Gurbel P A, Anderson R D, MacCord C S, Scott H, Komjathy S F, Poulton J, Stafford J L, Godard J
University of Maryland Medical Center, Department of Medicine, Baltimore 21201.
Circulation. 1994 Jan;89(1):361-5. doi: 10.1161/01.cir.89.1.361.
The early establishment of infarct artery reperfusion by intravenous thrombolytic therapy has improved survival after acute myocardial infarction. Investigations of reperfusion have focused on the effects of specific thrombolytic agents, anticoagulation, and platelet inhibition. However, little attention has been given to the relation of arterial blood pressure to thrombolysis, a factor that probably affects thrombolytic agent delivery to the obstructing thrombus.
The effect of arterial diastolic pressure augmentation by intra-aortic balloon counterpulsation (IABP) on reperfusion after intravenous thrombolytic therapy was studied in a canine model. A critical left anterior descending coronary artery stenosis was created by an occluder. Acute thrombosis immediately proximal to the occluder was formed by local injection of a blood and thrombin mixture into a segment of the artery that had intimal damage (groups 1 through 3). Continuous coronary blood flow velocity was measured by an epicardial Doppler probe. Group 1 (n = 7) served as control. Group 2 (n = 6) received an intravenous, front-loaded recombinant tissue-type plasminogen activator (rTPA) regimen (1.25 mg/kg total dose, 15% as bolus, 50% in the first 30 minutes, and 35% for the following 60 minutes). Group 3 (n = 6) received the same rTPA regimen with IABP beginning at the start of rTPA administration. Coronary blood flow velocity, arterial pressure, and heart rate were observed for 150 minutes after the start of thrombolytic therapy. Five animals did not undergo coronary thrombosis (group 4) and had coronary blood flow velocity determined before and after IABP at baseline and after creation of critical stenosis. Mean systolic arterial blood pressure and heart rate were not statistically different between groups. Peak augmented diastolic pressure by IABP was 97.9 +/- 1.3% of systolic pressure in group 3 dogs. Spontaneous reperfusion did not occur in any group 1 dogs. All animals treated with rTPA reperfused. Reperfusion occurred in group 3 (13.1 +/- 2.1 minutes) earlier than in group 2 (39.2 +/- 9.4 minutes, P = .02). Overall duration of arterial patency did not differ between group 2 (81.4 +/- 16.6 minutes) and group 3 (94.9 +/- 15.3 minutes, P = .52). Reocclusions occurred with similar frequency (P = .85) in groups 2 and 3. In group 4, IABP did not increase baseline coronary blood flow velocity.
This study demonstrates that augmentation of diastolic arterial pressure by IABP enhances thrombolysis, leading to faster reperfusion. This effect appears to be unrelated to an increase in coronary blood flow and may be due to an effect of the augmented diastolic blood pressure wave on the obstructing thrombus. These findings suggest that the time to reperfusion by rTPA may be blood pressure dependent. The relation of arterial blood pressure to successful thrombolysis may have important implications for future treatment strategies for myocardial infarction.
通过静脉溶栓疗法尽早实现梗死动脉再灌注可提高急性心肌梗死后的生存率。再灌注研究主要集中在特定溶栓药物、抗凝及血小板抑制的作用上。然而，动脉血压与溶栓的关系却很少受到关注，而这一因素可能会影响溶栓药物向阻塞血栓的输送。
在犬模型中研究了主动脉内球囊反搏（IABP）增加动脉舒张压对静脉溶栓治疗后再灌注的影响。用封堵器造成左前降支冠状动脉严重狭窄。通过向一段有内膜损伤的动脉局部注射血液和凝血酶混合物，在封堵器近端立即形成急性血栓（第1至3组）。用体表多普勒探头测量冠状动脉血流速度。第1组（n = 7）作为对照。第2组（n = 6）接受静脉负荷剂量重组组织型纤溶酶原激活剂（rTPA）方案（总剂量1.25 mg/kg，15%为推注剂量，50%在最初30分钟内给予，35%在接下来60分钟内给予）。第3组（n = 6）在开始给予rTPA时即开始IABP，并接受相同的rTPA方案。溶栓治疗开始后150分钟观察冠状动脉血流速度、动脉压和心率。5只动物未发生冠状动脉血栓形成（第4组），并在基线及造成严重狭窄后测定IABP前后的冠状动脉血流速度。各组间平均收缩动脉血压和心率无统计学差异。第3组犬IABP使舒张期压力峰值增加至收缩压的97.9±1.3%。第1组犬均未发生自发再灌注。所有接受rTPA治疗的动物均实现再灌注。第3组再灌注发生时间（13.1±2.1分钟）早于第2组（39.2±9.4分钟，P = 0.02）。第2组（81.4±16.6分钟）和第3组（94.9±15.3分钟，P = 0.52）动脉通畅的总持续时间无差异。第2组和第3组再闭塞发生率相似（P = 0.85）。在第4组，IABP未增加基线冠状动脉血流速度。
本研究表明，IABP增加舒张期动脉压可增强溶栓效果，使再灌注更快。这种作用似乎与冠状动脉血流增加无关，可能是由于舒张期血压波增强对阻塞血栓的作用。这些发现提示，rTPA实现再灌注的时间可能取决于血压。动脉血压与成功溶栓的关系可能对未来心肌梗死治疗策略具有重要意义。
