title: A new integrative method to quantify total Ca2+ handling and futile Ca2+ cycling in failing hearts.
abstract: Ca2+ handling in excitation-contraction coupling requires considerable O2 consumption (VO2) in cardiac contraction. We have developed an integrative method to quantify total Ca2+ handling in normal hearts. However, its direct application to failing hearts, where futile Ca2+ cycling via the Ca2+-leaky sarcoplasmic reticulum (SR) required an increased Ca2+ handling VO2, was not legitimate. To quantify total Ca2+ handling even in such failing hearts, we combined futile Ca2+ cycling with Ca2+ handling VO2 and the internal Ca2+ recirculation fraction via the SR. We applied this method to the canine heart mechanoenergetics before and after intracoronary ryanodine at nanomolar concentrations. We found that total Ca2+ handling per beat was halved after the ryanodine treatment from approximately 60 micromol/kg left ventricle before ryanodine. We also found that futile Ca2+ cycling via the SR increased to >1 cycle/beat after ryanodine from presumably zero before ryanodine. These results support the applicability of the present method to the failing hearts with futile Ca2+ cycling via the SR.
authors.affiliation: Department of Physiology II, Okayama University Medical School, Okayama 700-8558, 634-8521 Japan.
authors.forename: J
authors.initials: J
authors.lastname: Shimizu
authors.forename: J
authors.initials: J
authors.lastname: Araki
authors.forename: J
authors.initials: J
authors.lastname: Mizuno
authors.forename: S
authors.initials: S
authors.lastname: Lee
authors.forename: Y
authors.initials: Y
authors.lastname: Syuu
authors.forename: S
authors.initials: S
authors.lastname: Hosogi
authors.forename: S
authors.initials: S
authors.lastname: Mohri
authors.forename: T
authors.initials: T
authors.lastname: Mikane
authors.forename: M
authors.initials: M
authors.lastname: Takaki
authors.forename: T W
authors.initials: TW
authors.lastname: Taylor
authors.forename: H
authors.initials: H
authors.lastname: Suga
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D000252:Calcium-Transporting ATPases / Q000378:metabolism; D002303:Cardiac Output, Low / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology; D002309:Cardiology / Q000379:methods; D004285:Dogs; D004734:Energy Metabolism / Q000502:physiology; D005240:Feasibility Studies; D006321:Heart / Q000187:drug effects / Q000503:physiopathology; D066298:In Vitro Techniques; D008955:Models, Cardiovascular; D009200:Myocardial Contraction / Q000502:physiology; D009206:Myocardium / Q000378:metabolism*; D010101:Oxygen Consumption / Q000502:physiology; D012433:Ryanodine / Q000494:pharmacology; D012519:Sarcoplasmic Reticulum / Q000378:metabolism
chemical_list: D012433:Ryanodine; D000252:Calcium-Transporting ATPases; D002118:Calcium