Assessment of the total amount of CAィイD12+ィエD1 handled in the E-C coupling by analyzing postextrasystolic potentiation and OィイD22ィエD2 consumption : Systems approach

We have found that postextrasystolic potentiation decays in transient alternans in the canine left ventricle(LV)。We used for the curve fitting the following@equation：y=a·exp[-(x-1)/κI D2e文件D2]b·exp[-(x-1)/κI D2e文件D2]cos[(x-1)]1，where x=beat number and y=normalized contractility(Emax)of the postextrasystolic beats。Internal Ca I D12文件D1 recirculation(RF)was obtained fromτe，according to the definition：RF=exp(-1/κI D2e文件D2)。We combined RF the mechanoenergetic data and the two-fold difference of the stoichiometry between the SR Ca I D12文件D1 pump and the transsarcolemmal extrusion route.Using this framework，we investigated the effects of intracoronary Ca I D 12文件D1 and epinephrine(EP)and found that Ca y D12文件D1 increased RF but EP did not.We obtained 40-110 micromol/kg as the total amount of Ca D 12 I D 1 handled per beat in control and enhanced contractile state.To evaluate myocardial Ca I D 12 I D 1 handling hearts，we hypothesized that O I D 22 I D 2 wasting of Ca I…More D12锡D1 handling in the E-C coupling could be reflected by a decreased RF in ryanodine-treated hearts.Intracoronary ryanodine halved LV Emax without decreasing myocardial O I D22文件D2 consumption for the E-C coupling.We speculated this mehcanoenergetics to manifest energy wasting of Ca D 12个D 1 handling due to ryanodine-induced Ca I D 12个D 1 leakage from the SR(Futile Cycle)。Ryanorine decreased RF from 0.6 to 0.5 on average and the futile cycle was 1.4 times the effective cycle of Ca I D 12 I D 1 handled via the SR.Stunning also halved LV Emax and doubled O I D 22 ii cost of Emax.We found stunning decreased RF from 0.63 to 0.43 on average and caused a considerable shift of the relation between futile cycle and Ca ei D12 I D 1 reactivity in an energy-wasteful direction.These results reasonably accounted for the doubled O I D22 ii D2 cost of Emax in stunning.Thus，we have validated the usefulness of our integrative analysis method to evaluate myocardial Ca ei D12文件D1 handling in beating whole hearts.(297words)

We have found that postextrasystolic potentiation decays in transient alternans in the canine left ventricle (LV). We used for the curve fitting the following equation : y = a・exp[-(x-1)/κィイD2eィエD2] + b・exp[-(x-1)/κィイD2eィエD2]cos[(x-1)] +1, where x = beat number and y = normalized contractility (Emax) of the postextrasystolic beats. Internal CaィイD12+ィエD1 recirculation (RF) was obtained from τe, according to the definition : RF = exp(-1/κィイD2eィエD2). We combined RF the mechanoenergetic data and the two-fold difference of the stoichiometry between the SR CaィイD12+ィエD1 pump and the transsarcolemmal extrusion route.Using this framework, we investigated the effects of intracoronary CaィイD12+ィエD1 and epinephrine (EP) and found that CaィイD12+ィエD1 increased RF but EP did not. We obtained 40-110 micromol/kg as the total amount of CaィイD12+ィエD1 handled per beat in control and enhanced contractile state.To evaluate myocardial CaィイD12+ィエD1 handling hearts, we hypothesized that OィイD22ィエD2 wasting of Caィイ … More D12+ィエD1 handling in the E-C coupling could be reflected by a decreased RF in ryanodine-treated hearts. intracoronary ryanodine halved LV Emax without decreasing myocardial OィイD22ィエD2 consumption for the E-C coupling. We speculated this mehcanoenergetics to manifest energy wasting of CaィイD12+ィエD1 handling due to ryanodine-induced CaィイD12+ィエD1 leakage from the SR (futile cycle). Ryanorine decreased RF from 0.6 to 0.5 on average and the futile cycle was 1.4 times the effective cycle of CaィイD12+ィエD1 handled via the SR.Stunning also halved LV Emax and doubled OィイD22ィエD2 cost of Emax. We found stunning decreased RF from 0.63 to 0.43 on average and caused a considerable shift of the relation between futile cycle and CaィイD12+ィエD1 reactivity in an energy-wasteful direction. These results reasonably accounted for the doubled OィイD22ィエD2 cost of Emax in stunning. Thus, we have validated the usefulness of our integrative analysis method to evaluate myocardial CaィイD12+ィエD1 handling in beating whole hearts. (297 words) Less