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- Chew, Michelle, et al.
(författare)
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Depletion of myocardial glucose is observed during endotoxemic but not hemorrhagic shock in a porcine model
- 2013
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Ingår i: Critical Care. - : Springer Science and Business Media LLC. - 1364-8535. ; 17:4
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Tidskriftsartikel (refereegranskat)abstract
- Introduction Metabolic dysfunction is one of the hallmarks of sepsis yet little is known about local changes in key organs such as the heart. The aim of this study was to compare myocardial metabolic changes by direct measurements of substrates, such as glucose, lactate and pyruvate, using microdialysis (MD) in in-vivo porcine endotoxemic and hemorrhagic shock. To assess whether these changes were specific to the heart, we simultaneously investigated substrate levels in skeletal muscle. Methods Twenty-six female pigs were randomized to three groups: control (C) n = 8, endotoxemic shock (E) n = 9 and hemorrhagic shock (H) n = 9. Interstitial myocardial pyruvate, lactate and glucose were measured using MD. Skeletal muscle MD was also performed in all three groups. Results Marked decreases in myocardial glucose were observed in the E group but not in the H group compared to controls (mean difference (CI) in mmol/L: C versus E -1.5(-2.2 to -0.8), P < 0.001; H versus E -1.1(-1.8 to -0.4), P = 0.004; C versus H -0.4(-1.1 to 0.3), P = 0.282). Up to four-fold increases in myocardial pyruvate and three-fold increases in lactate were seen in both shock groups with no differences between the two types of shock. There was no evidence of myocardial anaerobic metabolism, with normal lactate: pyruvate (L:P) ratios seen in all animals regardless of the type of shock. In skeletal muscle, decreases in glucose concentrations were observed in the E group only (mean difference: C versus E -0.8(-1.4 to -0.3), P = 0.007). Although skeletal muscle lactate increased in both shock groups, this was accompanied by increases in pyruvate in the E group only (mean difference: C versus E 121(46 to 195), P = 0.003; H versus E 77(7 to 147), P = 0.032; C versus H 43(-30 to 43), P = 0.229). The L:P ratio was increased in skeletal muscle in response to hemorrhagic, but not endotoxemic, shock. Conclusions Endotoxemia, but not hemorrhage, induces a rapid decrease of myocardial glucose levels. Despite the decrease in glucose, myocardial lactate and pyruvate concentrations were elevated and not different than in hemorrhagic shock. In skeletal muscle, substrate patterns during endotoxemic shock mimicked those seen in myocardium. During hemorrhagic shock the skeletal muscle response was characterized by a lack of increase in pyruvate and higher L: P ratios. Hence, metabolic patterns in the myocardium during endotoxemic shock are different than those seen during hemorrhagic shock. Skeletal muscle and myocardium displayed similar substrate patterns during endotoxemic shock but differed during hemorrhagic shock.
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| 2. |
- Rocklöv, Joacim, et al.
(författare)
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On the estimation of heat-intensity and heat-duration effects in time series models of temperature-related mortality in Stockholm, Sweden
- 2012
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Ingår i: Environmental Health. - 1476-069X. ; 11, s. 23-
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Tidskriftsartikel (refereegranskat)abstract
- Background: We examine the effect of heat waves on mortality, over and above what would be predicted on the basis of temperature alone.Methods: Present modeling approaches may not fully capture extra effects relating to heat wave duration, possibly because the mechanisms of action and the population at risk are different under more extreme conditions. Modeling such extra effects can be achieved using the commonly left-out effect-modification between the lags of temperature in distributed lag models.Results: Using data from Stockholm, Sweden, and a variety of modeling approaches, we found that heat wave effects amount to a stable and statistically significant 8.1-11.6% increase in excess deaths per heat wave day. The effects explicitly relating to heat wave duration (2.0-3.9% excess deaths per day) were more sensitive to the degrees of freedom allowed for in the overall temperature-mortality relationship. However, allowing for a very large number of degrees of freedom indicated over-fitting the overall temperature-mortality relationship.Conclusions: Modeling additional heat wave effects, e. g. between lag effect-modification, can give a better description of the effects from extreme temperatures, particularly in the non-elderly population. We speculate that it is biologically plausible to differentiate effects from heat and heat wave duration.
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