title: Increase of cardiac work is associated with decrease of mitochondrial NADH.
abstract: In this study we investigated the effect of work and substrate supply on mitochondrial NADH/NAD+ using epicardial autofluorescence in rat hearts perfused according to Langendorff. To avoid vasoconstrictor effects during high work output, nitroprusside-containing Tyrode solution was used. Photobleaching was avoided by using discontinuous ultraviolet excitation for NADH fluorescence measurements. To increase work, heartbeat rate was raised from 5 to 7 Hz, and concomitantly left ventricular pressure was raised stepwise from 0 to +/- 90 mmHg. During substrate-limited (5.5 mM glucose) perfusions, increase in O2 consumption (3.5 +/- 0.4 mumol.min-1.g-1, mean +/- SE, n = 6) caused by increase of heartbeat rate was associated with a significant decrease of NADH fluorescence (-31 +/- 2.5%, mean +/- SE, n = 6). During perfusions with 10 mM pyruvate increase of O2 consumption (3.6 +/- 0.7 mumol.min-1.g-1, mean +/- SE, n = 6) was associated with significant decrease of NADH fluorescence (-20 +/- 2.6%, mean +/- SE, n = 6). These results suggest that a rise in mitochondrial NADH/NAD+ is not the primary stimulus for increase in respiration and that changes of mitochondrial NADH/NAD+ are secondary to changes in O2 consumption.
authors.affiliation: Department of General Surgery, Erasmus University, Rotterdam, The Netherlands.
authors.forename: J F
authors.initials: JF
authors.lastname: Ashruf
authors.forename: J M
authors.initials: JM
authors.lastname: Coremans
authors.forename: H A
authors.initials: HA
authors.lastname: Bruining
authors.forename: C
authors.initials: C
authors.lastname: Ince
mesh_terms: D000818:Animals; D002304:Cardiac Pacing, Artificial; D005453:Fluorescence; D006321:Heart / Q000502:physiology*; D006339:Heart Rate; D006439:Hemodynamics; D008297:Male; D008928:Mitochondria / Q000378:metabolism*; D009243:NAD / Q000378:metabolism*; D010084:Oxidation-Reduction; D010101:Oxygen Consumption / Q000187:drug effects; D011773:Pyruvates / Q000494:pharmacology; D019289:Pyruvic Acid; D051381:Rats; D017208:Rats, Wistar; D014466:Ultraviolet Rays
chemical_list: D011773:Pyruvates; D009243:NAD; D019289:Pyruvic Acid