Sodium imbalance as a cause of calcium overload in post-hypoxic reoxygenation injury.
In hypoxic-reoxygenation injury, Ca2+ overload is preceded by disturbed Na+ balance, with low activity of the Na+ pump during hypoxia and during reoxygenation. Failure to correct Na+ content rapidly upon reoxygenation might lead to Ca2+ overload by Na+-Ca2+ exchange. This possibility was tested in energy-replete myocardium by perfusing with low K+ (0.6 mM) medium to inhibit the Na+ pump throughout a two-stage procedure with low Ca2+ (0.15 mM) in the perfusate, so that Na+ loading occurred prior to excess Ca2+ uptake, as is the case in hypoxia, then with normal Ca2+ (1.3 mM) to allow Ca2+ uptake, as occurs in reoxygenation after hypoxia. Twenty minutes of Na+-loading (stage a) produced cell Na+ and tissue K+ levels similar to those after 40 min hypoxia. In stage b, hearts rapidly developed Ca2+ overload (12.6 +/- 0.90 microns/g dry wt), low ATP (4.8 +/- 0.8 microns/g dry wt), and creatine kinase release (peak 3.5 +/- 1.2 U/min/g dry wt). These values were comparable to those occurring with reoxygenation after 40 min hypoxia (Ca2+ 10.1 +/- 1.09 microns/g dry wt, ATP 6.3 +/- 0.8 microns/g dry wt, creatine kinase peak 2.1 +/- 0.5 U/min/g dry wt). Contractile failure at high resting tension occurred in both groups. In contrast, hearts recovered well from a period of Na+ pump inhibition which was only temporary. This suggests that Na+-Ca2+ exchange could account for Ca2+ overload in reoxygenation injury on the basis of Na+ pump depression developing during hypoxia and sustained in reoxygenation.(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D001693:Biological Transport, Active; D002118:Calcium / Q000378:metabolism*; D009202:Cardiomyopathies / Q000209:etiology* / Q000378:metabolism; D000860:Hypoxia / Q000378:metabolism*; D007424:Intracellular Fluid / Q000378:metabolism; D008297:Male; D008954:Models, Biological; D009200:Myocardial Contraction; D010100:Oxygen / Q000378:metabolism*; D010710:Phosphates / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D012964:Sodium / Q000378:metabolism*; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism
D010710:Phosphates; D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase; D010100:Oxygen; D002118:Calcium