title: Calcium inhibition of glycolysis contributes to ischaemic injury.
abstract: OBJECTIVE
  The purpose of the study was to confirm that [Ca2+]i and .[H+]i increase during ischaemia in hypertensive hearts but not in thyrotoxic hearts, and that the rise in [Ca2+]i and [H+]i inhibits glycolysis, causing a rise in phosphomonoester sugars and thereby influencing postischaemic recovery.
  
  
  METHODS
  Rats were made hypertensive by aortic banding and thyrotoxic by injection of L-thyroxine. [Ca2+]i was studied in isolated hearts by surface fluorometry assessing calcium dependent changes in the fluorescent dye INDO-1, while [pH]i and phosphomonoester sugars were studied by 31P nuclear magnetic resonance (NMR). Global ischaemia was carried out by turning off all flow to the heart for 30 min. Hearts were then reperfused for 30 min.
  
  
  METHODS
  72 Sprague-Dawley rats, weight 500-600 g, were used. Left ventricular hypertrophy was generated by aortic banding in 36, half of which were treated with verapamil. Eighteen were injected with L-thyroxine and there were 18 controls.
  
  
  RESULTS
  With all groups, developed pressure immediately declined after the onset of global ischaemia. During ischaemia the phosphomonoester sugars rose less in the hearts of thyrotoxic rats and the verapamil treated aortic constricted rats than in those of untreated aortic constricted and normal rats. During ischaemia there was no significant difference in [pH]i among the four groups. During ischaemia intracellular calcium rose least in thyrotoxic and verapamil treated aortic constricted rats, and most in untreated aortic constricted and normal rats. Intracellular calcium rose 10-15 min after the onset of ischaemia in verapamil treated pressure overload and control hearts; calcium rose immediately after the onset of ischaemia in the untreated aortic constricted hearts, but negligibly in hearts from thyroxine treated animals. Verapamil treatment of the aortic constricted hearts prevented the rise in intracellular calcium, and attenuated phosphomonoester sugar accumulation. Postischaemic recovery was complete in hearts in thyroxine treated and verapamil treated aortic constricted rats, but not in hearts from untreated aortic constricted and normal rats. Postischaemic recovery was inversely related to ischaemic diastolic [Ca2+]i and phosphomonoester sugar levels, but was not related to ischaemic values for [pH]i.
  
  
  CONCLUSIONS
  Postischaemic recovery may depend on the ability of the cell to maintain mitochondrial activity as evidenced by oxygen consumption, thereby controlling the voltage of the cell, and influencing the ability of the myocardium to maintain its calcium homeostasis.
authors: Cardiovascular Research Institute, University of California San Francisco 94143.
authors: W
authors: W
authors: Auffermann
authors: S
authors: S
authors: Wagner
authors: S
authors: S
authors: Wu
authors: P
authors: P
authors: Buser
authors: W W
authors: WW
authors: Parmley
authors: J
authors: J
authors: Wikman-Coffelt
mesh_terms: D000818:Animals; D002118:Calcium / Q000502:physiology*; D003327:Coronary Disease / Q000378:metabolism*; D006019:Glycolysis / Q000502:physiology*; D006973:Hypertension / Q000378:metabolism*; D066298:In Vitro Techniques; D015425:Myocardial Reperfusion; D010101:Oxygen Consumption; D010732:Phosphofructokinase-1 / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013971:Thyrotoxicosis / Q000378:metabolism; D013974:Thyroxine / Q000494:pharmacology; D014700:Verapamil / Q000494:pharmacology
chemical_list: D014700:Verapamil; D010732:Phosphofructokinase-1; D013974:Thyroxine; D002118:Calcium