Baardman T, Hermens W T, Lenderink T, Molhoek G P, Grollier G, Pfisterer M, Simoons M L
Thoraxcenter, Erasmus University Rotterdam, The Netherlands.
Eur Heart J. 1996 Feb;17(2):237-46. doi: 10.1093/oxfordjournals.eurheartj.a014840.
The recent international GUSTO trial of 41,021 patients with acute myocardial infarction demonstrated improved 90-min infarct related artery patency as well as reduced mortality in patients treated with an accelerated regimen of tissue plasminogen activator, compared to patients treated with streptokinase. A regimen combining tissue plasminogen activator and streptokinase yielded intermediate results. The present study investigated the effects of treatment on infarct size and enzyme release kinetics in a subgroup of these patients.
A total of 553 patients from 15 hospitals were enrolled in the study. Four thrombolytic strategies were compared: streptokinase with subcutaneous heparin, streptokinase with intravenous (i.v.) heparin, tissue plasminogen activator with i.v. heparin, and streptokinase plus tissue plasminogen activator with i.v. heparin. The activity of alpha-hydroxybutyrate dehydrogenase (HBDH) in plasma was centrally analysed and infarct size was defined as cumulative HBDH release per litre of plasma within 72 h of the first symptoms (Q(72)). Patency of the infarct-related vessel was determined by angiography in 159 patients, 90 min after treatment.
Infarct size was 3.72 g-eq.1(-1) in patients with adequate coronary perfusion (TIMI-3) at the 90 min angiogram and larger in patients with TIMI-2 (4.35 g-eq.1(-1) or TIMI 0-1 (5.07 g-eq.1(-1) flow (P = 0.024). In this subset of the GUSTO angiographic study, early coronary patency rates (TIMI 2 + 3) were similar in the two streptokinase groups (53 and 46%). Higher, but similar, patency rates were observed in the tissue plasminogen activator and combination therapy groups (87 and 90%). Median infarct size for the four treatment groups, expressed in gram-equivalents (g-eq) of myocardium, was 4.4, 4.5, 3.9 and 3.9 g-eq per litre of plasma (P = 0.04 for streptokinase vs tissue plasminogen activator). Six hours after the first symptoms, respectively 5.3, 6.6, 14.0 and 13.6% of total HBDH release was complete (P < 0.0001 for streptokinase vs tissue plasminogen activator).
Rapid and complete coronary reperfusion salvages myocardial tissue, resulting in limitation of infarct size and accelerated release of proteins from the myocardium. Treatment with tissue plasminogen activator, resulting in earlier reperfusion was more effective in reducing infarct size than the streptokinase regimens, which contributes to the differences in survival between treatment groups in the GUSTO trial.
近期一项针对41021例急性心肌梗死患者的国际GUSTO试验表明，与接受链激酶治疗的患者相比，接受加速给药方案组织型纤溶酶原激活剂治疗的患者梗死相关动脉在90分钟时的通畅率有所提高，死亡率也有所降低。组织型纤溶酶原激活剂与链激酶联合使用的方案产生了中等效果。本研究调查了这些患者亚组中治疗对梗死面积和酶释放动力学的影响。
来自15家医院的553例患者纳入本研究。比较了四种溶栓策略：链激酶联合皮下肝素、链激酶联合静脉注射肝素、组织型纤溶酶原激活剂联合静脉注射肝素、链激酶加组织型纤溶酶原激活剂联合静脉注射肝素。对血浆中α-羟丁酸脱氢酶（HBDH）活性进行集中分析，梗死面积定义为首次出现症状后72小时内每升血浆中HBDH的累积释放量（Q(72)）。159例患者在治疗90分钟后通过血管造影确定梗死相关血管的通畅情况。
在90分钟血管造影显示冠状动脉灌注良好（TIMI-3）的患者中，梗死面积为3.72克当量/升，在TIMI-2（4.35克当量/升）或TIMI 0-1（5.07克当量/升）血流的患者中梗死面积更大（P = 0.024）。在GUSTO血管造影研究的这一亚组中，两个链激酶组的早期冠状动脉通畅率（TIMI 2 + 3）相似（分别为53%和46%）。在组织型纤溶酶原激活剂组和联合治疗组中观察到更高但相似的通畅率（分别为87%和90%）。四个治疗组以心肌克当量（g-eq）表示的梗死面积中位数分别为每升血浆4.4、4.5、3.9和3.9克当量（链激酶与组织型纤溶酶原激活剂相比，P = 0.04）。首次出现症状6小时后，总HBDH释放量分别完成了5.3%、6.6%、14.0%和13.6%（链激酶与组织型纤溶酶原激活剂相比，P < 0.0001）。
快速而完全的冠状动脉再灌注可挽救心肌组织，从而限制梗死面积并加速心肌蛋白释放。组织型纤溶酶原激活剂治疗导致再灌注更早，在减少梗死面积方面比链激酶方案更有效，这有助于解释GUSTO试验中各治疗组生存率的差异。
