Genetic Predisposition for High- or Low-Exercise Capacity Does Not Affect the Detrimental Impact of Sepsis in Rats

Objectives: Sepsis is a systemic inflammatory reaction that may lead to multiple organ failure and death. Sepsis-induced cardiac dysfunction represents one important complication and is coresponsible for the high mortality typical for sepsis. Physical fitness, as well as high-intrinsic exercise capacity positively, influences cardiovascular health. However, less is known about the impact of these factors on cardiac performance and metabolism in sepsis. We aimed to identify the effect of sepsis on cardiac function, metabolism and insulin responsiveness in rats differing in their genetic predisposition for either high or low inborn exercise capacity.

Methods: Sepsis was induced in 15-week old rats with high (HCR) or low (LCR) intrinsic running capacity by intraperitoneal injection of a human fecal suspension. The clinical severity score (CSS) was determined to assess sepsis severity 6 and 24 hours later. At 1 and 5 weeks, hearts were excised and prepared as isolated working hearts. Cardiac function, substrate oxidation, and response to insulin were measured using radioactive tracer technology.

Results: The two groups did not differ in their CCS scores at 6 and 24 hours and survival was poor with 33% (HCR) and 38% (LCR) survivors at 72 hours. After 5 weeks, septic animals displayed substantial reductions of cardiac power in LCR and HCR (LCR control vs. LCR 5 weeks and HCR control vs. HCR 5 weeks: 46.1 ± 5.0 vs. 35.31 ± 2.1, p = 0.07, and 44.8 ± 3.3 vs. 40.5 ± 1.6 mW/g dry). This reduction in power was not associated with sepsis-induced alterations in glucose oxidation (0.41 ± 0.1 vs. 0.33 ± 0.09 and 0.23 ± 0.01 vs. 0.24 ± 0.04 μmol/min/g dry, n.s.) or fatty acid oxidation (0.61 ± 0.11 vs. 0.76 ± 0.08 and 0.73 ± 0.13 vs. 0,99 ± 0.36 μmol/min/g dry, n.s.). However, when relating substrate oxidation to cardiac power as a measure of substrate efficacy, there was a significant increase in substrate used per force. Insulin response was increased in HCR only (change of glucose oxidation: +0.32 ± 0.08 vs. +0.39 ± 0.07 and +0.16 ± 0.04 vs. +0.51 ± 0.11 μmol/min/g dry, p < 0.05).

Conclusion: The detrimental effects of sepsis on survival in rats are not affected by their genetically determined exercise capacity. Sepsis causes significant mortality and contractile dysfunction in survivors. This dysfunction was accompanied by maintained glucose and fatty acid oxidation suggesting significantly decreased efficiency of substrate use.

No conflict of interest has been declared by the author(s).