Early Myocardial Dysfunction is Not Caused by Mitochondrial Abnormalities in a Rat Model of Peritonitis

Smeding, Lonneke; Laarse, Willem J. van der; Veelen, T. A. van; Lamberts, Regis R.; Niessen, Hans W.M.; Kneyber, Martin C. J.; Groeneveld, A. B. Johan; Plötz, Frans B.

doi:10.1016/j.jss.2011.05.055

Cited by 13 publications

(10 citation statements)

References 42 publications

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“…However, support for a Ca 2+ -independent role of CXC1 in myocardial dysfunction, as suggested by our study, comes from another report [26,41] and inhibition of CXCL1 decreases right ventricular failure in a model of pulmonary embolism [42]. In any case, myocardial expression of other inflammatory mediators was not increased, which might be due to a different time course of expression: TNF-α expression is increased 2 hours after LPS exposure, but not detectable anymore after 4 hours [14]. …”

Section: Discussionsupporting

confidence: 63%

“…It may thus be postulated that the HSP response following MV in the absence of LPS in our model is dependent upon both the degree of lung injury, the inflammatory response and their time course, so that we may have missed upregulation of HSP70 in the high V t control group [38,39]. We have previously observed such a time course for TNF-α in a rat model of endotoxaemia-induced peritonitis [14]. This aspect warrants further investigation.…”

Section: Discussionmentioning

confidence: 99%

“…Five minutes after LPS administration, the protocol was started and animals were randomly assigned to one of two ventilation strategies; ventilation with either low V t (6 ml/kg, 5 cm H 2 O PEEP) which is regarded as a lung protective strategy [19], or high V t (19 ml/kg, 1 cm H 2 O PEEP) which is regarded as an injurious strategy [20,21]. Ventilatory settings were chosen such that mean airway pressure was similar to avoid differences among groups in cardiac preloading [5,14]. Thus four groups were studied; non-LPS treated (n=8) and LPS-treated animals (n=8) ventilated with low V t and non-LPS treated (n=11, including N = 3 animals not included in the Langendorff setup because of technical issues) and LPS-treated animals (n=8) ventilated with high V t .…”

Section: Methodsmentioning

confidence: 99%

“…Sepsis may hamper both pulmonary function [10], thereby necessitating MV, and myocardial function [11-14]. Sepsis may be associated with myocardial inflammation and a decrease in myocardial calcium (Ca 2+ ) handling and sensitivity, thereby potentially contributing to impaired myocardial function [12,13].…”

Section: Introductionmentioning

confidence: 99%

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Aggravation of myocardial dysfunction by injurious mechanical ventilation in LPS-induced pneumonia in rats

et al. 2013

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BackgroundMechanical ventilation (MV) may cause ventilator-induced lung injury (VILI) and may thereby contribute to fatal multiple organ failure. We tested the hypothesis that injurious MV of lipopolysaccharide (LPS) pre-injured lungs induces myocardial inflammation and further dysfunction ex vivo, through calcium (Ca2+)-dependent mechanism.Materials and methodsN = 35 male anesthetized and paralyzed male Wistar rats were randomized to intratracheal instillation of 2 mg/kg LPS or nothing and subsequent MV with lung-protective settings (low tidal volume (Vt) of 6 mL/kg and 5 cmH2O positive end-expiratory pressure (PEEP)) or injurious ventilation (high Vt of 19 mL/kg and 1 cmH2O PEEP) for 4 hours. Myocardial function ex vivo was evaluated in a Langendorff setup and Ca2+ exposure. Key mediators were determined in lung and heart at the mRNA level.ResultsInstillation of LPS and high Vt MV impaired gas exchange and, particularly when combined, increased pulmonary wet/dry ratio; heat shock protein (HSP)70 mRNA expression also increased by the interaction between LPS and high Vt MV. For the heart, C-X-C motif ligand (CXCL)1 and Toll-like receptor (TLR)2 mRNA expression increased, and ventricular (LV) systolic pressure, LV developed pressure, LV +dP/dtmax and contractile responses to increasing Ca2+ exposure ex vivo decreased by LPS. High Vt ventilation aggravated the effects of LPS on myocardial inflammation and dysfunction but not on Ca2+ responses.ConclusionsInjurious MV by high Vt aggravates the effects of intratracheal instillation of LPS on myocardial dysfunction, possibly through enhancing myocardial inflammation via pulmonary release of HSP70 stimulating cardiac TLR2, not involving Ca2+ handling and sensitivity.

