ENHANCED SR FUNCTION IN SAPONIN-TREATED VENTRICULAR TRABECULAE FROM RABBITS WITH HEART-FAILURE

Cardiac sarcoplasmic reticulum (SR) Ca2+-loading ability was assessed in a coronary artery ligation model of heart failure. Heart failure wa s produced in New Zealand White rabbits by ligation of the left margin al coronary artery. Sham-operated animals were used as controls. After hemodynamic and echocardiographic assessment 8 wk after coronary liga tion, a free-running trabecula was isolated from the left or right ven tricle, mounted for isometric tension measurement, and permeabilized w ith the chemical skinning agent saponin, leaving the SR functionally i ntact. The SR was Ca2+ loaded by exposure of the preparation to a mock intracellular solution with a Ca2+ concentration ([Ca2+]) of 150-300 nM. The amplitude of the caffeine-induced contracture was used as a me asure of Ca2+ loaded by the SR. The same preparation was then treated with Triton X-100 to disrupt all cell membranes, and Ca2+ sensitivity {expressed as [Ca2+] required to produce 50% of maximal activation (pC a(50))} of isometric tension production and maximum Ca2+ activated for ce (C-max) were measured. Ligated animals demonstrated enhanced SR Ca2 +-loading ability that correlated with the degree of left ventricular dysfunction. Enhanced SR Ca2+ loading was associated with evidence of SR Ca2+ overload revealed as spontaneous tension oscillations. C-max a nd pCa(50) were not significantly different from controls. Increased S R Ca2+-loading ability may predispose the SR to Ca2+ overload and coul d contribute to both contractile dysfunction and arrhythmogenesis in h eart failure.