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Temperature sensitivity of glycolysis during sepsis
Philippe Sébert1, Christophe Kervran, Erwan L'Her
1Laboratoire de Physiologie, Unité Haute Pression et Métabolism, Faculté de Médecine, CHU de la Cavale Blanche, Brest Cedex, France.
Objective:
To investigate the temperature sensitivity of glycolysis during sepsis.
Design:
A prospective, randomized, controlled animal study.
Setting:
The Physiological Department of a University Hospital.
Subjects:
Ten male Sprague-Dawley rats, weighing 400-500 g.
Interventions:
The rats were assigned to either a septic (n = 5) or a sham-control group (n = 5). After anesthesia (H0), experimental sepsis was induced by a cecal ligation and perforation, and the left lateral gastrocnemius was sampled. Four hours later (H4), a second anesthesia was performed to sample the contralateral muscle. The sham-control group underwent the same procedures, but the cecum was neither ligated nor incised.
Measurements And Main Results:
Glycolytic flux (J(B), the rate at which glycogen can be used in muscle) and the transition time (t99 : the time required for the transition from aerobic to anaerobic metabolism) were measured by using spectrophotometry. The measurements were performed at seven different temperature levels, ranging from 32 to 42 degrees C. For each measured variable, the temperature sensitivity of glycolysis was assessed by computing the Q10 values, which is the variation ratio of the measured variable, attributed to a 10 degrees C temperature increase. In control rats, anesthesia and surgical procedures induced a J(B) increase (7.9 +/- 1.6 at H0 vs. 11.9 +/- 2.1 micromol x min-1 x g(tissue) at H4, p<.05) without any t99 variation. Whatever the group (control or septic), the same temperature variation induced an effect that was approximately three times higher in the hypothermia (<37 degrees C) than in the hyperthermia range (>37 degrees C; p<.05). However, a loss in thermal sensitivity was observed in septic rats in the hyperthermia range (Q10 = 1.2 +/- 0.1 for septic animals vs. 2.3 +/- 0.4 for control animals; p<.05).
Conclusions:
This study demonstrates that glycolysis is more sensitive to temperature in the hypothermia range than in the hyperthermia range. The loss in thermal sensitivity at >37 degrees C in septic rats suggests that sepsis may induce a dysregulation of glycolysis. From an energetic point of view, this signifies that hyperthermia may by itself impair energy metabolism without improving energy production and thus must be treated during sepsis.