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The Journal of Thoracic and Cardiovascular Surgery, Vol 96, 930-938, Copyright © 1988 by The American Association for Thoracic Surgery and The Western Thoracic Surgical Association
K Bando, S Teramoto, M Tago, S Seno, T Murakami, S Nawa and Y Senoo
The effect of free radical scavengers on free radical-induced myocardial
injury during heart preservation and transplantation was examined. Four
groups of nine hearts each were harvested from mongrel dogs (12.5 to 16.5
kg) and orthotopically transplanted to size-matched recipients. All hearts
received a continuous perfusion of oxygenated modified Collins' solution
(group A). In addition, groups B, C, and D received Fluosol DA and albumin.
Preservation perfusion was performed for 18 hours, at 4 degrees C, pH =
7.4, and 20 mm Hg. In group C, recombinant human superoxide dismutase
(4,080 U/mg, 20 mg/kg) and bovine catalase (46,200 U/mg, 20 mg/kg) were
administered only during preservation perfusion. In group D, these
scavengers were administered just before and during reperfusion for 1 hour.
Hemodynamic studies were performed before excision of the donor hearts and
1 hour after the termination of cardiopulmonary bypass. Creatinine kinase
MB isoenzyme and thiobarbituric acid reactive substance levels in the
coronary effluent were determined during preservation perfusion and
reperfusion. Only group A showed a significant heart weight gain (p less
than 0.05) and a decline in passive compliance (p less than 0.05) during
preservation. Lactate release was higher in group A than in the groups
receiving Fluosol DA. In contrast, pyruvate levels in group A were lower
than in other groups. The generation of free radicals stayed at a low level
during preservation, but significantly increased during reperfusion and was
associated with a corresponding increase in creatinine kinase MB isoenzyme.
Perfusion with a perfluorochemical solution (group B) inhibited the sharp
rise in levels of thiobarbituric acid reactive substances and of creatinine
kinase MB isoenzyme and improved cardiac function during reperfusion
(versus group A). Exogeneous free radical scavengers administered just
before and during reperfusion (group D) significantly ameliorated
thiobarbituric acid reactive substances and creatinine kinase MB isoenzyme
levels and also induced a significant hemodynamic improvement during
reperfusion. However, administration of scavengers during preservation did
not. This study demonstrates that the generation of free radicals is
primarily significant during reperfusion and reoxygenation after ischemia.
Thus the best time for administration of scavengers is just before and just
after the onset of reperfusion. Furthermore, perfusion with
perfluorochemicals effectively maintains aerobic metabolism and ameliorates
free radical damage during this period.
ARTICLES
Oxygenated perfluorocarbon, recombinant human superoxide dismutase, and catalase ameliorate free radical induced myocardial injury during heart preservation and transplantation
Department of Surgery II, Okayama University Medical School, Japan.
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