The present study aims to determine the volume-related activities of
sodium ion transporters in the rat heart. Intracellular volumes were measured in isolated hearts by 1H of water and 59Co nuclear magnetic resonance (NMR) of the extracellular marker cobalticyanide. Inhibition of the Na-K-
adenosinetriphosphatase pumps with 50 microM
ouabain did not affect the extent of cellular swelling during 30 min of
ischemia: cells swelled by 0.37 ml/g dry wt compared with the controls (0.38 ml/g dry wt). After perfusion with 400 microM
ouabain or 200 microM iodoacetate, the cells shrank during
ischemia (from 2.50 +/- 0.06 to 2.20 +/- 0.09 and 2.28 +/- 0.07 ml/g dry wt, respectively). Inhibition of passive
sodium ion transporters reduced cellular swelling during
ischemia: pretreatment (10 min) with 100 microM
furosemide (Na-K-2Cl cotransport), 1.5 microM
ethylisopropylamiloride (Na/H antiport), and 50 microM
lidocaine (
sodium channels) led to swelling of 0.27, 0.21, and 0.13 ml/g dry wt, respectively. The extent of cellular water accumulation was apparently correlated with the onset and maximal force of the
ischemic contracture, unlike the data of hearts treated with
ouabain and iodoacetate. The blockage of each of the passive
sodium transporters improved the recovery of intracellular volumes at reperfusion, indicating that in the heart these pathways are responsible for the sustained reperfusion cellular
edema. It is concluded that acute cellular swelling during
myocardial ischemia is not caused by insufficiency of the Na-K pumps but is partially mediated by systems that transport
sodium into the cells.