Mechanisms of circulatory and intestinal barrier dysfunction during whole body hyperthermia

Hall, David; Buettner, Garry R.; Oberley, Larry W.; Xu, Honghui; Matthes, R. D.; Gisolfi, C. V.

doi:10.1152/ajpheart.2001.280.2.h509

Cited by 392 publications

(380 citation statements)

References 40 publications

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“…On the level of the whole organism, severe heat stress (42-43 °C for ~70 min) caused hyperthermia (i.e., body core temperature >40 °C), hypotension (mean arterial pressure <50 mmHg), intracranial hypertension, splanchnic vasoconstriction, and hypoxia, which might facilitate the leakage of endotoxin from the intestine to the systemic circulation and result in excessive activation of PMN cells and endothelial cells [1,2,21] . In this study, mild heat stress (36 °C for 100 min) also caused hyperthermia, hypotension, and many aspects of heatstroke reactions, described below.…”

Section: Discussionmentioning

confidence: 99%

Melatonin reduces acute lung inflammation, edema, and hemorrhage in heatstroke rats

Wu¹,

Chou²,

Chao

et al. 2012

Acta Pharmacol Sin

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Aim: To assess the therapeutic effect of melatonin on heat-induced acute lung inflammation and injury in rats. Methods: Heatstroke was induced by exposing anesthetized rats to heat stress (36 °C, 100 min). Rats were treated with vehicle or melatonin (0.2, 1, 5 mg/kg) by intravenous administration 100 min after the initiatioin of heatstroke and were allowed to recover at room temperature (26 °C). The acute lung injury was quantified by morphological examination and by determination of the volume of pleural exudates, the number of polymorphonuclear (PMN) cells, and the myeloperoxidase (MPO) activity. The concentrations of tumor necrosis factor, interleukin (IL)-1β, IL-6, and IL-10 in bronchoalveolar fluid (BALF) were measured by ELISA. Nitric oxide (NO) level was determined by Griess method. The levels of glutamate and lactate-to-pyruvate ratio were analyzed by CMA600 microdialysis analyzer. The concentrations of hydroxyl radicals were measured by a procedure based on the hydroxylation of sodium salicylates leading to the production of 2,3-dihydroxybenzoic acid (DHBA). Results: Melatonin (1 and 5 mg/kg ) significantly (i) prolonged the survival time of heartstroke rats (117 and 186 min vs 59 min); (ii) attenuated heatstroke-induced hyperthermia and hypotension; (iii) attenuated acute lung injury, including edema, neutrophil infiltration, and hemorrhage scores; (iv) down-regulated exudate volume, BALF PMN cell number, and MPO activity; (v) decreased the BALF levels of lung inflammation response cytokines like TNF-alpha, interleukin (IL)-1β, and IL-6 but further increased the level of an antiinflammatory cytokine IL-10; (vi) reduced BALF levels of glutamate, lactate-to-pyruvate ratio, NO, 2,3-DHBA, and lactate dehydrogenase. Conclusion: Melatonin may improve the outcome of heatstroke in rats by attenuating acute lung inflammation and injury.

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Section: Discussionmentioning

confidence: 99%

Melatonin reduces acute lung inflammation, edema, and hemorrhage in heatstroke rats

Wu¹,

Chou²,

Chao

et al. 2012

Acta Pharmacol Sin

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“…3,5,68 High sensitivity to hyperthermia, ischemia, and hypoxia of canine gastrointestinal tract has also been observed, 66 and inflammatory cytokines and reactive oxygen and nitrogen species generated by the intestinal injured tissue may exacerbate mucosal damage, resulting in necrosis and hyperpermeability with subsequent potential for bacterial translocation and leakage of endotoxins into the bloodstream. 1,3,18,69,70 The capillary and venous endothelia are also very susceptible to direct thermal injury, which in association with endotoxemia and cytokine production, may lead to increased vascular permeability and consequently to edema. Widespread endothelial damage may also result in tissue thromboplastin and factor XII release, with consequent activation of the coagulation and complement cascades, which may culminate in systemic inflammatory response syndrome (SIRS) and widespread microthrombosis and hemorrhagic diathesis as a result of disseminated intravascular coagulation (DIC).…”

Section: Pathophysiology Of Heatstrokementioning

confidence: 99%

Pathophysiology and pathological findings of heatstroke in dogs

Romanucci¹,

Salda²

2013

VMRR

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Canine heatstroke is a life-threatening condition resulting from an imbalance between heat dissipation and production, and characterized by a nonpyrogenic elevation in core body temperature above 41°C (105.8°F). Several exogenous and endogenous factors may predispose dogs to the development of heatstroke; on the other hand, adaptive mechanisms also exists which allow organisms to combat the deleterious effects of heat stress, which are represented by the cellular heat-shock response and heat acclimatization. The pathophysiology and consequences of heatstroke share many similarities to those observable in sepsis and are related to the interaction between the direct cytotoxicity of heat, the acute physiological alterations associated with hyperthermia, such as increased metabolic demand, hypoxia, and circulatory failure, and the inflammatory and coagulation responses of the host to the widespread endothelial and tissue injuries, which may culminate in disseminated intravascular coagulation, systemic inflammatory response syndrome, and multiple organ dysfunction.

