EFFECTS OF ISCHEMIA ON INTRACELLULAR SODIUM AND PHOSPHATES IN THE IN-VIVO RAT-LIVER

Metabolic factors that influence the transition from reversible to irr eversible ischemic injury were studied in the rat liver in vivo with P -31-nuclear magnetic resonance (NMR) spectroscopy. Hepatic ischemia fo r 15, 35, or 65 min was produced by occlusion of the hepatic artery an d portal vein in rats. Ischemia caused a rapid decrease in the ATP con centration ([ATP])-to-P-i concentration ratio and pH within 5 min, but there was little change in these variables detectable by P-31-NMR wit h longer periods of ischemia. After reperfusion, the [ATP] and P-i con centration returned toward normal values in livers exposed to 15 or 35 min of ischemia, but 65 min of ischemia were associated with only mod est recovery in [ATP], and the [ATP] later decreased. Because the P-31 -NMR spectrum was similar after brief compared with prolonged ischemia , it appears that neither ATP depletion, P-i accumulation, nor acidosi s predicts metabolic recovery. Hepatic intracellular Na+ was also meas ured in separate groups of animals by Na-23-NMR in the presence of a s hift agent, thulium (III) ododecane-1,4,7,10-tetrakis(methylene-phosph onate) (TmDOTP5-), and by atomic absorption spec troscopy. Under basel ine conditions, the concentration of intracellular Na+ was 15.2 mM by atomic absorption spectroscopy and 16.5 mM by Na-23-NMR. Although the P-31-NMR spectrum responded very rapidly to the onset of ischemia, int racellular Na+ concentration measured by Na-23-NMR increased gradually but steadily at similar to 1.0 mM/min during early (up to 15 min) isc hemia. These observations demonstrate that a rise in intracellular Na does occur during early ischemia, that TmDOTP5- can be applied in viv o for analysis of intracellular Na+ in the ischemic liver, and that P- 31-NMR spectroscopy is very sensitive to early ischemic injury.