Skyschally Andreas, Haude Michael, Dörge Hilmar, Thielmann Matthias, Duschin Alexej, van de Sand Anita, Konietzka Ina, Büchert Astrid, Aker Stephanie, Massoudy Parwis, Schulz Rainer, Erbel Raimund, Heusch Gerd
Institut für Pathophysiologie, Zentrum für Innere Medizin, Universitätsklinikum Essen, Essen, Federal Republic of Germany.
Circulation. 2004 May 18;109(19):2337-42. doi: 10.1161/01.CIR.0000127961.66744.F4. Epub 2004 Apr 26.
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.
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.
Methylprednisolone, even when given after microembolization, prevents progressive contractile dysfunction.
急性冠脉综合征患者及冠状动脉介入治疗过程中微栓塞的发生率和重要性近来已得到重视。实验性微栓塞可诱发即刻缺血性功能障碍,数分钟内即可恢复。随后,数小时内会逐渐出现进行性收缩功能障碍,且与局部心肌血流减少(灌注-收缩不匹配)无关,而是与局部炎症反应有关。我们现在研究了抗炎糖皮质激素治疗对这种进行性收缩功能障碍的影响。
通过向左回旋支冠状动脉注射微球(直径42微米)诱导微栓塞。对麻醉犬进行8小时随访,在微栓塞前30分钟(n = 7)或微栓塞后30分钟(n = 5)给予安慰剂(n = 7)或30毫克/千克静脉注射甲泼尼龙。此外,长期植入仪器的犬在微栓塞后30分钟接受安慰剂(n = 4)或甲泼尼龙(n = 4),并随访1周。在急性给予安慰剂的犬中,微栓塞后8小时后壁收缩期增厚从基线时的20.0±2.1%(平均值±标准误)降至5.8±0.6%。甲泼尼龙可预防进行性心肌功能障碍。仅在微栓塞前给予甲泼尼龙时,可预防栓塞心肌中白细胞浸润增加。在慢性给予安慰剂的犬中,微栓塞后4至6小时进行性功能障碍从5.0±0.7%在5天内恢复至基线水平(19.1±1.6%)。同样,甲泼尼龙可预防进行性心肌功能障碍。
即使在微栓塞后给予甲泼尼龙,也可预防进行性收缩功能障碍。