Author + information
- Received July 11, 1995
- Revision received September 20, 1995
- Accepted November 14, 1995
- Published online April 1, 1996.
- Masazumi Arai, MD,
- David J. Lefer, PhD,
- SO Takehiko, MD,
- Anthony Dipaula, BS,
- Thomas Aversano, MD and
- Lewis C. Becker, MD, FACC*
- ↵*Address for correspondence: Dr. Lewis C. Becker, The Johns Hopkins Hospital, 600 N. Wolfe Street, Halsted 500, Baltimore, Maryland 21287.
Objectives. This study investigated whether an antibody against neutrophil adhesion protein CD18 could limit myocardial infarct size and preserve left ventricular function after prolonged reperfusion in a canine model.
Background. Myocardial reperfusion injury is mediated in part by accumulation of activated neutrophils. Although antibodies against CD18 have been shown to reduce neutrophil influx and infarct size after ischemia and 3 to 4 h of reperfusion, it is unknown whether protection is sustained beyond this time or whether there is meaningful preservation of ventricular function.
Methods. Dogs undergoing 90-min circumflex coronary artery occlusion and 48-h reperfusion were randomized to receive 1 mg/kg bodyweight of R15.7 (an anti-CD18 antibody, n = 12) or saline (control, n = 12) 10 min before reperfusion. Contrast left ventriculography was used to measure left ventricular ejection fraction and regional chord shortening at baseline, during occlusion and at 48 h. Microspheres injected during occlusion were used to measure collateral flow and risk region size. Postmortem infarct size was measured with triphenyltetrazolium chloride.
Results. In the dose administered, R15.7 bound to neutrophils in vivo, with >85% saturation of CD18 for >24 h, with sustained antibody excess in the plasma. R15.7 significantly reduced infarct size after adjusting for the effect of collateral flow (p = 0.0002, analysis of covariance). In a subgroup of dogs with collateral flow <30% of nonischemic flow, infarct size was reduced from 34.6 ± 3.9% (mean ± SE) of the region at risk in the control group to 19.5 ± 3.3% in the antibody group (p = 0.008). Ejection fraction and regional chord shortening did not differ between the two groups at baseline or during occlusion, but after 48-h reperfusion, ejection fraction and inferior wall regional cord shortening (representing the infarct zone) were both higher in the R15.7 group than the control group (43.6 ± 2.9% vs. 28.5 ± 1.8%, p < 0.01; 2.55 ± 0.29% vs. 1.06 ± 0.18%, p < 0.05).
Conclusions. A single injection of an anti-CD18 antibody given before reperfusion can limit myocardial infarct size by nearly 50% and preserve global and regional left ventricular function after 48 h of reperfusion.
This study was supported by USPHS Grant 17655, Specialized Center of Research in Ischemic Heart Disease, from the National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland. Tables of hemodynamic and hematologic data are available on request.
- Received July 11, 1995.
- Revision received September 20, 1995.
- Accepted November 14, 1995.
- American College of Cardiology