Circulation, Vol 75, 282-291, Copyright © 1987 by American Heart Association
G Ambrosio, ML Weisfeldt, WE Jacobus and JT Flaherty
It has been suggested that the beneficial effects of reperfusing ischemic
myocardium might be in part reversed by the occurrence of "reperfusion
injury." One possible mechanism could be the generation of oxygen free
radicals. Superoxide dismutase enzymatically scavenges superoxide radicals
by dismutation to hydrogen peroxide. This study tested the hypothesis that
administration of recombinant human superoxide dismutase (h-SOD) at the
time of reflow after a period of prolonged global ischemia would result in
improved recovery of myocardial metabolism and function by preventing or
reducing a potentially harmful component of reperfusion. We also sought to
determine whether catalase, an enzymatic scavenger of hydrogen peroxide,
was a necessary addition for optimal benefit. Langendorff perfused rabbit
hearts were subjected to 30 min of normothermic (37 degrees C) total global
ischemia. At the moment of reperfusion, 12 control hearts received a 10 ml
bolus of normal perfusate followed by 15 min of reperfusion with normal
perfusate (group I), 12 hearts received 60,000 IU of h-SOD as a bolus
followed by a continuous infusion of 100 IU/ml for 15 min (group II), and
12 hearts received 60,000 IU of h-SOD and 60,000 IU of catalase as a bolus
followed by 100 IU/ml of both enzymes for 15 min (group III). Myocardial
ATP and phosphocreatine (PCr) content and intracellular pH during ischemia
and reperfusion were continuously monitored with 31P nuclear magnetic
resonance (NMR) spectroscopy. During 30 min of normothermic global ischemia
intracellular pH dropped from 7.11-7.18 to 5.58-5.80 in all three groups of
hearts. Likewise myocardial PCr content fell rapidly to 7% to 8% and ATP
fell more slowly to 29% to 36% of preischemic control content. After 45 min
of reperfusion PCr recovered to 65 +/- 5% of control in untreated (group I)
hearts compared with 89 +/- 8% in h-SOD- treated (group II) hearts (p less
than .01 vs group I) and with 83 +/- 6% of control in
h-SOD/catalase-treated (group III) hearts (p less than .05 vs group I).
Recovery of isovolumic left ventricular developed pressure was 68 +/- 5% of
control in h-SOD-treated (group II) hearts and 66 +/- 6% of control in
h-SOD/catalase-treated (group III) hearts after 45 min of reflow, compared
with 48 +/- 6% of control in untreated (group I) hearts (p less than .005
for groups II and III vs group I). The NMR data confirmed equal depletion
of ATP and PCr content in all three groups of hearts.(ABSTRACT TRUNCATED AT
400 WORDS)
ARTICLES
Evidence for a reversible oxygen radical-mediated component of reperfusion injury: reduction by recombinant human superoxide dismutase administered at the time of reflow
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