Key Points
- To investigate how acute pharmacological inhibition of creatine kinase affects skeletal muscle oxygen uptake kinetics and high-energy phosphate metabolism during transitions from rest to exercise.
- In situ isolated canine gastrocnemius muscles (n=6) were evaluated across 3-minute electrically stimulated contractions eliciting ~70% peak oxygen uptake.
- Muscles received a 10-minute arterial infusion of either saline control or 5 mM iodoacetamide to inhibit creatine kinase during pump-perfused constant elevated blood flow.
- Oxygen uptake was determined at rest and every 5–7 seconds using Fick's principle alongside continuous muscle force recording and freeze-clamped biopsy analysis.
- Creatine kinase inhibition produced severe early fatigue (fatigue index: 0.67 ± 0.07 in iodoacetamide vs. 1.01 ± 0.03 in control) and reduced end-contraction oxygen uptake (4.2 ± 1.3 vs. 15.3 ± 1.8 ml/100g/min).
- Phosphocreatine breakdown was suppressed in iodoacetamide (Δ[PCr] = 6.5 ± 4.3 vs. 30.8 ± 3.6 mmol/kg DM in control), accompanied by greater ATP depletion (Δ[ATP] = 8.3 ± 3.9 vs. 2.7 ± 0.7 mmol/kg DM).
- Following a comparable time delay (9.4 ± 3.1 s vs. 6.6 ± 1.1 s), the time constant of oxygen uptake kinetics was significantly faster in iodoacetamide (9.5 ± 2.7 s) than control (16.6 ± 1.1 s).
Structured PICO
PPopulationIsolated canine gastrocnemius muscles in situ (n=6)
IIntervention10 min arterial infusion of 5 mM iodoacetamide (IA) to inhibit creatine kinase, along with a vasodilatory drug
CComparator10 min arterial infusion of saline control (CTRL), along with a vasodilatory drug
OOutcomeTime constant of VO2 kinetics during transitions from rest to 3-min of electrically-stimulated contractionssurrogate
Inhibition of creatine kinase accelerates skeletal muscle oxygen uptake kinetics, indicating that normal temporal energy buffering via CK slows the signal transduction to oxidative phosphorylation at the onset of contractions.