Hydroxyl radical-induced acute diastolic dysfunction is due to calcium overload via reverse-mode Na(+)-Ca(2+) exchange.
Circ Res
; 90(9): 988-95, 2002 May 17.
Article
em En
| MEDLINE
| ID: mdl-12016265
ABSTRACT
Hydroxyl radicals (OH) are involved in the development of reperfusion injury and myocardial failure. In the acute phase of the OH-mediated diastolic dysfunction, increased intracellular Ca(2+) levels and alterations of myofilaments may play a role, but the relative contribution of these systems to myocardial dysfunction is unknown. Intact contracting cardiac trabeculae from rabbits were exposed to OH, resulting in an increase in diastolic force (F(dia)) by 540%. Skinned fiber experiments revealed that OH-exposed preparations were sensitized for Ca(2+) (EC(50) 3.27+/-0.24 x 10(-6) versus 2.69+/-0.15 x 10(-6) mol/L; P<0.05), whereas maximal force development was unaltered. Western blots showed a proteolytic degradation of troponin T (TnT) with intact troponin I (TnI). Blocking of calpain I by MDL-28.170 inhibited both TnT-proteolysis and Ca(2+) sensitization, but failed to prevent the acute diastolic dysfunction in the intact preparation. The OH-induced diastolic dysfunction was similar in preparations with intact (540+/-93%) and pharmacologically blocked sarcoplasmic reticulum (539+/-77%), and was also similar in presence of the L-type Ca(2+)-channel antagonist verapamil. In sharp contrast, inhibition of the reverse-mode sodium-calcium exchange by KB-R7943 preserved diastolic function completely. Additional experiments were performed in rat myocardium; the rise in diastolic force was comparable to rabbit myocardium, but Ca(2+) sensitivity was unchanged and maximal force development was reduced. This was associated with a degradation of TnI, but not TnT. Electron microscopic analysis revealed that OH did not cause irreversible membrane damage. We conclude that OH-induced acute diastolic dysfunction is caused by Ca(2+) influx via reverse mode of the sodium-calcium exchanger. Degradation of troponins appears to be species-dependent but does not contribute to the acute diastolic dysfunction.
Buscar no Google
Base de dados:
MEDLINE
Assunto principal:
Cálcio
/
Radical Hidroxila
/
Trocador de Sódio e Cálcio
/
Diástole
/
Ventrículos do Coração
Limite:
Animals
Idioma:
En
Ano de publicação:
2002
Tipo de documento:
Article