The role of accumulation of sodium and calcium on contractile failure of the hypoxic/reoxygenated heart.
The present study was undertaken to determine whether myocardial energy or ion levels are related to oxygen-replenishment-induced recovery of cardiac contractile force after hypoxia. Isolated rat hearts were perfused for 3 to 40 min under hypoxic conditions, followed by 45 min of reoxygenation. Hypoxia induced a cessation of cardiac contractile force, a rise in resting tension, a decrease in high energy phosphates, and an increase in lactate. Myocardial ATP, creatine phosphate (CP) and lactate reached steady-state levels after 15, 10 and 5 min of hypoxia, respectively. Hypoxic conditions in the present study also caused an increase in sodium content and a decrease in potassium content, but not changes in calcium content, along with a prolonged hypoxic period. When the hearts were perfused for more than 25 min under hypoxic conditions, no recovery of contractile force was observed following 45-min of reoxygenation. Hypoxic perfusion for more than 25 min induced an accumulation of tissue sodium content approximately 3 fold higher than the pre-hypoxic value at the end of hypoxia, and also induced a marked increase in myocardial calcium content upon reoxygenation. When tissue sodium content accumulated by less than 300% of the pre-hypoxic value, cardiac contractile function was partially reversed by reoxygenation and calcium-overload was not observed. The recovery of post-hypoxic cardiac contractility correlated with tissue sodium content during hypoxia rather than with myocardial high energy phosphate content at the end of hypoxia. These results suggest that accumulation of tissue sodium content in the hypoxic myocardium and calcium content in the reoxygenated myocardium may be indicative of hypoxia/reoxygenation-induced cardiac contractile failure.
Tanonaka
K
K
Department of Pharmacology, Tokyo University of Pharmacy and Life Science, Japan.
Niwa
T
T
Takeo
S
S
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002463:Cell Membrane Permeability; D004734:Energy Metabolism; D000860:Hypoxia / Q000378:metabolism*; D066298:In Vitro Techniques; D007473:Ion Channels / Q000378:metabolism; D007773:Lactates / Q000378:metabolism; D019344:Lactic Acid; D008297:Male; D009200:Myocardial Contraction / Q000502:physiology*; D009206:Myocardium / Q000378:metabolism*; D010477:Perfusion; D010710:Phosphates / Q000378:metabolism; D010725:Phosphocreatine / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012964:Sodium / Q000378:metabolism*
D007473:Ion Channels; D007773:Lactates; D010710:Phosphates; D010725:Phosphocreatine; D019344:Lactic Acid; D000255:Adenosine Triphosphate; D012964:Sodium; D002118:Calcium