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Integrative Physiology |
in Coronary Microembolization
From the Institute of Pathophysiology (A.S., P.G., S.H., R.S., G.H.) and Department of Cardiology (R.E.), Center of Internal Medicine, University of Essen Medical School; and Lukaskrankenhaus (M.H.), Neuss, Germany.
Correspondence to Prof Dr Gerd Heusch, Institut für Pathophysiologie, Zentrum für Innere Medizin, Universitätsklinikum Essen, Hufelandstraße 55, 45122 Essen, Germany. E-mail gerd.heusch{at}uk-essen.de
In patients with unstable angina, plaque rupture and coronary microembolization (ME) can precede complete coronary artery occlusion and impending infarction. ME-induced microinfarcts initiate an inflammatory reaction with increased tumor necrosis factor-
(TNF-
) expression, resulting in progressive contractile dysfunction. However, TNF-
is not only a negative inotrope but can also protect the myocardium against infarction. In anesthetized pigs, we studied whether ME protects against infarction when TNF-
expression is increased. ME (group1; n=7) was induced by intracoronary infusion of microspheres (42 µm; 3000 per mL/min inflow). Controls (group 2; n=8) received saline. Groups 3 and 4 (n=4 each) were pretreated with ovine TNF-
antibodies (25 mg/kg body weight) 30 minutes before ME or placebo, respectively. Ischemia (90 minutes) was induced 6 hours after ME when TNF-
was increased (66±21 pg/g wet weight; mean±SEM) or after placebo (TNF-
, 21±10 pg/g; P<0.05). Infarct size (percentage area at risk) was determined after 2 hours of reperfusion (triphenyl tetrazolium chloride staining). ME decreased systolic wall thickening progressively over 6 hours (group 1 versus group 2, 65±4% versus 90±1%; percentage of baseline; P<0.05). TNF-
antibodies attenuated the progressive decrease in systolic wall thickening following ME (group 3, 77±5% of baseline; P<0.05 versus group 1) with no effect in controls (group 4; 90±8% of baseline). With ME, infarct size was decreased to 18±4% versus 33±4% in group 2 (P<0.05). The infarct size reduction was abolished by TNF-
antibodies (group 3 versus group 4, 29±3% versus 35±5%). In ME, TNF-
is responsible for both progressive contractile dysfunction and delayed protection against infarction.
Key Words: microembolization inflammation myocardial infarction TNF-
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