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Total Ca handling in canine mild Ca overload failing heart

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Summary

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 10min followed by high-Ca (16 mmol/l) oxygenated Tyrode perfusion for 5 min. This intervention decreased the LV contractility index,E max (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 ofE max. However, LV O2 consumption under mechanically unloading conditions decreased by 30% from control without increasing the O2 cost ofE max. 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 decreasedE max and the unchanged O2 cost ofE max 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 ofE max, or both. Any of these three possible changes can account for the unchanged O2 cost ofE max. 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.

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This study was partly supported by Grants-in-Aid for Scientific Research (09470009, 10770307, 10558136, 10877006) from the Ministry of Education, Science, Sports and Culture, a 1998 Frontier Research Grant for Cardiovascular System Dynamics from the Science and Technology Agency, all of Japan.

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Mizuno, J., Araki, J., Iribe, G. et al. Total Ca handling in canine mild Ca overload failing heart. Heart Vessels 14, 38–51 (1999). https://doi.org/10.1007/BF02481741

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