Effect of preconditioning on ryanodine-sensitive Ca²⁺ release from sarcoplasmic reticulum of rat heart

The effect of varying the number of preconditioning (PC) episodes on the recovery of cardiac function and on the function of the sarcoplasmic reticulum (SR) was investigated to determine the correlation between the effect of PC and SR function. Isolated rat hearts were subjected to zero to three 5-min episodes of global ischemia with intermittent perfusion (PC₀- PC₃) followed by 25 min of ischemia (I) and 30 min of reperfusion. The left ventricular (LV) pressure and SR ⁴⁵Ca²⁺ uptake in the absence or presence of ryanodine were then measured. The increase in LV end-diastolic pressure and the incidence and duration of ventricular tachyarrhythmias during reperfusion decreased. The recovery of LV developed pressure, LV dP/dt(max) and dP/dt(min), increased as the number of episodes of PC increased. The rates of SR ⁴⁵Ca²⁺ uptake after PC and after reperfusion were lower in PC₃ than in PC₀. Conversely, the rate of ⁴⁵Ca²⁺ uptake after I did not differ between PC₀ and PC₃. The ryanodine-sensitive Ca²⁺ release increased after I, and additional increases were observed during reperfusion in PC₀, whereas the release after I and reperfusion decreased progressively in PC₃. These observations show that the beneficial effects of PC are associated with a decrease in ryanodine-sensitive SR Ca²⁺ release.