Cardiac release of cytokines and inflammatory responses in acute myocardial infarction.
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 beta 2-integrin Mac-1 (CD11b/CD18) and L-selectin (CD62L), and the cardiac release of thrombomodulin as a marker of endothelial injury.


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)-1 beta, IL-6, IL-8, tumor necrosis factor-alpha, 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 < or = .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 (-87 mean fl, P = .007) and with a thrombomodulin release (4.5 micrograms/L, P = .004). Transcardiac gradients in IL-1 beta and tumor necrosis factor-alpha 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.
Neumann
F J
FJ
Medizinische Klinik, Technischen Universität, München, Germany.
Ott
I
I
Gawaz
M
M
Richardt
G
G
Holzapfel
H
H
Jochum
M
M
Schömig
A
A
D000328:Adult; D000368:Aged; D015906:Angioplasty, Balloon, Coronary; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism*; D005260:Female; D006801:Humans; D019041:L-Selectin; D016177:Macrophage-1 Antigen / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000150:complications* / Q000378:metabolism* / Q000628:therapy; D009205:Myocarditis / Q000209:etiology*; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D009504:Neutrophils / Q000378:metabolism; D018180:Thrombomodulin / Q000378:metabolism
D015815:Cell Adhesion Molecules; D016207:Cytokines; D016177:Macrophage-1 Antigen; D018180:Thrombomodulin; D019041:L-Selectin