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Section: Discussionsupporting

confidence: 63%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Aggravation of myocardial dysfunction by injurious mechanical ventilation in LPS-induced pneumonia in rats

et al. 2013

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“…Although early myocardial dysfunction during sepsis is associated with myocardial inflammation rather than mitochondrial injury [ 87 ], enzyme activities of nicotinamide-adenine dinucleotid cytochrome c reductase, succinate cytochrome c reductase and cytochrome c oxidase were found to be significantly suppressed during sepsis. Mitochondrial complex II and complex IV were also downregulated, and the myocardial ATP content markedly declined during the late stage of sepsis [ 88 ].…”

Section: Pathogenesis Of Simdmentioning

confidence: 99%

Pathophysiology of sepsis-induced myocardial dysfunction

2016

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Sepsis-induced myocardial dysfunction is a common complication in septic patients and is associated with increased mortality. In the clinical setting, it was once believed that myocardial dysfunction was not a major pathological process in the septic patients, at least in part, due to the unavailability of suitable clinical markers to assess intrinsic myocardial function during sepsis. Although sepsis-induced myocardial dysfunction has been studied in clinical and basic research for more than 30 years, its pathophysiology is not completely understood, and no specific therapies for this disorder exist. The purpose of this review is to summarize our current knowledge of sepsis-induced myocardial dysfunction with a special focus on pathogenesis and clinical characteristics.

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Myocardial mechanical dysfunction following endotoxemia: role of changes in energy substrate metabolism

et al. 2016

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Cardiovascular depression due to endotoxemia remains a major cause of mortality in intensive care patients. To determine whether drug-induced alterations in cardiac metabolism may be a viable strategy to reduce endotoxemia-mediated cardiac dysfunction, we assessed endotoxemia-induced changes in glucose and fatty acid metabolism under aerobic and post-ischemic conditions. Endotoxemia was induced in male Sprague-Dawley rats by lipopolysaccharide (Escherichia coli 0111:B4c, 4 mg/kg, i.p.) 6 h prior to heart removal for ex vivo assessment of left ventricular (LV) work and rates of glucose metabolism (glucose uptake, glycogen synthesis, glycolysis and glucose oxidation) and palmitate oxidation. Under aerobic conditions, endotoxemic hearts had impaired LV function as judged by echocardiography in vivo (% ejection fraction, 66.0 ± 3.2 vs 78.0 ± 2.1, p < 0.05) or by LV work ex vivo (2.14 ± 0.16 vs 3.28 ± 0.16, Joules min(-1) g dry wt(-1), p < 0.05). However, rates of glucose uptake, glycogen synthesis, glycolysis, and glucose oxidation were not altered. Palmitate oxidation was lower in endotoxemic hearts in proportion to the decreased workload, thus metabolic efficiency was unaffected. In hearts reperfused following global ischemia, untreated hearts had impaired recovery of LV work (52.3 ± 9.4 %) whereas endotoxemic hearts had significantly higher recovery (105.6 ± 11.3 %, p < 0.05). During reperfusion, fatty acid oxidation, acetyl CoA production and metabolic efficiency were similar in both groups. As impaired cardiac function appeared unrelated to depression of energy substrate oxidation, it is unlikely that drug-induced acceleration of fatty acid oxidation will improve mechanical function. The beneficial repartitioning of glucose metabolism in reperfused endotoxemic hearts may contribute to the cardioprotected phenotype.

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Early Myocardial Dysfunction is Not Caused by Mitochondrial Abnormalities in a Rat Model of Peritonitis

Cited by 13 publications

References 42 publications

Aggravation of myocardial dysfunction by injurious mechanical ventilation in LPS-induced pneumonia in rats

Aggravation of myocardial dysfunction by injurious mechanical ventilation in LPS-induced pneumonia in rats

Pathophysiology of sepsis-induced myocardial dysfunction

Myocardial mechanical dysfunction following endotoxemia: role of changes in energy substrate metabolism

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