Cell swelling, sodium fluxes, membrane permeability and high energy
phosphates in isolated rat hearts during hypothermic ischemia -
multinuclear nmr studies.
Askenasy, Nadir, Antonio Vivi, Maria Tassini, and Gil Navon.
School of Chemistry, Tel Aviv University, Tel Aviv 69978,
Israel
APStracts 2:0201H, 1995.
Intracellular sodium accumulation, cellular swelling and energy
deficiency are ischemia-associated processes which participate in the
transition to an irreversible ischemic injury. This study aims to
determine the relationship between these parameters in intact rat
hearts, during global ischemia at 4oC. High energy phosphates were
determined by 31P NMR, intracellular sodium accumulation was measured
by 23Na spectroscopy with the shift reagent Dy(TTHA)3-, and cell
volumes were measured by 59Co and 1H spectroscopy using the
extracellular marker Co(CN)63-. Intracellular sodium flux was
composed of three rates: 1.53 SYMBOL 177 \f "Symbol" 0.17, 0.17
SYMBOL 177 \f "Symbol" 0.05 and 0.30 SYMBOL 177 \f "Symbol" 0.06
mol/gdw during the periods 0-1.5, 2-7 and 9-12 hours, respectively.
Sodium influx resulted in accumulation of the ion: 10% after 4 hours,
16% after 10 hours and 29% after 12 hours. Water followed sodium into
the cells at two constant molar ratios: Na/H2O=3.80 SYMBOL 177 \f
"Symbol" 0.15 SYMBOL 180 \f "Symbol" 10-3 during the first 8 hours of
ischemia and Na/H2O=7.8 10 during the period 8-12 hours. Relative to
the initial intracellular volume, cells swelled by 38% after 8 hours
and 46% after 12 hours; reperfusion reduced cellular swelling to 25%
and 36%, respectively. The last 4 hours of storage were characterized
by: a) absence of high energy phosphates; b) increased Na influx rate
and sodium accumulation; c) increased Na/H2O portion indicating an
enhanced efflux of intracellular components; d) preserved membrane
selectivity for the extracellular markers Dy(TTHA)3- and Co(CN)3-; e)
deterioration of the haemodynamic function: LVP 75% and 40%,
initiation of activity 8 min and 26 min for 8 or 12 hours of
ischemia, respectively. These data indicate that changes in the
membrane selectivity and permeability occur during hypothermic
ischemia, and are associated in time with depletion of the energy
stores and causing deterioration of the functional recovery. It is
suggested that these changes in permeability signal the onset of a
gradual deterioration in membrane integrity.
Received 29 September 1994; accepted in final form 3 April 1995.
APS Manuscript Number H883-4.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 26 May 1995.