Myocyte electrophysiological properties following the development of supraventricular tachycardia-induced cardiomyopathy

Chronic supraventricular tachycardia (SVT) causes left ventricular (LV) dilatation and dysfunction, diminished myocyte contractile function, and abnormalities in sarcolemmal receptor systems. We hypothesized that changes in myocyte action potential characteristics and l-type Ca2+ channel (Ca2+ channel) function, which are major determinants of myocyte contractile processes, would occur with SVT cardiomyopathy. LV function and isolated myocyte contractile function were examined in 11 pigs with SVT cardiomyopathy (pace 240 bpm; 3 weeks) and 11 control pigs. With chronic SVT. LV fractional shortening fell and myocyte shortening velocity was reduced compared to controls (11 ± 2 v 37 ± 2%. P<0.0001; and 32.5 ± 1.2 v 55.7 ± 1.6 μm/s. P<0.0001, respectively). Isolated myocyte action potential upstroke velocity and amplitude were reduced with SVT cardiomyopathy compared to controls (92.8 ± 4.8 v 129.5 ± 3.1 V/s, P<0.0001; and 98.2 ± 2.2 v 110.3 ± 1.3 mV, P<0.0001, respectively). The duration of the myocyte action potential, defined as the time to 90% repolarization, was prolonged with SVT cardiomyopathy compared to controls (201.7 ± 5.9 v 169.1 ± 6.8 ms, P=0.002). These specific abnormalities in the indices of myocyte contractile function and action potential characteristics which occurred with SVT cardiomyopathy were not normalized following β-adrenergic receptor stimulation. In order to determine a potential mechanism for the changes in myocyte contractile function and action potential characteristics with SVT cardiomyopathy, Ca2+ channel function was examined in control and SVT myocytes. In SVT myocytes, peak l-type Ca2+ current (ICa) normalized to membrane capacitance and the Ca2+ channel inactivation time constant were reduced compared to controls (−2.30 ± 0.24 v −3.79 ± 0.28 pA/pF, P = 0.0001; and 104.0 ± 10.8 v 199.9 ± 27.4 ms, P = 0.005, respectively). The abnormalities in Ca2+ channel function with SVT cardiomyopathy persisted in myocytes with equivalent membrane capacitances and were not normalized with β-adrenergic receptor stimulation. In conclusion, findings from the present study suggest that fundamental abnormalities in myocyte electrical events (action potential) and ionic flux (Ca2+ channel function) are contributory mechanisms for the depressed myocyte contractile function with SVT cardiomyopathy.