Circulation, Vol 65, 561-570, Copyright © 1982 by American Heart Association
JT Flaherty, ML Weisfeldt, BH Bulkley, TJ Gardner, VL Gott and WE Jacobus
Phosphorus-31 nuclear magnetic resonance (31P NMR) can estimate tissue
intracellular pH as well as the content of high-energy phosphate
metabolites in isolated perfused hearts. We used 31P NMR to examine
mechanisms associated with the recovery of ventricular function in hearts
subjected to global ischemia and reperfusion, with special emphasis on
intracellular pH, a previously unreported variable. Single- dose and
multiple-dose administration of a hyperkalemic cardioplegic solution were
compared with hypothermia alone in 18 isolated perfused rabbit hearts.
Hearts in group 1 were subjected to 24 degrees C hypothermia during 60
minutes of global ischemia; group 2 hearts received a single injection of
37-mM KCL cardioplegic solution at 10 degrees C at the onset of ischemia;
and group 3 hearts received a similar initial cardioplegic injection
followed by two subsequent 24 degrees C injections at 20-minute intervals
during the ischemic period. Using an intraventricular balloon, maximal
dP/dt provided a quantitative index of left ventricular performance before
and after ischemia. Return of ventricular function expressed as a
percentage of control was 54 +/- 11% for group 1, 84 +/- 6% for group 2,
and 101 +/- 18% for group 3. Differences in the rate of development of
intracellular acidosis were noted during the 60-minute ischemic period.
Intracellular pH fell to 6.09 +/- 0.12 in group 1, 6.31 +/- 0.09 in group
2, an 6.79 +/- 0.03 in group 3. In all three groups intracellular pH
returned to control (pH 7.20) within 10 minutes of reflow. The metabolic
correlates of functional recovery appeared to be the tissue content of ATP
at the end of ischemia and after reflow. ATP content at the end of ischemia
was 22 +/- 2% of control in group 1 hearts, 31 +/- 4% in group 2 and 64 +/-
2% in group 3. After 45 minutes of reperfusion, ATP levels recovered to 33
+/- 9% of control in group 1, to 71 +/- 9% in group 2 and to 86 +/- 6% in
group 3. Although there were no differences between groups in the content
of creatine phosphate after 60 minutes of ischemia, the rates of creatine
phosphate decline were dissimilar. Further, during the early reflow period,
a marked overshoot in tissue creatine phosphate was detected, especially in
groups 1 and 2. Histologic damage assessed by light microscopy correlated
with the metabolic data, confirming that multidose cardioplegia provided
the best preservation of cellular morphology. These results demonstrate
that the magnitude of intracellular acidosis and the associated increase in
inorganic phosphate correlate inversely with recovery of postischemic
ventricular structure and function. ATP, but not creatine phosphate,
content correlates with return of contractile performance after
reperfusion. The overshoot in creatine phosphate during early reperfusion
might impede optimal restoration of ATP content and, as a result, optimal
recovery of cell functions.
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Mechanisms of ischemic myocardial cell damage assessed by phosphorus-31 nuclear magnetic resonance
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