title: Evaluation of left ventricular mechanical work and energetics of normal hearts in SERCA2a transgenic rats.
abstract: Cardiac sarcoplasmic reticulum (SR) Ca(2+)-ATPase (SERCA2a) is responsible for most of the Ca(2+) removal during diastole and a larger Ca(2+) handling energy consumer in excitation-contraction (E-C) coupling. To understand the cardiac performance under long-term SERCA2a overexpression conditions, we established SERCA2a transgenic (TG) Wistar rats to analyze cardiac mechanical work and energetics in normal hearts during pacing at 300 beats/min. SERCA2a protein expression was increased in TGI and TGII rats (F2 and F3 of the same father and different mothers). Mean left ventricular (LV) end-systolic pressure (ESP) and systolic pressure-volume area (PVA; a total mechanical energy per beat) at midrange LV volume (mLVV) were significantly larger in TGI rats and were unchanged in TGII rats, compared to those in non-TG [wildtype (WT)] littermates. Mean myocardial oxygen consumption per minute for E-C coupling was significantly increased, and the mean slope of myocardial oxygen consumption per beat (VO(2))-PVA (systolic PVA) linear relation was smaller, but the overall O(2) cost of LV contractility for Ca(2+) is unchanged in all TG rats. Mean Ca(2+) concentration exerting maximal ESP(mLVV) in TGII rats was significantly higher than that in WT rats. The Ca(2+) overloading protocol did not elicit mitochondrial swelling in TGII rats. Tolerance to higher Ca(2+) concentrations may support the possibility for enhanced SERCA2a activity in TGII rats. In conclusion, long-term SERCA2a overexpression enhanced or maintained LV mechanics, improved contractile efficiency under higher energy expenditure for Ca(2+) handling, and improved Ca(2+) tolerance, but it did not change the overall O(2) cost of LV contractility for Ca(2+) in normal hearts of TG rats.
authors.affiliation: Department of Physiology II, Nara Medical University School of Medicine, 840 Shijo-cho, Kashihara, Nara 634-8521, Japan.
authors.forename: Guo-Xing
authors.initials: GX
authors.lastname: Zhang
authors.forename: Koji
authors.initials: K
authors.lastname: Obata
authors.forename: Daisuke
authors.initials: D
authors.lastname: Takeshita
authors.forename: Shinichi
authors.initials: S
authors.lastname: Mitsuyama
authors.forename: Tamiji
authors.initials: T
authors.lastname: Nakashima
authors.forename: Akio
authors.initials: A
authors.lastname: Kikuta
authors.forename: Masumi
authors.initials: M
authors.lastname: Hirabayashi
authors.forename: Koichi
authors.initials: K
authors.lastname: Tomita
authors.forename: Roland
authors.initials: R
authors.lastname: Vetter
authors.forename: Wolfgang H
authors.initials: WH
authors.lastname: Dillmann
authors.forename: Miyako
authors.initials: M
authors.lastname: Takaki
mesh_terms: D000818:Animals; D002118:Calcium / Q000494:pharmacology; D056966:Excitation Contraction Coupling / Q000502:physiology; D008297:Male; D010101:Oxygen Consumption / Q000502:physiology; D051381:Rats; D055647:Rats, Transgenic; D017208:Rats, Wistar; D012519:Sarcoplasmic Reticulum / Q000378:metabolism; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000096:biosynthesis / Q000235:genetics*; D016277:Ventricular Function, Left / Q000187:drug effects / Q000502:physiology*
chemical_list: D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D002118:Calcium