title: Sarcoplasmic reticulum Ca2+ loading in rabbits 8 and 15 weeks after coronary artery ligation.
abstract: Calcium uptake by cardiac sarcoplasmic reticulum (SR) is reported to be reduced in heart failure in the human and in a number of animal models. However, the majority of studies have examined end-stage heart failure in the human and few animal studies have taken account of the duration and severity of left ventricular dysfunction. In this study we have compared SR Ca2+ loading in a haemodynamically assessed, coronary artery ligation model of heart failure at 8 and 15 weeks after ligation. Trabeculae were isolated from the right ventricle and mounted for isometric tension measurement. They were treated with saponin to permeabilize the sarcolemma but retain SR function and bathed in a mock intracellular solution including adenosine triphosphate (ATP) and buffered Ca2+. Caffeine was used to release Ca2+ from the SR. The amplitude of the caffeine-induced contracture was used as a quantitative gauge of the Ca2+ content of the SR. Eight weeks after ligation, trabeculae demonstrated enhanced SR Ca2+ uptake as manifest by larger caffeine-induced contractures (e.g. 200 nM [Ca2+], 120 s loading - 38.2+/-9.2 versus 67.3+/-10.1% of maximum Ca2+-activated force, FCa, max, P=0.03). At 15 weeks, trabeculae from ligated hearts were not significantly different from controls with SR Ca2+ loading returning to control levels (e.g. 200 nM [Ca2+], 120 s loading - 47.3+/-9.6 versus 30.2+/-12.8% FCa, max, P=0.12). These data suggest that SR Ca2+ loading may increase in the early stages of heart failure and fall back to normal with an increasing duration of left ventricular dysfunction. Increased incidence of spontaneous Ca2+ release observed from the SR at 8 weeks and not at 15 weeks may represent an arrhythmogenic mechanism specific to the early phase of heart failure.
authors.affiliation: Department of Medical Cardiology, Glasgow Royal Infirmary, 10 Alexandra Parade, Glasgow G31 2ER, UK.
authors.forename: M A
authors.initials: MA
authors.lastname: Denvir
authors.forename: N G
authors.initials: NG
authors.lastname: MacFarlane
authors.forename: S M
authors.initials: SM
authors.lastname: Cobbe
authors.forename: D J
authors.initials: DJ
authors.lastname: Miller
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002303:Cardiac Output, Low / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology; D003327:Coronary Disease / Q000150:complications / Q000378:metabolism* / Q000503:physiopathology; D006439:Hemodynamics; D007537:Isometric Contraction; D008026:Ligation; D009206:Myocardium / Q000378:metabolism*; D011817:Rabbits; D012503:Saponins / Q000494:pharmacology; D012519:Sarcoplasmic Reticulum / Q000378:metabolism*; D013997:Time Factors; D018487:Ventricular Dysfunction, Left / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology
chemical_list: D012503:Saponins; D002118:Calcium