Recombinant human superoxide dismutase (h-SOD) fails to improve recovery of ventricular function in patients undergoing coronary angioplasty for acute myocardial infarction

John T. Flaherty; Bertram Pitt; John W. Gruber; Richard R. Heuser; Donald A. Rothbaum; Lawrence R. Burwell; Barry S. George; Dean J. Kereiakes; David Deitchman; Nancy Gustafson; Jeffrey A. Brinker; Lewis C. Becker; G. B.John Mancini; Eric Topol; Steven W. Werns

doi:10.1161/01.CIR.89.5.1982

Recombinant human superoxide dismutase (h-SOD) fails to improve recovery of ventricular function in patients undergoing coronary angioplasty for acute myocardial infarction

John T. Flaherty, Bertram Pitt, John W. Gruber, Richard R. Heuser, Donald A. Rothbaum, Lawrence R. Burwell, Barry S. George, Dean J. Kereiakes, David Deitchman, Nancy Gustafson, Jeffrey A. Brinker, Lewis C. Becker, G. B.John Mancini, Eric Topol, Steven W. Werns

Research output: Contribution to journal › Article › peer-review

226 Scopus citations

Abstract

Background: Animal studies have demonstrated a burst of oxygen free radical generation after reperfusion of ischemic myocardium that could be blocked by administration of the free radical scavenger recombinant human superoxide dismutase (h-SOD). A multicenter, randomized, placebo-controlled clinical trial was designed to test the hypothesis that free radical-mediated reperfusion injury could be reduced by intravenous administration of h-SOD begun before percutaneous transluminal coronary angioplasty (PTCA) in patients with acute transmural myocardial infarction. Methods and Results: One hundred twenty patients were randomized to receive placebo (n=59) or h- SOD (n=61) given as a 10-mg/kg intravenous bolus followed by a 60-minute infusion of 0.2 mg · kg^-1 · min^-1. Left ventricular function was analyzed via paired contrast left ventriculograms performed before PTCA and after 6 to 10 days and paired radionuclide ventriculograms performed within 24 hours of PTCA and after 4 to 6 weeks. Both h-SOD- and placebo-treated patients showed improvement in global and regional left ventricular function after successful reperfusion. Compared with the placebo group, no additional improvement was observed in the patients treated with h-SOD. Conclusions: The results of this clinical trial failed to demonstrate a beneficial effect of h-SOD on global or regional left ventricular function in patients who underwent successful PTCA for treatment of acute myocardial infarction.

Original language	English (US)
Pages (from-to)	1982-1991
Number of pages	10
Journal	Circulation
Volume	89
Issue number	5
DOIs	https://doi.org/10.1161/01.CIR.89.5.1982
State	Published - May 1994
Externally published	Yes

Keywords

free radicals
myocardial infarction
reperfusion
superoxide dismutase

ASJC Scopus subject areas

Cardiology and Cardiovascular Medicine
Physiology (medical)

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10.1161/01.CIR.89.5.1982

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Flaherty, J. T., Pitt, B., Gruber, J. W., Heuser, R. R., Rothbaum, D. A., Burwell, L. R., George, B. S., Kereiakes, D. J., Deitchman, D., Gustafson, N., Brinker, J. A., Becker, L. C., Mancini, G. B. J., Topol, E., & Werns, S. W. (1994). Recombinant human superoxide dismutase (h-SOD) fails to improve recovery of ventricular function in patients undergoing coronary angioplasty for acute myocardial infarction. Circulation, 89(5), 1982-1991. https://doi.org/10.1161/01.CIR.89.5.1982

Flaherty, JT, Pitt, B, Gruber, JW, Heuser, RR, Rothbaum, DA, Burwell, LR, George, BS, Kereiakes, DJ, Deitchman, D, Gustafson, N, Brinker, JA, Becker, LC, Mancini, GBJ, Topol, E & Werns, SW 1994, 'Recombinant human superoxide dismutase (h-SOD) fails to improve recovery of ventricular function in patients undergoing coronary angioplasty for acute myocardial infarction', Circulation, vol. 89, no. 5, pp. 1982-1991. https://doi.org/10.1161/01.CIR.89.5.1982

