SARCOPLASMIC-RETICULUM CA2-ARTERY LIGATION( LOADING IN RABBITS 8 AND 15 WEEKS AFTER CORONARY)

Calcium uptake by cardiac sarcoplasmic reticulum (SR) is reported to b e reduced in heart failure in the human and in a number of animal mode ls. However. the majority of studies have examined end-stage heart fai lure in the human and few animal studies have taken account of the dur ation and severity of left ventricular dysfunction. In this study we h ave compared SR Ca2+ lending in a haemodynamically assessed, coronary artery ligation model of heart failure at 8 and 15 weeks after ligatio n. Trabeculae were isolated from the right ventricle and mounted for i sometric tension measurement. They were treated with saponin to permea bilize the sarcolemma but retain SR function and bathed in a mock intr acellular 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 dem onstrated enhanced SR Ca2+ uptake as manifest by larger caffeine-induc ed contractures (e.g. 200 nM [Ca2+]. 120 s loading - 38.2+/-9.2 versus 67.3+/-10.1% of maximum Ca2+-activated force, F-Ca,F- max, P=0.03). A t 15 weeks, trabeculae from ligated hearts were not significantly diff er-ent 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% F- Ca,F- max, P=0.12). These data suggest that SR Ca'S loading may increa se in the early stages of heart failure and fall back to normal with a n increasing duration of left ventricular dysfunction. Increased incid ence of spontaneous Ca2+ release observed from the SR at 8 weeks and n ot at 15 weeks may represent an arrhythmogenic mechanism specific to t he early phase of heart failure.