23Na NMR demonstrates prolonged increase of intracellular sodium following transient regional ischemia in the in situ pig heart

This study tests the hypothesis that Na-i(+) increases during regional ischemia in the in situ pig heart. An extracorporeal shunt was created between the carotid artery and the left anterior descending artery of 14 open chest pigs. Na-23 and P-31 NMR spectroscopy measured myocardial Na-i(+) and high energy phosphates (HEPs). The protocol consisted of three 40 min periods: pre-ischemia (shunt pressure, 76 +/- 23 mmHg (S.D.)), ischemia (shunt pressure, 25 +/- 7 mmHg), and post-ischemia (shunt pressure, 53 +/- 11 mmHg). The pre-ischemia Na-i(+) concentration was 6.7 +/- 4.2 mM. Phosphocreatine (PCr) was 15.3 +/- 0.5 mM, ATP 9.4 +/- 0.4 mM, inorganic phosphate (Pi) 1.5 +/- 0.2 mM, and pH(i) 7.16 +/- 0.09. At the end of ischemia Na-i(+) had increased to 10.5 +/- 2.8 mM (p < 0.0002): PCr decreased to 5.9 +/- 2.1 mM (p < 0.0002); ATP was 6.5 +/- 0.5 mM (p < 0.003); Pi had increased to 6.3 +/- 1.0 mM (p < 0.0002), and pH(i) was 6.41 +/- 0.06 (p < 0.0002). During the first 10 min of the reperfusion, Na-i(+) increased further to 12.4 +/- 2.8 mM (p < 0.025), whereas HEPs all returned to pre-ischemic values. Na-i(+) increases during regional ischemia in the in situ pig heart, suggesting reduced Na+/K+ ATPase activity. While ATP probably does not limit Na+/K+ ATPase activity, increases in Pi and decreases in pH(i) may reduce Na+/K+ AT-Pase activity. Additional Na-i(+) increases during reperfusion suggest either augmented Na+ influx or decreased Na+ efflux.