conditions; of these, 57 increased and 30 decreased in shock. In total, 256 peptides were increased or present only in HS confirming a general increase in proteolytic activity in shock. Analysis of the proteases that potentially generated the identified peptides suggests that the larger relative contribution of to the proteolytic activity in shock is due to chymotryptic-like proteases. These results provide quantitative confirmation that extensive, system-wide proteolysis is part of the complex pathologic phenomena occurring in hemorrhagic shock.

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“…To test this hypothesis and expand on our previous observations in rodent models, we employed a porcine model of TI, in the presence or absence of HS. This represents a better translational model for higher mammals and thus for clinical translatability 20 . We hypothesized that the study of differential models of TI and HS would produce distinct metabolic signatures in plasma.…”

Section: Introductionmentioning

confidence: 99%

Hemorrhagic shock and tissue injury drive distinct plasma metabolome derangements in swine

Clendenen

Nunns

Moore

et al. 2017

Journal of Trauma and Acute Care Surgery

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Background Tissue injury and hemorrhagic shock induce significant systemic metabolic reprogramming in animal models and critically injured patients. Recent expansions of the classic concepts of metabolomic aberrations in tissue injury and hemorrhage opened the way for novel resuscitative interventions based on the observed abnormal metabolic demands. We hypothesize that metabolic demands and resulting metabolic signatures in pig plasma will vary in response to isolated or combined tissue injury and hemorrhagic shock. Methods A total of 20 pigs underwent either isolated tissue injury, hemorrhagic shock, or combined tissue injury and hemorrhagic shock referenced to a sham protocol (n=5/group). Plasma samples were analyzed by UHPLC-MS. Results Hemorrhagic shock promoted a hypermetabolic state. Tissue injury alone dampened metabolic responses in comparison to sham and hemorrhagic shock, and attenuated the hypermetabolic state triggered by shock with respect to energy metabolism (glycolysis, glutaminolysis and Krebs cycle). Tissue injury and hemorrhagic shock had a more pronounced effect on nitrogen metabolism (arginine, polyamines and purine metabolism) than hemorrhagic shock alone. Conclusion Isolated or combined tissue injury and hemorrhagic shock result in distinct plasma metabolic signatures. These findings indicate that optimized resuscitative interventions in critically ill patients is possible based on identifying the severity of tissue injury and hemorrhage.

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Experimental Models of Hemorrhagic Shock: A Review

Cited by 72 publications

References 218 publications

Effect of Topical Iloprost and Nitroglycerin on Gastric Microcirculation and Barrier Function during Hemorrhagic Shock in Dogs

Effect of Topical Iloprost and Nitroglycerin on Gastric Microcirculation and Barrier Function during Hemorrhagic Shock in Dogs

Peptidomic Analysis of Rat Plasma

Hemorrhagic shock and tissue injury drive distinct plasma metabolome derangements in swine

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