Circulation, Vol 80, 1816-1827, Copyright © 1989 by American Heart Association
MR Litt, RW Jeremy, HF Weisman, JA Winkelstein and LC Becker
Reperfusion of ischemic myocardium may accelerate necrosis of injured
myocytes. To determine the role of neutrophil leukocytes in this process,
we examined whether neutrophil depletion during reperfusion could modify
infarct size in anesthetized dogs. The proximal circumflex coronary artery
was occluded for 90 minutes and then reperfused for 2 hours via an
extracorporeal circuit with either whole blood (n = 11) or with blood
depleted of neutrophils by leukocyte filters (n = 11). The leukocyte
filters caused near-total neutropenia in blood reperfusing the ischemic
myocardium (7 +/- 7 neutrophils/microliters compared with 2,551 +/-
317/microliters in controls, mean +/- SEM; p less than 0.001. Infarct size
was measured by planimetry of myocardial slices stained with
triphenyltetrazolium chloride (TTC), and the accuracy of TTC for
identifying necrotic myocardium was verified by electron microscopy. The
size of the ischemic risk region was the same in the control (41.6 +/-
1.0%) and neutropenic (41.8 +/- 2.1%) groups. Collateral blood flow to the
risk region was the same in control (0.15 +/- 0.03 ml/min/g) and
neutropenic (0.13 +/- 0.03 ml/min/g) groups. Among dogs with collateral
flow less than 0.2 ml/min/g, infarct size was reduced in the neutropenic
group (27.7 +/- 6.7% of risk region, n = 8), compared with control dogs
(52.5 +/- 5.7%; n = 7; p = 0.02). Multiple linear regression described the
relation between infarct size, risk region size, and collateral flow in the
control group, and the same regression relation was used to predict infarct
size for the neutropenic group. Mean predicted infarct size in the
neutropenic group (n = 11) was 16.8 +/- 3.4% of left ventricle, whereas
mean observed infarct size was 9.6 +/- 3.1% (p less than 0.01). The extent
of the no-reflow zone (absence of thioflavin-S-fluorescence) was also less
in the neutropenic than the control group (2.2 +/- 0.8% vs. 8.1 +/- 2.7% of
the risk region, p less than 0.05). Neutropenia limited to the reperfusion
period is associated with significant reductions in the extent of the
infarct and no-reflow zones after 90 minutes of ischemia. These findings
support the hypothesis that reperfusion necrosis occurs after prolonged
myocardial ischemia and indicate that neutrophil leukocytes are important
mediators of such reperfusion injury.
ARTICLES
Neutrophil depletion limited to reperfusion reduces myocardial infarct size after 90 minutes of ischemia. Evidence for neutrophil-mediated reperfusion injury
Department of Medicine, Johns Hopkins Medical Institutions, Baltimore, MD 21205.
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