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Depletion of myocardial glucose is observed during endotoxemic but not hemorrhagic shock in a porcine model.

Chew MS, Shekar K, Brand BA, Norin C, Barnett AG - Crit Care (2013)

Bottom Line: Skeletal muscle MD was also performed in all three groups.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).Endotoxemia, but not hemorrhage, induces a rapid decrease of myocardial glucose levels.

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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.

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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A) Myocardial and B) skeletal muscle glucose concentrations. t0 refers to baseline measurements prior to induction of endotoxemic or hemorrhagic shock. Significant decreases over time were seen in the myocardium during endotoxemic but not hemorrhagic shock compared to controls (P <0.001). There was a similar decrease in skeletal muscle during endotoxemic shock (P = 0.007) but not during hemorrhagic shock. Significant differences for individual time points are marked * for C versus H, + for C versus E, x for H versus E. C, control group; E, endotoxemic group; H, hemorrhagic group.
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Figure 1: A) Myocardial and B) skeletal muscle glucose concentrations. t0 refers to baseline measurements prior to induction of endotoxemic or hemorrhagic shock. Significant decreases over time were seen in the myocardium during endotoxemic but not hemorrhagic shock compared to controls (P <0.001). There was a similar decrease in skeletal muscle during endotoxemic shock (P = 0.007) but not during hemorrhagic shock. Significant differences for individual time points are marked * for C versus H, + for C versus E, x for H versus E. C, control group; E, endotoxemic group; H, hemorrhagic group.

Mentions: Marked decreases in myocardial glucose were observed in the E group towards the end of the study period (nadir 0.6 (0.5 to 0.8) mmol/L, P <0.001 compared to baseline) whereas they remained relatively stable in the H group (Figure 1a). There were significant mean differences between C versus E (P <0.001) and H versus E groups (P = 0.004). Post-hoc analysis revealed significant differences between C and E animals and between H and E animals from t3 onwards. No difference was seen for the C versus H group. Increases in myocardial pyruvate were seen in all animals, with four-fold increases observed in H and E shock groups (Figure 2a). There were significant mean differences between the C and E groups (P <0.001) and between the C and H groups (P <0.001) but not between the H and E animals. Myocardial lactate levels also increased in both shock groups (Figure 3a). Significant mean differences were seen between the C and E groups (P = 0.032) and between the C and H groups (P = 0.016). There were no differences between the E and H groups. The myocardial-A-lac gradient was significantly increased in the E compared to the H group (mean difference H versus E 0.7 (CI 0 to 1.3) mmol/L, P = 0.04) but was not significantly different from the C group (mean difference C versus E -0.3 (CI -1.0 to 0.3) mmol/L, P = 0.299). The L:P ratio over time decreased significantly in all animals, indicating no evidence of myocardial anaerobic metabolism (Figure 4a).


Depletion of myocardial glucose is observed during endotoxemic but not hemorrhagic shock in a porcine model.

Chew MS, Shekar K, Brand BA, Norin C, Barnett AG - Crit Care (2013)

A) Myocardial and B) skeletal muscle glucose concentrations. t0 refers to baseline measurements prior to induction of endotoxemic or hemorrhagic shock. Significant decreases over time were seen in the myocardium during endotoxemic but not hemorrhagic shock compared to controls (P <0.001). There was a similar decrease in skeletal muscle during endotoxemic shock (P = 0.007) but not during hemorrhagic shock. Significant differences for individual time points are marked * for C versus H, + for C versus E, x for H versus E. C, control group; E, endotoxemic group; H, hemorrhagic group.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4231428&req=5

Figure 1: A) Myocardial and B) skeletal muscle glucose concentrations. t0 refers to baseline measurements prior to induction of endotoxemic or hemorrhagic shock. Significant decreases over time were seen in the myocardium during endotoxemic but not hemorrhagic shock compared to controls (P <0.001). There was a similar decrease in skeletal muscle during endotoxemic shock (P = 0.007) but not during hemorrhagic shock. Significant differences for individual time points are marked * for C versus H, + for C versus E, x for H versus E. C, control group; E, endotoxemic group; H, hemorrhagic group.
Mentions: Marked decreases in myocardial glucose were observed in the E group towards the end of the study period (nadir 0.6 (0.5 to 0.8) mmol/L, P <0.001 compared to baseline) whereas they remained relatively stable in the H group (Figure 1a). There were significant mean differences between C versus E (P <0.001) and H versus E groups (P = 0.004). Post-hoc analysis revealed significant differences between C and E animals and between H and E animals from t3 onwards. No difference was seen for the C versus H group. Increases in myocardial pyruvate were seen in all animals, with four-fold increases observed in H and E shock groups (Figure 2a). There were significant mean differences between the C and E groups (P <0.001) and between the C and H groups (P <0.001) but not between the H and E animals. Myocardial lactate levels also increased in both shock groups (Figure 3a). Significant mean differences were seen between the C and E groups (P = 0.032) and between the C and H groups (P = 0.016). There were no differences between the E and H groups. The myocardial-A-lac gradient was significantly increased in the E compared to the H group (mean difference H versus E 0.7 (CI 0 to 1.3) mmol/L, P = 0.04) but was not significantly different from the C group (mean difference C versus E -0.3 (CI -1.0 to 0.3) mmol/L, P = 0.299). The L:P ratio over time decreased significantly in all animals, indicating no evidence of myocardial anaerobic metabolism (Figure 4a).

Bottom Line: Skeletal muscle MD was also performed in all three groups.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).Endotoxemia, but not hemorrhage, induces a rapid decrease of myocardial glucose levels.

View Article: PubMed Central - HTML - PubMed

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.

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.

Show MeSH
Related in: MedlinePlus