ISSN:
1435-1803
Keywords:
Ischaemia
;
bound inorganic phosphate
;
fre inorganic phosphate
;
contractile failure
;
magnetic resonance
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Abstract Inorganic phosphate (Pi) accumulates extremely rapidly in ischaemic heart muscle and intracellular binding of this metabolite may account for the precipitous loss of function seen at the onset of severe ischaemia. We have used31P-NMR spectroscopy to measure the free cytosolic [Pi] and chemical assay techniques to measure total tissue Pi at 0, 1, 2, 3, 5, and 12 min of complete global ischaemia in the isolated isovolumic rat heart. At zero time, the Pi assayed chemically was 30.77±5.52 μmol/g dry wt (mean±SD, n=7) whilst Pi assayed by NMR was 3.39±1.21 μmol/g dry wt (n=15). Thus, 27.38 μmol/g dry wt of Pi was bound at a cytosolic [Pi] of 0.82 mM. After 12 min of ischaemia, 49.88 μmol/g dry wt of Pi was bound at a cytosolic [Pi] of 4.11 mM. When all data were fitted, using a non-linear, least squares fit (p〈0.05), to the binding isotherm: Bound Pi=B′max. [Pi]/(K′d+[Pi]), the apparent binding parameters K′d and B′max were estimated to be 1.1±0.6 mM and 64.0±10.2 μmol/g dry wt respectively. During the first minute of global ischaemia when the rate-pressure product had decreased by 79% of its pre-ischaemic value, bound Pi had increased by 58% and free cytosolic [Pi] by 162%. When functional and metabolite changes were expressed as a fraction of the total change which occurred during the 12-min ischaemic period, bound Pi had the profile most similar to the rate-pressure product. Both the amount of bound Pi and free cytosolic [Pi] correlated with loss of contractile function as the ischaemic period progressed. The results snow that during ischaemia, Pi is bound progressively as free cytosolic [Pi] is increased as the result of high energy phosphate hydrolysis. While these results are consistent with the possibility that Pi binding may contribute to ischaemic contractile failure, no molecular explanation for the possible effect of bound Pi on contraction has been propsed.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF00788541
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