February 1, 2001American Journal of Respiratory and Critical Care Medicine
Phosphorylation-dependent Alteration in Myofilament Ca2 + Sensitivity but Normal Mitochondrial Function in Septic Heart
Population
Skinned fibers isolated from rabbit ventricle in a nonlethal but hypotensive model of endotoxemia
Comparison
Lipopolysaccharide injection to induce endotoxemia vs Control animals/fibers
Design
Preclinical
Follow-up
36 hours
Authors
Discussion
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Implication
May underlie myocardial depression in sepsis; hypothesis-generating for human translation and therapeutic targets.
Key Points
- To determine whether septic myocardial depression is caused by impaired mitochondrial energetics or altered myofibrillar calcium sensitivity.
- Assessed skinned ventricular fibers isolated from rabbits 36 hours after lipopolysaccharide (LPS)-induced endotoxemia alongside healthy controls.
- Measured mitochondrial respiration, oxidative phosphorylation coupling, creatine kinase activity, and isometric calcium-activated force.
- Treated fibers with protein kinase A (PKA), alkaline phosphatase, isoproterenol, or the nitric oxide donor SNAP to assess regulatory phosphorylation mechanisms.
- Half-maximal calcium sensitivity (pCa50) was significantly decreased in LPS fibers (5.55 ± 0.01, n = 11) compared to control fibers (5.61 ± 0.01, n = 10; p < 0.01), while maximal calcium-activated force remained unaltered.
- Mitochondrial respiration, coupling between oxidation and phosphorylation, and creatine kinase activity showed no significant differences between LPS and control groups.
- PKA and alkaline phosphatase abolished the difference in pCa50 between groups, while isoproterenol decreased control pCa50 from 5.62 ± 0.01 to 5.55 ± 0.01 (p < 0.01).
Structured PICO
P
Population
Skinned fibers isolated from rabbit ventricle in a nonlethal but hypotensive model of endotoxemia
I
Intervention
Lipopolysaccharide (LPS) injection to induce endotoxemia
C
Comparator
Control animals/fibers
O
Outcome
Myofibrillar Ca2+ sensitivity (pCa50) and mitochondrial function (respiration, coupling, creatine kinase function)surrogate
During sepsis, cardiac mitochondrial function remains unaltered, but protein phosphorylation decreases myofibrillar Ca2+ sensitivity, which may contribute to myocardial depression.
Cite This Study
Tavernier et al. (2001) studied this question.