Calcium-linked adjustment of myocardial metabolism to changing mechanical demands in the isolated rat heart.
Isolated rat hearts perfused by the modified Langendorff technique were used to study the effects of changes in perfusate calcium concentration (Cap2+) on left ventricular mechanical performance, O2-consumption, NADH-fluorescence and lactate release in the presence of glucose or pyruvate as the sole exogenous substrate. Stepwise elevation of Ca2+ from 0.31 to 7.8 mM resulted in a continuous increase of contractile activity and O2-consumption independent of the substrate present. Redox changes similar to State 3 to 4  transition (NAD+ reduction) were observed when mechanical activity was reduced by perfusing the hearts with 0.65 or 0.31 mM Cap2+, which was also substrate independent. At high Cap2+ (2.6--7.8 mM) increase of contractile activity and O2-consumption was accompanied by Cap2+ dependent NAD+ reduction in the presence of glucose. Inhibition of glycolisis by pyruvate reversed the direction of NADH response (NADH oxidation following Cap2+ elevation). Myocardial lactate relealse was increased by elevation of Cap2+ from 1.3 to 5.2 mM in the presence of glucose, but this effect was significantly inhibited in the pyruvate perfused hearts. It is concluded that NADH signal originates from both the cytosolic and mitochondrial NADH compartment. The direction of NAD+/NADH redox state changes following Cap2+ elevation is grately influenced by the substrate  preferentially consumed by the heart. The data suggest that calcium increases the availability of reducing equivalents to the respiratory chain thereby ensuring adequate supply of ATP when myocardial mechanical demands are changing.
D000818:Animals; D002118:Calcium / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005947:Glucose / Q000378:metabolism; D066298:In Vitro Techniques; D007773:Lactates / Q000378:metabolism; D009200:Myocardial Contraction / Q000187:drug effects*; D009206:Myocardium / Q000378:metabolism*; D009243:NAD / Q000378:metabolism; D010101:Oxygen Consumption / Q000187:drug effects; D011773:Pyruvates / Q000378:metabolism; D051381:Rats
D007773:Lactates; D011773:Pyruvates; D009243:NAD; D005947:Glucose; D002118:Calcium