The Relationship Between Changes in Myocyte Electrical and Contractile Events with the Development of Dilated Cardiomyopathy

Changes in myocyte (MYO) membrane potential (MYO-MP) are major determinants in contractile processes. We hypothesized that the development of dilated cardiomyopathy (DCM) will cause specific changes in MYO-MPs and be directly associated with well defined abnormalities in MYO contractile events. Simultaneous indices of isolated MYO-MP (resting, RMP; max upstroke velocity, Vmax; time to 90% repolarization, APD90) and contraction (velocities of shortening, VELSHT; and relengthening, VELLEN) were obtained in 7 pigs with DCM (pace 240bpm; 3wks) and 7 control (CON) pigs at baseline (BAS) and with β-AR stimulation (25 nM isoproterenol) using micro-electrodes and high speed videomicroscopy. Baseline MYO-MPs recorded from control and DCM MYO are shown in Figure 1. MYO-MPs at peak MYO contraction and at end of MYO contraction were higher with DCM compared to CON (−48 ± 4* vs − 65 ± 3 mV; and −71 ± 1* vs −78 ± 1 mV). Thus, more positive MYO-MPs were observed; particularly during active MYO relaxation. The abnormalities in the MYO-MP and MYO contractile relationships were not normalized with β-AR stimulation. Summary: In this model of dilated cardiomyopathy, significant alterations in myocyte contractile function and action potential characteristics were observed. These alterations in the temporal relationship between myocyte electrical and mechanical events may be fundamental contributory mechanism responsible for the contractile dysfunction observed in this model of cardiomyopathic disease.