Glucocorticoid treatment prevents progressive myocardial dysfunction resulting from experimental coronary microembolization.
BACKGROUND
The frequency and importance of microembolization in patients with acute coronary syndromes and during coronary interventions have recently been appreciated. Experimental microembolization induces immediate ischemic dysfunction, which recovers within minutes. Subsequently, progressive contractile dysfunction develops over several hours and is not associated with reduced regional myocardial blood flow (perfusion-contraction mismatch) but rather with a local inflammatory reaction. We have now studied the effect of antiinflammatory glucocorticoid treatment on this progressive contractile dysfunction.


RESULTS
Microembolization was induced by injecting microspheres (42-microm diameter) into the left circumflex coronary artery. Anesthetized dogs were followed up for 8 hours and received placebo (n=7) or methylprednisolone 30 mg/kg IV either 30 minutes before (n=7) or 30 minutes after (n=5) microembolization. In addition, chronically instrumented dogs received either placebo (n=4) or methylprednisolone (n=4) 30 minutes after microembolization and were followed up for 1 week. In acute placebo dogs, posterior systolic wall thickening was decreased from 20.0+/-2.1% (mean+/-SEM) at baseline to 5.8+/-0.6% at 8 hours after microembolization. Methylprednisolone prevented the progressive myocardial dysfunction. Increased leukocyte infiltration in the embolized myocardium was prevented only when methylprednisolone was given before microembolization. In chronic placebo dogs, progressive dysfunction recovered from 5.0+/-0.7% at 4 to 6 hours after microembolization back to baseline (19.1+/-1.6%) within 5 days. Again, methylprednisolone prevented the progressive myocardial dysfunction.


CONCLUSIONS
Methylprednisolone, even when given after microembolization, prevents progressive contractile dysfunction.
Skyschally
Andreas
A
Institut für Pathophysiologie, Zentrum für Innere Medizin, Universitätsklinikum Essen, Essen, Federal Republic of Germany.
Haude
Michael
M
Dörge
Hilmar
H
Thielmann
Matthias
M
Duschin
Alexej
A
van de Sand
Anita
A
Konietzka
Ina
I
Büchert
Astrid
A
Aker
Stephanie
S
Massoudy
Parwis
P
Schulz
Rainer
R
Erbel
Raimund
R
Heusch
Gerd
G
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D003326:Coronary Circulation; D003327:Coronary Disease / Q000188:drug therapy* / Q000209:etiology; D003331:Coronary Vessels; D004285:Dogs; D006334:Heart Function Tests; D006439:Hemodynamics; D007269:Injections, Intra-Arterial; D008775:Methylprednisolone / Q000627:therapeutic use*; D008863:Microspheres; D009200:Myocardial Contraction / Q000187:drug effects*; D017202:Myocardial Ischemia / Q000188:drug therapy / Q000209:etiology; D009205:Myocarditis / Q000188:drug therapy* / Q000209:etiology; D009206:Myocardium / Q000737:chemistry / Q000473:pathology; D011292:Premedication; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D000893:Anti-Inflammatory Agents; D014409:Tumor Necrosis Factor-alpha; D008775:Methylprednisolone