Cellular versus myocardial basis for the contractile dysfunction of hypertrophied myocardium.

Contractile dysfunction has been demonstrated in many previous studies of experimental right ventricular pressure-overload hypertrophy; however, given the complex changes that occur both in the cardiac muscle cell and in the multiple components of the cardiac interstitium, it is not clear whether the contractile dysfunction observed is an intrinsic property of the cardiac muscle cell or whether it is the result of a mechanically normal cardiac muscle cell contracting within an abnormal interstitial environment. The purpose of the present study was to examine the contractile behavior of cardiac muscle cells, or cardiocytes, isolated from seven cat right ventricles that were pressure-overloaded by banding the pulmonary artery; right ventricular cardiocytes from seven sham-operated cats served as controls. Cardiocytes were obtained from these cats via standard cell isolation procedures; contractile function of the cardiocytes in response to graded viscous external loads was defined by laser diffraction. The cells were stimulated to contract at a frequency of 0.25 Hz, using 100-microA direct current pulses of alternating polarity. Hypertrophied right ventricular cardiocytes obtained from banded cats showed marked systolic contractile abnormalities in comparison with right ventricular cardiocytes from sham-operated cats. The peak velocity of sarcomere shortening for the control and hypertrophied cardiocytes in 1-cp superfusate was 3.6 +/- 0.2 and 2.1 +/- 0.1 microns/sec, respectively (p less than 0.001); the maximum extent of sarcomere shortening for the control and hypertrophied cardiocytes was 0.21 +/- 0.01 and 0.14 +/- 0.01 microns, respectively (p less than 0.001). Further, the time to peak shortening in the 1-cp superfusate was significantly longer for the hypertrophied cardiocytes (150.1 +/- 3.3 versus 160.4 +/- 3.7 msec; p less than 0.04). When the relengthening properties of the cells were examined in the 1-cp superfusate, there were significant differences between cardiocyte groups. The peak rate of sarcomere relengthening was 3.5 +/- 0.2 microns/sec in the control cardiocytes and 2.2 +/- 0.17 microns/sec in the hypertrophied cardiocytes (p less than 0.001). Similarly, the time to peak velocity of sarcomere relengthening (48.8 +/- 1.8 versus 57.9 +/- 2.9 msec) and the time to 50% maximal sarcomere relengthening (57.1 +/- 3.1 versus 67.1 +/- 3.1 msec) were both significantly prolonged for the hypertrophied cardiocytes (p less than 0.02). This study shows for the first time that the contractile defect in this model of right ventricular pressure-overload hypertrophy is intrinsic to the cardiac muscle cell itself. This finding provides a basis for further, more focused investigations designed to determine the mechanisms responsible for the contractile dysfunction observed in this form of experimental cardiac hypertrophy.