Key Points
- To determine how acute normothermic global ischemia and acidosis alter cardiac sarcoplasmic reticulum function and excitation-contraction coupling.
- Examined canine myocardial tissue subjected to 7.5, 15, and 30 minutes of normothermic global ischemia.
- Assayed calcium uptake, calcium-ATPase activity, and passive membrane permeability in whole heart homogenates and isolated sarcoplasmic reticulum at pH 7.1 and acidic pH 6.4.
- Whole heart homogenate sarcoplasmic reticulum showed a 49% depression of oxalate-supported calcium uptake at 7.5 minutes of ischemia, deteriorating to an 85% depression at 30 minutes at pH 7.1, with parallel depressions in isolated sarcoplasmic reticulum.
- Acidosis (pH 6.4) right-shifted the pCalcium-ATPase activation curve from pCalcium 6.0 to 5.5 and reduced maximum velocity from 2.06 ± 0.14 to 1.41 ± 0.05 μmol Pi/mg per min (P < 0.01), accompanied by reduced calcium-to-ATP coupling ratios at 15 and 30 minutes.
- Steady-state calcium uptake in the absence of oxalate was significantly depressed after 7.5 and 15 minutes of ischemia across both pH levels, driven by an increased passive calcium permeability coefficient.
Structured PICO
PPopulationCanine model of normothermic global ischemia
IIntervention7.5, 15, and 30 minutes of normothermic global ischemia at pH 7.1 and 6.4
CComparatorControl (non-ischemic) homogenate
OOutcomeSarcoplasmic reticulum function (oxalate-supported calcium uptake and calcium-ATPase activity)surrogate
Short-term global ischemia and acidosis progressively depress sarcoplasmic reticulum calcium uptake and calcium-ATPase activity in a canine model, contributing to myocardial dysfunction.