Author + information
- Received December 2, 1991
- Revision received June 4, 1992
- Accepted June 8, 1992
- Published online December 1, 1992.
- Howard P. Grill, MD, FACC∗,1,
- Jay L. Zweier, MD2,
- Periannan Kuppusamy, PhD,
- Myron L. Weisfeldt, MD, FACC and
- John T. Flaherty, MD, FACC∗
- ↵∗Address for correspondence: John T. Flaherty, MD, 500 Halsted, Johns Hopkins Hospital, 600 North Wolfe Street, Baltimore, Maryland 21205.
Objectives. The purpose of this study was to determine whether postischemic reperfusion of the heart in living rabbits induces a burst of oxygen free radical generation that can be attenuated by recombinant human superoxide dismutase administered at the moment of reflow.
Background. This phenomenon was previously demonstrated in crystalloid perfused, globally ischemic rabbit hearts.
Methods. Thirty-two open chest rabbits were assigned to one of four groups of eight animals each: Group I (control animals), no coronary artery occlusion; Group II, 30 min of circumflex marginal coronary artery occlusion without reperfusion; Group III, 30 min of coronary occlusion followed by 60 s of reperfusion, and Group IV, 30 min of coronary occlusion followed by treatment with recombinant human superoxide dismutase (a 20-mg/kg body weight bolus 90 s before reperfusion and a 0.17-mg/kg infusion during 60 s of reperfusion). Full thickness biopsy specimens taken from the ischemic region were then rapidly freeze clamped and electron paramagnetic resonance spectroscopy was performed at 77 °K.
Results. Three radical signals similar to those previously identified in the isolated, crystalloid perfused rabbit heart were observed: an isotropic signal with g = 2.004 suggestive of a semiquinone, an anisotropic signal with gI= 2.033 and gI= 2.005 suggestive of an oxygen-centered alkyl peroxy radical, and a triplet with g = 2.000 and aN= 24 G suggestive of a nitrogencentered radical. In addition, a fourth signal consistent with an iron-sulfur center was seen. The oxygen-centered free radical concentration during normal perfusion (Group I) was 1.8 ± 0.8 μmol compared with 4.4 ± 0.9 μmol after 30 min of regional ischemia without reperfusion (Group II) and 13.0 ± 2.5 μmol after 60 s of reperfusion (Group III) (p < 0.05 among all three groups). In contrast, superoxide dismutase treated-rabbits (Group IV) demonstrated a peak oxygen radical concentration of only 5.9 ± 1.2 μmol (p < 0.05 vs. Group III).
Conclusions. This study demonstrates that reperfusion after regional myocardial ischemia in the intact rabbit is associated with a burst of oxygen-centered free radicals. The magnitude of this burst is greater than that seen after a comparable duration of global ischemia in the isolated, buffer-perfused rabbit heart preparation and is significantly reduced by superoxide dismutase administration begun just before reflow.
↵∗ Current address: Allegheny General Hospital, 320 East North Avenue, Pittsburgh, Pennsylvania 15212.
↵1 Dr. Grill was supported by un Institutional Training Grant T32 HL07227 from the National Institutes of Health.
↵2 Dr. Zweier was supported by a National Institutes of Health Grant HL-38324 and is an Established Investigator of the American Heart Association, Dallas, Texas.
☆ This study was supported by a Specialized Center of Research in Ischemic Heart Disease Grant P50HL-17655 from the National Institutes of Health, Bethesda, Maryland.
☆☆ This report was presented in part at the 60th Annual Scientific Sessions of the American Heart Association, Anaheim, California, October 1987 and the 37th Annual Scientific Session of the American College of Cardiology, Atlanta, Georgia. March 1988.
- Received December 2, 1991.
- Revision received June 4, 1992.
- Accepted June 8, 1992.