Macro-micro correspondence in mechanoenagetics of failing hearts

We have developed an organ-level systems approach to quantify total Ca I D12+台D1 handling in normal hearts.However，its direct application to failing hearts，where futile Ca I D12+I D1 cycling via the Ca I D 12+ii D1-leaky sarcoplasmic reticulum(SR)required an increased Ca I D 12+ii D1 handling Vo I D 22 ii D 2，was not legitimate.To quantify total Ca I D12+I D 1 handling even in such failing hearts，we calculated internal Ca I D 12+I D 1 recirculation fraction(RF)from the exponential decay component of postextrasystolic potentiation(PESP)and combined the RF with the halved left ventricular(LV)contractility(Emax)and its O I D 22 E D2 cost.We applied this new integrative method to three kinds of failing hearts.1.Failing hearts after intracoronary ryanodine at nanomolar concentrations halved Emax without significantly decreasing Ca I D12+I D1 handling Vo I D 22 I D 2.We found that ryanodine significantly decreased RF from 0.6 to 0.5 on the average。We also found that futile Ca I D12+I D1 cycling via…More the SR increased to&gt；1 cycle/beat after ryanodine from presumably zero before ryanodine.2。We analyzed total Ca I D 12+I D 1 handling of the LV in the mildly failing heart preparation induced by a temporary intracoronary Ca Y D 12+I D 1 overloading intervention.This intervention decreased Emax by 40%and Ca I D12+I D 1 handling Vo I D 22 I D 2 by 30%without increasing the O I D 22 I D 2 cost of Emax.We found that these failing hearts had a slightly but significantly increased RF accompanied by either a slightly increased futile Ca I D12+文件D1 cycling or a slightly decreased Ca I D 12+I D 1 reactivity of Emax，or both。Any of these three possible changes can account for the unchanged O I D22 ii D2 cost of Emax.3。Postischemic myocardial stunning halved Emax and doubled O I D22文件D2 cost of Emax。Stunning decreased RF from 0.63 to 0.43 on the average.We found a decreased total Ca I D 12+I D 1 transport and a considerable shift of the relation between futile Ca I D 12+I D 1 cycling and Ca I D 12+I D 1 reactivity in an energy-wasteful direction in the stunned heart.Less：Less

We have developed an organ-level systems approach to quantify total CaィイD12+ィエD1 handling in normal hearts. However, its direct application to failing hearts, where futile CaィイD12+ィエD1 cycling via the CaィイD12+ィエD1-leaky sarcoplasmic reticulum (SR) required an increased CaィイD12+ィエD1 handling VoィイD22ィエD2, was not legitimate. To quantify total CaィイD12+ィエD1 handling even in such failing hearts, we calculated internal CaィイD12+ィエD1 recirculation fraction (RF) from the exponential decay component of postextrasystolic potentiation (PESP) and combined the RF with the halved left ventricular (LV) contractility (Emax) and its OィイD22ィエD2 cost.We applied this new integrative method to three kinds of failing hearts.1. Failing hearts after intracoronary ryanodine at nanomolar concentrations halved Emax without significantly decreasing CaィイD12+ィエD1 handling VoィイD22ィエD2. We found that ryanodine significantly decreased RF from 0.6 to 0.5 on the average. We also found that futile CaィイD12+ィエD1 cycling via … More the SR increased to >1 cycle/beat after ryanodine from presumably zero before ryanodine.2. We analyzed total CaィイD12+ィエD1 handling of the LV in the mildly failing heart preparation induced by a temporary intracoronary CaィイD12+ィエD1 overloading intervention. This intervention decreased Emax by 40% and CaィイD12+ィエD1 handling VoィイD22ィエD2 by 30% without increasing the OィイD22ィエD2 cost of Emax. We found that these failing hearts had a slightly but significantly increased RF accompanied by either a slightly increased futile CaィイD12+ィエD1 cycling or a slightly decreased CaィイD12+ィエD1 reactivity of Emax, or both. Any of these three possible changes can account for the unchanged OィイD22ィエD2 cost of Emax.3. Postischemic myocardial stunning halved Emax and doubled OィイD22ィエD2 cost of Emax. Stunning decreased RF from 0.63 to 0.43 on the average. We found a decreased total CaィイD12+ィエD1 transport and a considerable shift of the relation between futile CaィイD12+ィエD1 cycling and CaィイD12+ィエD1 reactivity in an energy-wasteful direction in the stunned heart. Less