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“…However, 85 min after the start of heat stress, the Tco and MAP reached new values of about 41 °C and about 40 mmHg, respectively. The instant (85 min after heat exposure) in which Tco rose above 41 °C and MAP dropped about 40 mmHg was arbitrarily defined as the time point for the onset of heatstroke [3,11,12] . At 68 min, the heating pad was removed, and the animals were allowed to recover at room temperature (26 °C KYNA protected against hypotension but not hyperthermia during heatstroke As shown in this Figure 1, heat stress induced significant (P<0.05) increase in both Tco and MAP in vehicle-treated heatstroke rats at 68 min.…”

Section: Kyna Prolonged Survival Time Values During Heatstrokementioning

confidence: 99%

Kynurenic acid attenuates multiorgan dysfunction in rats after heatstroke

Hsieh

Chen

Yeh³

et al. 2011

Acta Pharmacol Sin

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IntroductionHeatstroke is defined as a form of excessive hyperthermia (>40 °C) associated with a systemic inflammatory response that leads to multi-organ dysfunction in which central nervous system (CNS) disorders such as delusion, convulsion and coma predominate [1] . Our recent results have demonstrated that heatstroke rodents display hypotension, systemic inflammatory responses, hypothalamic ischemia and neuronal damage, and multi-organ dysfunction [2][3][4] .Kynurenic acid (KYNA) or its metabolic precursor L-kynurenine may be of therapeutic value in neurodegenerative diseased models [5,6] . For example, systemically administered high doses of KYNA had a neuroprotective effect in the gerbil model of global ischemia [7] . Both the homocysteine-induced impairment of endothelial cells [8] and the motility and inflammatory activation in the early phase of acute experimental colitis in the rat [9] were significantly reduced by administration of KYNA. The aim of this study was to investigate whether the heatstroke induced hypotension, systemic inflammatory responses, hypothalamic ischemia and damage, and multiorgan dysfunction could be attenuated by KYNA preconditioning. Accordingly, the temporal profiles of the apoptotic cell numbers of spleen, kidney, liver, lung, and hypothalamus, Kynurenic acid attenuates multiorgan dysfunction in rats after heatstroke Aim: To assess whether systemic delivery of kynurenic acid improves the outcomes of heatstroke in rats. Methods: Anesthetized rats were divided into 2 major groups and given vehicle solution (isotonic saline 0.3 mL/kg rat weight) or kynurenic acid (30-100 mg in 0.3 mL saline/kg) 4 h before the start of thermal experiments. They were exposed to an ambient temperature of 43 ºC for 68 min to induce heatstroke. Another group of rats were exposed to room temperature (26 ºC) and used as normothermic controls. Their core temperatures, mean arterial pressures, serum levels of systemic inflammatory response molecules, hypothalamic values of apoptotic cells and neuronal damage scores, and spleen, liver, kidney and lung values of apoptotic cells were determined. Results: The survival time values during heatstroke for vehicle-treated rats were decreased from the control values of 475-485 min to new values of 83-95 min. Treatment with KYNA (30-100 mg/kg, iv) 4 h before the start of heat stress significantly and dose-dependently decreased the survival time to new values of 152-356 min (P<0.05). Vehicle-treated heatstroke rats displayed hypotension, hypothalamic neuronal degeneration and apoptosis, increased serum levels of tunor necrosis factor-α (TNF-α), intercellular adhesion molecule-1 (ICAM-1), and interleukin-10 (IL-10), and spleen, liver, kidney, and lung apoptosis. KYNA preconditioning protected against hypotension but not hyperthermia and attenuated hypothalamic neuronal degeneration and apoptosis during heatstroke. KYNA preconditioning attenuated spleen, kidney, liver, and lung apoptosis and up-regulated serum IL-10 levels but down-regulated serum TNF-α and ICAM-1 lev...

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Mechanisms of circulatory and intestinal barrier dysfunction during whole body hyperthermia

Cited by 392 publications

References 40 publications

Melatonin reduces acute lung inflammation, edema, and hemorrhage in heatstroke rats

Melatonin reduces acute lung inflammation, edema, and hemorrhage in heatstroke rats

Pathophysiology and pathological findings of heatstroke in dogs

Kynurenic acid attenuates multiorgan dysfunction in rats after heatstroke

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