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abstract = "Background: Animal studies have demonstrated a burst of oxygen free radical generation after reperfusion of ischemic myocardium that could be blocked by administration of the free radical scavenger recombinant human superoxide dismutase (h-SOD). A multicenter, randomized, placebo-controlled clinical trial was designed to test the hypothesis that free radical-mediated reperfusion injury could be reduced by intravenous administration of h-SOD begun before percutaneous transluminal coronary angioplasty (PTCA) in patients with acute transmural myocardial infarction. Methods and Results: One hundred twenty patients were randomized to receive placebo (n=59) or h- SOD (n=61) given as a 10-mg/kg intravenous bolus followed by a 60-minute infusion of 0.2 mg · kg-1 · min-1. Left ventricular function was analyzed via paired contrast left ventriculograms performed before PTCA and after 6 to 10 days and paired radionuclide ventriculograms performed within 24 hours of PTCA and after 4 to 6 weeks. Both h-SOD- and placebo-treated patients showed improvement in global and regional left ventricular function after successful reperfusion. Compared with the placebo group, no additional improvement was observed in the patients treated with h-SOD. Conclusions: The results of this clinical trial failed to demonstrate a beneficial effect of h-SOD on global or regional left ventricular function in patients who underwent successful PTCA for treatment of acute myocardial infarction.",

keywords = "free radicals, myocardial infarction, reperfusion, superoxide dismutase",

author = "Flaherty, {John T.} and Bertram Pitt and Gruber, {John W.} and Heuser, {Richard R.} and Rothbaum, {Donald A.} and Burwell, {Lawrence R.} and George, {Barry S.} and Kereiakes, {Dean J.} and David Deitchman and Nancy Gustafson and Brinker, {Jeffrey A.} and Becker, {Lewis C.} and Mancini, {G. B.John} and Eric Topol and Werns, {Steven W.}",

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doi = "10.1161/01.CIR.89.5.1982",

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T1 - Recombinant human superoxide dismutase (h-SOD) fails to improve recovery of ventricular function in patients undergoing coronary angioplasty for acute myocardial infarction

AU - Flaherty, John T.

AU - Pitt, Bertram

AU - Gruber, John W.

AU - Heuser, Richard R.

AU - Rothbaum, Donald A.

AU - Burwell, Lawrence R.

AU - George, Barry S.

AU - Kereiakes, Dean J.

AU - Deitchman, David

AU - Gustafson, Nancy

AU - Brinker, Jeffrey A.

AU - Becker, Lewis C.

AU - Mancini, G. B.John

AU - Topol, Eric

AU - Werns, Steven W.

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N2 - Background: Animal studies have demonstrated a burst of oxygen free radical generation after reperfusion of ischemic myocardium that could be blocked by administration of the free radical scavenger recombinant human superoxide dismutase (h-SOD). A multicenter, randomized, placebo-controlled clinical trial was designed to test the hypothesis that free radical-mediated reperfusion injury could be reduced by intravenous administration of h-SOD begun before percutaneous transluminal coronary angioplasty (PTCA) in patients with acute transmural myocardial infarction. Methods and Results: One hundred twenty patients were randomized to receive placebo (n=59) or h- SOD (n=61) given as a 10-mg/kg intravenous bolus followed by a 60-minute infusion of 0.2 mg · kg-1 · min-1. Left ventricular function was analyzed via paired contrast left ventriculograms performed before PTCA and after 6 to 10 days and paired radionuclide ventriculograms performed within 24 hours of PTCA and after 4 to 6 weeks. Both h-SOD- and placebo-treated patients showed improvement in global and regional left ventricular function after successful reperfusion. Compared with the placebo group, no additional improvement was observed in the patients treated with h-SOD. Conclusions: The results of this clinical trial failed to demonstrate a beneficial effect of h-SOD on global or regional left ventricular function in patients who underwent successful PTCA for treatment of acute myocardial infarction.

AB - Background: Animal studies have demonstrated a burst of oxygen free radical generation after reperfusion of ischemic myocardium that could be blocked by administration of the free radical scavenger recombinant human superoxide dismutase (h-SOD). A multicenter, randomized, placebo-controlled clinical trial was designed to test the hypothesis that free radical-mediated reperfusion injury could be reduced by intravenous administration of h-SOD begun before percutaneous transluminal coronary angioplasty (PTCA) in patients with acute transmural myocardial infarction. Methods and Results: One hundred twenty patients were randomized to receive placebo (n=59) or h- SOD (n=61) given as a 10-mg/kg intravenous bolus followed by a 60-minute infusion of 0.2 mg · kg-1 · min-1. Left ventricular function was analyzed via paired contrast left ventriculograms performed before PTCA and after 6 to 10 days and paired radionuclide ventriculograms performed within 24 hours of PTCA and after 4 to 6 weeks. Both h-SOD- and placebo-treated patients showed improvement in global and regional left ventricular function after successful reperfusion. Compared with the placebo group, no additional improvement was observed in the patients treated with h-SOD. Conclusions: The results of this clinical trial failed to demonstrate a beneficial effect of h-SOD on global or regional left ventricular function in patients who underwent successful PTCA for treatment of acute myocardial infarction.

KW - free radicals

KW - myocardial infarction

KW - reperfusion

KW - superoxide dismutase

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Recombinant human superoxide dismutase (h-SOD) fails to improve recovery of ventricular function in patients undergoing coronary angioplasty for acute myocardial infarction

Abstract

Keywords

ASJC Scopus subject areas

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