Covalent linkage of
polyethylene glycol to
superoxide dismutase prolongs the serum half-life of the
enzyme and may facilitate intracellular access. We tested the myocardial protective effect of
polyethylene glycol superoxide dismutase administered once, 24 hours before
ischemia. Because hearts were studied ex vivo in a
crystalloid perfused system, cardioprotection could be ascribed to intramyocardial or membrane-bound
polyethylene glycol superoxide dismutase accumulation. Thirty isolated rabbit hearts from the four following groups were studied: (1) control: untreated rabbits (n = 7); (2) PEG-control: 24-hour intravenous preinfusion of
methoxypolyethylene glycol 5000 (5 mg/kg) to examine the effect of
polyethylene glycol alone, without conjugation to
superoxide dismutase (n = 8); (3)
PEG-SOD 10,000: 24-hour preinfusion of
polyethylene glycol superoxide dismutase (10,000 U/kg) (n = 8); (4)
PEG-SOD 30,000: 24-hour preinfusion of
polyethylene glycol superoxide dismutase (30,000 U/kg) (n = 7). After measurement of baseline function with use of an intraventricular balloon, hearts were subjected to normothermic
ischemia until a 4 mm Hg rise in intracavitary pressure was observed. Function was assessed at 15-minute intervals throughout reperfusion and expressed as percent return of developed pressure. After 60 minutes of reperfusion, recovery of function was greater for the
PEG-SOD 30,000 group (85.6% +/- 2.6%) when compared with either the untreated or PEG-control group (68.9% +/- 2.3% and 71.4% +/- 2.0%, respectively). A similar difference was seen throughout reperfusion. Although an improved return of function was shown in the lower dose
PEG-SOD 10,000 group, the margin of difference when compared with any of the control groups was determined to be insignificant at all times of reperfusion and at 60 minutes (75.9% +/- 3.2%). These data demonstrate that high, but not low, doses of
polyethylene glycol superoxide dismutase significantly reduce
reperfusion injury when administered 24 hours before initiation of global
ischemia. Moreover, since the perfusate was
superoxide dismutase free, this effect was most likely intramyocardial or membrane bound and therefore might be added to protection afforded by circulating
superoxide dismutase.