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Calcium uptake by cardiac sarcoplasmic reticulum in human dilated cardiomyopathy
C J Limas1, M T Olivari, I F Goldenberg
1Department of Medicine, University of Minnesota School of Medicine, Minneapolis 55455.
Insights
Dilated cardiomyopathy in humans shows impaired sarcoplasmic reticulum function, leading to reduced calcium uptake. This dysfunction is linked to heart failure severity and increased sympathetic nervous system activity.
Area of Science:
- Cardiology
- Biochemistry
- Molecular Biology
Background:
- Human dilated cardiomyopathy is characterized by abnormal diastolic properties.
- The underlying biochemical mechanisms, particularly sarcoplasmic reticulum (SR) function, require elucidation.
Purpose of the Study:
- To investigate the biochemical basis of impaired diastolic function in dilated cardiomyopathy.
- To assess sarcoplasmic reticulum calcium uptake in human ventricular tissue.
Main Methods:
- Ventricular homogenates from 21 dilated cardiomyopathy patients and 9 controls were analyzed.
- Sarcoplasmic reticulum calcium uptake rates were measured and compared between groups.
Main Results:
- Patients with dilated cardiomyopathy exhibited significantly lower SR calcium uptake rates (3.3 nmol.mg-1.min-1) compared to normal controls (6.5 nmol.mg-1.min-1).
- Calcium uptake rates correlated with hemodynamic parameters and plasma noradrenaline levels, but not plasma renin activity.
Conclusions:
- Sarcoplasmic reticulum function is demonstrably impaired in human dilated cardiomyopathy.
- This impairment is associated with the severity of hemodynamic dysfunction and sympathetic nervous system activation.
Abstract:
To determine the biochemical basis of abnormal diastolic properties in human dilated cardiomyopathy calcium uptake by the sarcoplasmic reticulum in ventricular homogenates of biopsy specimens from 21 patients with dilated cardiomyopathy was compared with that in nine normal controls. As a group, patients with cardiomyopathy had considerably lower calcium uptake rates (3.3(0.6) nmol.mg-1.min-1 vs 6.5(0.5) nmol.mg-1.min-1, p less than 0.01). Calcium uptake rates correlated modestly with resting haemodynamic values and significantly with plasma noradrenaline concentrations but not with plasma renin activity. These results show that sarcoplasmic reticulum function is impaired in human dilated cardiomyopathy and that this impairment is related both to the severity of haemodynamic dysfunction and to the extent of sympathetic nervous system activation.