Biomedical subjects
Publications and source records attributed to J F Ashruf.
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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.
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Hypertrophic hearts contain areas of hypoperfusion which can be visualized by increased NADH surface fluorescence during in vitro perfusion without oxygen-carrying particles under constant pressure and pacing. By contrast, fluorescence remained low when non-hypertrophic hearts were used instead. When during perfusion of normal hearts the pH of the medium was lowered from 7.5 to 7.0, areas of high fluorescence appeared in a few minutes. The high fluorescent areas under conditions of cardiac hypertrophy or pH 7.0 perfusion could be reduced by addition of superoxide dismutase. It indicates that oxygen free radicals interfere with proper flow regulation in areas of low pH. Fluorescence in hypertrophic hearts also diminished during addition of albumin-bound oleate to the standard, glucose-containing, medium. This is in agreement with our earlier finding of fatty acid protection from acidosis-initiated loss of capillary flow (Biochim. Biophys. Acta, 1033 (1990) 214-218). In contrast to low concentrations of free fatty acids, high concentrations interfere with tissue oxygenation. This has been illustrated by the use of 1 mM octanoate, which after a few min caused the appearance of high fluorescent areas. We conclude that decompensation of flow in hypoperfused areas of heart, as occurs in hypertrophy, may be stimulated by acidosis and oxygen free radicals.
Heterogeneity in the hypoxic state of Tyrode-perfused rat hearts was studied using NADH and Pd-porphine videofluorometry. Ischemic as well as high-flow anoxia resulted in a homogeneous rise of tissue NADH fluorescence, whereas normoxic recovery from both types of anoxia caused transiently persisting patchy fluorescent areas. Patterns were always the same for a given heart. PO2 distribution in the vasculature measured by Pd-porphine phosphorescence showed patterns similar to the NADH fluorescence patterns. Microsphere embolization of the capillaries, but not of arterioles, elicited identical NADH fluorescence patterns as seen during recovery from anoxia without microspheres. High heartbeat rates also caused patchy fluorescent areas but not in the presence of adenosine. Patterns corresponded to those seen during normoxic recovery from anoxia under low beat rates. It is concluded that there are circulatory units in the rat heart at the capillary level that result in the temporary persistence of anoxic areas during recovery from anoxia. These vulnerable areas are the first to be compromised during high heartbeat rates.
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