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Measurement of Cytosolic Ca2+ in Isolated Contractile Lymphatics
Published on: December 8, 2011
Volumes and Na+/H+ antiporter activity of lymphocytes in patients with congestive heart failure
1Medizinische Klinik, Klinikum Innenstadt, Ludwig-Maximilians-Universität, München, Germany.
Insights
Congestive heart failure patients show enlarged human mononuclear leukocytes (HML). Neither angiotensin-converting enzyme (ACE) inhibitor nor diuretic therapy normalized this cell volume abnormality, suggesting a structural change.
Area of Science:
- Cardiology
- Cell Biology
- Pharmacology
Background:
- Congestive heart failure (CHF) is associated with skeletal muscle abnormalities, including altered cellular volume and electrolytes.
- These cellular changes may contribute to peripheral vascular resistance dysregulation and clinical symptoms like muscular weakness in CHF.
- Previous treatments like diuretics and digoxin have been linked to these cellular abnormalities.
Purpose of the Study:
- To investigate the impact of angiotensin-converting enzyme (ACE) inhibitor therapy on cell volume and its regulation in CHF patients.
- To compare cell volume regulation in CHF patients treated with ACE inhibitors versus those on diuretics alone.
- To assess potential structural versus functional changes in cell volume regulation.
Main Methods:
- Measured electronic cell diameters of human mononuclear leukocytes (HML) using a Coulter Counter.
- Compared HML from CHF patients on ACE inhibitors (n=19) with those on diuretics (n=16) and normal volunteers (n=20).
- Assessed Na+/H+ antiporter activity via cell swelling in isotonic propionate, sensitive to ethylisopropylamiloride.
Main Results:
- HML diameters were significantly increased in both CHF patient groups compared to normal controls (P < 0.01 for ACE inhibitors, P < 0.05 for diuretics).
- No significant correlation was found between ejection fraction or digoxin therapy and average cell diameters.
- Ethylisopropylamiloride-sensitive swelling rates were normal in both patient groups, indicating normal Na+/H+ antiporter activity.
Conclusions:
- Increased HML size in CHF patients represents a structural cellular change, not a rapidly reversible functional abnormality.
- Neither ACE inhibitor therapy nor diuretic therapy significantly altered this increased cell size.
- Cell volume regulation, specifically Na+/H+ antiporter activity, appears preserved despite structural changes in HML.
Abstract:
Previous studies in patients with congestive heart failure (CHF) treated with diuretics and/or digoxin have shown abnormalities of cellular volume and electrolytes in biopsies of skeletal muscle. These abnormalities seem to play an important role with regard to the dysregulation of peripheral vascular resistance and characteristic clinical features of CHF, for example, muscular weakness. This study assessed the effect of angiotension-converting enzyme (ACE) inhibitor therapy on cell volume and cell volume regulation in patients with CHF. Cell diameters of human mononuclear leukocytes (HML) were determined electronically by a Coulter Counter. Cell diameters for 19 patients with decreased left ventricular ejection fraction (determined via levocardiography) on therapy with ACE inhibitors (group 1) were compared to those of HML from patients on diuretics alone (group 2, n = 16). The activity of the Na+/H+ antiporter was determined by cell swelling in isotonic propionate. The control group consisted of 20 normal, age- and sex-matched volunteers. HML diameters were significantly increased from 7.16 +/- 0.07 in normals to 7.24 +/- 0.08 microns (group 1; P < 0.01) and 7.23 +/- 0.11 microns (group 2; P < 0.05), indicating an abnormal regulation of cell volume. There were no statistically significant correlations between the individual ejection fraction or digoxin therapy and average cell diameters. In both patient groups ethylisopropylamiloride-sensitive swelling rates were normal compared to the control group indicating a normal activity of the Na+/H+ antiporter. In conclusion, increased cell sizes reflect a structural change in HML rather than a rapidly reversible functional abnormality which was not affected different by ACE inhibition and diuretic therapy.(ABSTRACT TRUNCATED AT 250 WORDS)
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