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Increased left ventricular diastolic stiffness in the early phase of hereditary cardiomyopathy
V I Kapelko1, W W Parmley, S Wu
1Department of Medicine, University of California, San Francisco.
Insights
Cardiomyopathy in hamsters shows enlarged chambers and increased diastolic stiffness. This stiffness, linked to diastolic volume overload and wall stress, is a key early sign, unlike alcohol-induced cardiac depression.
Area of Science:
- Cardiology
- Biochemistry
- Physiology
Background:
- Cardiomyopathy is a significant cardiac condition affecting heart muscle function.
- Understanding early changes in cardiac mechanics and energetics is crucial for disease management.
Purpose of the Study:
- To investigate the mechanical and energetic properties of isolated hearts from cardiomyopathic hamsters.
- To compare the effects of diastolic volume overload and wall stress in normal versus diseased hearts.
Main Methods:
- Isolated heart perfusion in normal and cardiomyopathic hamsters.
- Echocardiography and 31P-nuclear magnetic resonance (NMR) for cardiac assessment.
- Intraventricular balloon inflation to induce controlled volume overload and stress.
Main Results:
- Cardiomyopathic hamsters exhibited relative left ventricular chamber enlargement and increased diastolic stiffness.
- 31P-NMR revealed decreased phosphocreatine/inorganic phosphate (PCr/Pi) ratios, indicating altered cardiac energetics.
- Increased diastolic stiffness in cardiomyopathic hearts was not replicated by acute alcohol-induced dilatation in control hearts.
Conclusions:
- Diastolic volume overload and increased wall stress are primary contributors to early diastolic stiffness in this model of cardiomyopathy.
- Altered cardiac energetics (reduced PCr/Pi) are associated with the progression of cardiomyopathy.
- The findings differentiate pathological stiffness from acute, reversible cardiac depression.
Abstract:
Isolated hearts from normal and cardiomyopathic hamsters (160 to 180 days of age) were perfused through the aorta and assessed by echocardiographic and 31P-NMR (nuclear magnetic resonance) techniques. A decreased left ventricular systolic pressure in cardiomyopathic hamsters was associated with diminished cardiac size and left ventricular wall thickness. However, the ratio of inner/outer cross-sectional area and estimated left ventricular volume at any given left ventricular weight was significantly higher, indicating relative left ventricular chamber enlargement in cardiomyopathic hamsters. Left ventricular volumes were increased with an intraventricular balloon. Gradual inflation of the balloon resulted in increments of left ventricular systolic and developed stress that rose to the same values in both groups. At this point, the normalized stress-strain relationship was approximately two times steeper for cardiomyopathic hamsters, while at lower strain values the diastolic stress in cardiomyopathic hamsters was less than in controls, possibly due to cardiac dilatation. Almost the same degree of dilatation was induced in control hearts by the acute addition of 1% alcohol, but it was not followed by increased diastolic stiffness. Examination of hearts by 31P-NMR techniques revealed a decreased phosphocreatine/inorganic phosphate (PCr/Pi) ratio in the cardiomyopathic hamsters that progressed further with balloon inflation and was associated with a relative fall in PCr and adenosine triphosphate (ATP) content. Results suggest increased diastolic stiffness in cardiomyopathic hamsters, which was not seen in acute cardiac depression with alcohol. Diastolic volume overload with increased wall stress is probably the major factor contributing to increased diastolic stiffness early in the cardiomyopathy.