We analyzed total Ca handling of the left ventricle (LV) in the mildly failing heart preparation induced by a temporary intracoronary Ca overloading intervention in eight excised and cross-circulated canine hearts. This Ca intervention consisted of interruption of coronary blood perfusion by Ca-free oxygenated Tyrode perfusion for 10 min followed by high-Ca (16mmol/l) oxygenated Tyrode perfusion for 5 min. This intervention decreased the LV contractility index, Emax (end-systolic maximum elastance), by 40% after restoration of the blood cross-circulation. We expected a Ca overload or paradox failing heart resembling the postischemic stunned heart and being characterized by an increased O2 cost of Emax. However, LV O2 consumption under mechanically unloading conditions decreased by 30% from control without increasing the O2 cost of Emax. To obtain a mechanistic view of this failing heart, we investigated cardiac total Ca handling by our integrative analysis method. In this method, we obtained the internal Ca recirculation fraction (RF) from the decay beat constant of the postextrasystolic potentiation following each sporadic spontaneous extrasystole in these failing LVs. We combined the RF with the decreased Emax and the unchanged O2 cost of Emax in our recently developed formula of total Ca handling. We found that these failing LVs had a slightly but significantly increased RF accompanied by either a slightly increased futile Ca cycling or a slightly decreased Ca reactivity of Emax, or both. Any of these three possible changes can account for the unchanged O2 cost of Emax. This result indicates that the present mildly failing heart has not yet fallen into a typical Ca overload or paradox by the temporary Ca overloading intervention.

Postischemic myocardial stunning halved left ventricular contractility [end-systolic maximum elastance (E(max))] and doubled the O(2) cost of E(max) in excised cross-circulated canine heart. We hypothesized that this increased O(2) cost derived from energy-wasteful myocardial Ca(2+) handling consisting of a decreased internal Ca(2+) recirculation, some futile Ca(2+) cycling, and a depressed Ca(2+) reactivity of E(max). We first calculated the internal Ca(2+) recirculation fraction (RF) from the exponential decay component of postextrasystolic potentiation. Stunning significantly accelerated the decay and decreased RF from 0.63 to 0. 43 on average. We then combined the decreased RF with the halved E(max) and its doubled O(2) cost and analyzed total Ca(2+) handling using our recently developed integrative method. We found a decreased total Ca(2+) transport and a considerable shift of the relation between futile Ca(2+) cycling and Ca(2+) reactivity in an energy-wasteful direction in the stunned heart. These changes in total Ca(2+) handling reasonably account for the doubled O(2) cost of E(max) in stunning, supporting the hypothesis.

No abstract