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To study the calcium-dependent mechanisms contributing to altered contractile function in isoproterenol-induced ventricular hypertrophy of the rat heart.The force-interval relationship, systemic evaluation of changed contractile force and calcium sensitivity of the myofilaments were investigated using small trabecular muscle from hearts with isoproterenol-induced cardiac hypertrophy.Cardiac hypertrophy was induced by daily subcutaneous injection of isoproterenol for 12 days. The calcium sensitivity of myofilaments was studied using nonionic detergent (Triton-X-100)-skinned trabeculae. The contractile force was evaluated at various concentrations of extracellular calcium and muscle lengths. The force-interval relationship was used to reflect altered intracellular calcium handling.The isoproterenol-induced cardiac hypertrophy was associated with significantly enhanced contractile force at various concentrations of extracellular calcium and muscle lengths. Also, an amplified force-interval relationship in hypertrophied muscle at long rest intervals was found. However, this study revealed no change in calcium sensitivity of myofilaments.Altered intracellullar calcium handling contributes to enhanced contractile force in isoproterenol-induced cardiac hypertrophy.