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Cellular versus myocardial basis for the contractile dysfunction of hypertrophied myocardium
1Department of Medicine, Gazes Cardiac Research Institute, Medical University of South Carolina, Charleston.
Insights
Contractile dysfunction in pressure-overloaded right ventricles is intrinsic to cardiac muscle cells. This study demonstrates that hypertrophied cardiocytes exhibit significant systolic and relengthening abnormalities, not due to the surrounding environment.
Area of Science:
- Cardiology
- Cell Biology
- Physiology
Background:
- Right ventricular pressure-overload hypertrophy is associated with contractile dysfunction.
- The origin of this dysfunction (intrinsic to cardiac muscle cells or the interstitial environment) remains unclear.
Purpose of the Study:
- To investigate the intrinsic contractile behavior of cardiac muscle cells (cardiocytes) in a model of right ventricular pressure-overload hypertrophy.
- To differentiate between cell-intrinsic and environmental contributions to contractile dysfunction.
Main Methods:
- Isolated right ventricular cardiocytes from pressure-overloaded and control cats were subjected to contractile function analysis.
- Laser diffraction was used to measure sarcomere shortening and relengthening under controlled conditions.
Main Results:
- Hypertrophied cardiocytes exhibited significantly reduced peak shortening velocity and extent.
- Time to peak shortening and relengthening were prolonged in hypertrophied cardiocytes.
- Peak rate of sarcomere relengthening was significantly decreased in hypertrophied cells.
Conclusions:
- The contractile defect in experimental right ventricular pressure-overload hypertrophy is intrinsic to the cardiac muscle cell.
- This finding shifts focus towards understanding the cellular mechanisms underlying this dysfunction.
Abstract:
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.