Relationship of Plasminogen Activator Inhibitor-1 Levels following Thrombolytic Therapy with rt-PA as Compared to Streptokinase and Patency of Infarct Related Coronary Artery

Abstract

Summary Background: Type 1 plasminogen activator inhibitor (PAI-1) is considered to be risk factor for acute myocardial infarction (AMI). A rebound of circulating PAI-1 has been reported after rt-PA administration. We investigated the relationships between PAI-1 levels before and after thrombolytic therapy with streptokinase (SK) as compared to rt-PA and the patency of infarct-related arteries. Methods and Results: Fifty five consecutive patients with acute MI were randomized to strep-tokinase or rt-PA. The plasma PAI-1 levels were studied before and serially within 24 h after thrombolytic administration. Vessel patency was assessed by an angiogram at 5 ± 1days. The PAI-1 levels increased significantly with both rt-PA and SK as shown by the levels obtained from a control group of 10 patients treated with coronary angioplasty alone. However, the area under the PAI-1 curve was significantly higher with SK than with rt-PA (p <0.01) and the plasma PAI-1 levels peaked later with SK than with rt-PA (18 h versus 3 h respectively). Conversely to PAI-1 levels on admission, the PAI-1 levels after thrombolysis were related to vessel patency. Plasma PAI-1 levels 6 and 18 h after SK therapy and the area under the PAI-1 curve were significantly higher in patients with occluded arteries (p <0.002, p <0.04 and p <0.05 respectively).The same tendency was observed in the t-PA group without reaching significance. Conclusions: This study showed that the PAI-1 level increase is more pronounced after SK treatment than after t-PA treatment. There is a relationship between increased PAI-1 levels after thrombolytic therapy and poor patency. Therapeutic approaches aimed at quenching PAI-1 activity after thrombolysis might be of interest to improve the efficacy of thrombolytic therapy for acute myocardial infarction.

Adiponectin and Metabolic Syndrome

“…Circulating PAI-1 has been considered to be a strong risk factor of coronary artery disease. 14 These data suggest that the secreted PAI-1 from accumulated visceral fat may contribute to the determination of plasma PAI-1 levels, and increased secretion of PAI-1 from accumulated visceral adipose tissue may have an important role in the development of thrombotic disorders and atherosclerosis frequently found in obesity, especially visceral obesity.…”

Effects of Recombinant Tissue Plasminogen Activator After Intraluminal Thread Occlusion in Mice: Role of Hemodynamic Alterations

“…26 Additionally, it has been shown that administration of rtPA may lead to the activation of plasminogen activator inhibitor-1, thereby also resulting in inhibition of endogenous fibrinolysis. 27 It is noteworthy that the effects of rtPA depended on the application time of rtPA. In contrast to animals treated during reperfusion, a slight but nonsignificant reduction of infarct size was noted in animals receiving rtPA infusions during MCA occlusion.…”

Accelerated plasminogen activator inhibitor may prevent late restenosis after coronary stenting in acute myocardial infarction

“…Strauss et al 15 also demonstrated that plasma PAI-1 levels were lower in the restenosis group than in the nonrestenosis group at both preangioplasty and postangioplasty time points. Regarding AMI, evidence that plasma PAI-1 levels increased after emergent coronary angioplasty has been demonstrated, 4,5 but the relationship between increased PAI-1 and restenosis has not been elucidated. There are several hypotheses as to how plasma PAI-1 reflects the ongoing process of restenosis.…”

“…Several investigators demonstrated an increase in plasma PAI-1 levels after emergent PCI in AMI. 4,5 However, its pathophysiologic significance is still unknown. On the other hand, the kinetics of PAI-1 levels after elective PCI in stable angina are controversial, and the pathophysiologic role of PAI-1 in the development of restenosis has not been established.…”