Abstract |
Perfusion of the rat right ventricular wall muscle for 4 min with a Ca2(+)-free medium followed by perfusion with a Ca2(+)-containing solution resulted in a 42% recovery of developed tension, contracture, and a massive release of creatine phosphokinase (CPK) and lactate dehydrogenase (LDH) from the muscle. High concentrations (1-5 mM) of amiloride partially protected the ventricular wall from Ca2+ paradox-induced dysfunction. The inclusion of benzamil, an amiloride analogue, 2 min before and during the Ca2(+)-free perfusion period prevented contracture development, restored force development, and almost totally eliminated the release of CPK and LDH from the muscle. Contractile function was best protected by 10-50 microM benzamil. The results demonstrate the efficacy of benzamil as a protective agent against Ca2+ paradox-induced myocardial dysfunction and damage. In view of the known capacity of benzamil to block transsarcolemmal Na(+)-Ca2+ exchange, this study supports the involvement of elevated intracellular Na+ and a stimulation of Na(+)-Ca2+ exchange in this model of cardiac pathology.
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Authors | G N Pierce, T G Maddaford, E A Kroeger, E J Cragoe |
Journal | The American journal of physiology
(Am J Physiol)
Vol. 258
Issue 1 Pt 2
Pg. H17-23
(Jan 1990)
ISSN: 0002-9513 [Print] United States |
PMID | 2301606
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- benzamil
- Ouabain
- Amiloride
- Sodium
- Calcium
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Topics |
- Amiloride
(analogs & derivatives, pharmacology)
- Animals
- Calcium
(metabolism)
- Heart Diseases
(etiology, pathology, prevention & control)
- Male
- Myocardial Contraction
(drug effects, physiology)
- Myocardium
(enzymology, metabolism)
- Osmolar Concentration
- Ouabain
(pharmacology)
- Rats
- Rats, Inbred Strains
- Sarcolemma
(metabolism)
- Sodium
(metabolism)
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