RYANODINE DECREASES INTERNAL CA2+ RECIRCULATION FRACTION OF THE CANINE HEART AS STUDIED BY POSTEXTRASYSTOLIC TRANSIENT ALTERNANS

We tested our hypothesis that the O-2 wasting of Ca2+ handling in the excitation-contraction (E-C) coupling in ryanodine-treated failing hea rts could be reflected by a decrease in the internal Ca2+ recirculatio n fraction (RF). We have reported, using canine excised cross-circulat ed hearts, that intracoronary ryanodine (40 nmol/l blood) halved left ventricular contractility without decreasing myocardial O-2 consumptio n for the E-C coupling. We previously suspected this mechanoenergetic state to manifest energy wasting of Ca2+ handling due to ryanodine cau sing leakage of Ca2+ from the sarcoplasmic reticulum. To test this hyp othesis, we analyzed ail the sporadic spontaneous cases of postextrasy stolic potentiation (PESP) obtained during the ryanodine experiments. We calculated HF from the beat constant of the exponential decay compo nent of not only the monotonic type but also the transient alternans t ype of PESP. Results showed that ryanodine significantly decreased the beat constant in both types of PESP from about 2 to 1.5 beats and hen ce RF from 0.6 to 0.5 on the average, supporting the hypothesis, This organ-level systems approach to Ca2+ handling using transient alternan s PESP as well as monotonic PESP may help obtain better insights into the mechanoenergetics of failing hearts.