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(Circulation. 1995;92:748-755.)
© 1995 American Heart Association, Inc.
Articles |
From the Medizinische Klinik der Technischen Universität and the Abteilung Klinische Chemie und Klinische Biochemie an der Chirurgischen Innenstadtklinik der Ludwig-Maximilians-Universität (M.J.), München, Germany.
Correspondence to Priv-Doz Dr Franz-Josef Neumann, Medizinische Klinik der Technischen Universität, Ismaninger Str 22, 81675 München, Germany. E-mail neumann@med1.med.tu-muenchen.de.
Background In animal models of myocardial infarction (MI), inflammatory responses compromise microcirculation during reperfusion and restrict functional recovery. To investigate cardiac inflammatory responses in patients with acute MI, we examined the cardiac release of cytokines, the expression on neutrophils of the ß2-integrin Mac-1 (CD11b/CD18) and L-selectin (CD62L), and the cardiac release of thrombomodulin as a marker of endothelial injury.
Methods and Results In 12 patients with acute anterior MI, blood
samples were obtained from the coronary sinus and from the
aorta immediately before and after recanalization
of the coronary occlusion by balloon angioplasty. Twelve
patients undergoing elective balloon angioplasty served as control
subjects. Plasma concentrations of interleukin (IL)-1ß, IL-6, IL-8,
tumor necrosis factor-
, and thrombomodulin were determined by
immunoassay, and surface expression of CD11b and CD62L was assessed by
flow cytometry. Differences in coronary sinus and
arterial blood were found in IL-6 before (median, 6.3 ng/L,
P=.01) and after (13.4 ng/L, P=.002)
recanalization and in IL-8 after
recanalization (10.7 ng/L, P=.02). The
cardiac release of both cytokines significantly
(P
.03) increased with reperfusion. Cytokine
release after reperfusion was associated with significant transcardiac
gradients in surface expression on neutrophils of CD11b (10.1 mean
channel of fluorescence intensity [mean fl], P=.01)
and
CD62L (-8.7 mean fl, P=.007) and with a thrombomodulin
release (4.5 µg/L, P=.004). Transcardiac gradients in
IL-1ß and tumor necrosis factor-
were not found. None of the
changes found in MI were detectable in the control group.
Conclusions As evidence of cardiac inflammatory responses in reperfused acute MI, the study demonstrates cardiac neutrophil activation with signs of endothelial injury and a release of the proinflammatory cytokines IL-8 and IL-6. These findings may assist in the design of pharmacological interventions aimed at reducing microvascular reperfusion injury.
Key Words: myocardial infarction endothelium leukocytes reperfusion cytokines
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