Relationship between external load and isolated myocyte contractile function with CHF in pigs

Past studies have demonstrated that the negative relationship between afterload and contractile performance of papillary muscles is shifted downward and to the left with the development of hypertrophy. However, it remained unclear whether a similar load-contractility relationship could be constructed for isolated myocytes, particularly with the development of congestive heart failure (CHF). Accordingly, the effect of incrementally increased external loads on the contractile performance of left ventricular (LV) myocytes isolated from pigs in the normal state (n = 5) and after the development of chronic supraventricular tachycardia (SVT)-induced CHF (SVT-CHF; 240 beats/min, 3 wk; n = 5) was examined. This study used precalibrated microspheres to impose a quantifiable load on isolated myocytes, and myocyte contractility was assessed by videomicroscopy. Steady-state unloaded extent of'shortening was 5.4 ± 0.2 μm in control myocytes (n = 80) and was significantly reduced in the myocytes with the development of SVT-CHF (4.4 ± 0.2 μm, n = 93; P < 0.05). Inverse relationships between relative resistive load and myocyte contractile function were observed at both normal and CHF states (r2 > 0.85). For myocyte velocity of shortening, the slope of this relationship was significantly reduced in the SVT-CHF state compared with controls (-46.3 x 10-6 and -34.6 x 10-6 μm3 μN-1.s-1, respectively; P < 0.05). At higher relative resistive loads (>0.18 x 10-6 μN/μm2), the reduction in myocyte shortening extent under an equivalent relative resistive load was significantly greater in the SVT-CHF myocytes compared with controls (62.8 ± 3.9 vs. 45.6 ± 4.7%, respectively, P < 0.05). The present study demonstrated for the first time that a load-dependent relationship can be derived for intact isolated LV myocytes in both normal and CHF states. The defect in the capacity of SVT-CHF myocytes to respond to an increased relative resistive load is a likely contributory mechanism for the LV pump dysfunction that occurs in this model of CHF.