Effects of External Counterpulsation on Plasma t-PA and PAI Activities and D-dimer Content in Patients with Acute Cerebral Infarction
Authors
Wang Jiansheng, Zhu Wenbing, Niu Jingzhong, Xu Jianmin, Shi Zhiying
Zhongshan Hospital, Shanghai Medical University, Shanghai, China
Source: usecp.com; Compiled and reviewed by Dr. Guoji Gong
Abstract
Objective: To investigate the effects of external counterpulsation (ECP) on the fibrinolytic system and thrombus formation in patients with acute cerebral infarction.
Methods: Enzyme-linked immunosorbent assay (ELISA) and colorimetric analysis were used to measure the changes in plasma tissue-type plasminogen activator (t-PA), plasminogen activator inhibitor (PAI) activity, and D-dimer levels before and after ECP in 20 patients with acute cerebral infarction and 10 non-infarction controls.
Results: After ECP treatment, t-PA activity increased in both the cerebral infarction and control groups, with a more pronounced increase in the control group; PAI activity remained unchanged in both groups; D-dimer content in the cerebral infarction group was slightly higher than that in the control group.
Conclusion: ECP treatment can increase plasma t-PA levels and enhance fibrinolytic activity in patients with cerebral infarction, which facilitates thrombus dissolution.
Keywords: ECP; t-PA; PAI; D-dimer
Materials and Methods
I. Study Population
Acute Cerebral Infarction Group: 20 patients with cerebral infarction in the internal carotid artery system (15 males, 5 females), aged 44–71 years (mean 57.6±7.8 years). All cases were diagnosed according to the criteria of the Second National Cerebrovascular Disease Academic Conference and confirmed by cranial CT or MRI.
Classification: 9 cases of small-focus infarction (max diameter ≤2 cm); 11 cases of large-focus infarction (max diameter >2 cm).
Treatment Timing: The interval from onset to ECP treatment ranged from 5 to 30 days (mean 14.9±6.79 days).
Control Group: 10 non-infarction patients (including cervical vertigo, Parkinson's disease, motor neuron disease, and tinnitus), consisting of 8 males and 2 females, aged 41–60 years (mean 55.3±6.41 years). Cranial CT or MRI confirmed the absence of cerebral infarction.
II. Research Methods
Materials: t-PA and PAI activity kits were provided by the Molecular Genetics Laboratory of Shanghai Medical University; D-dimer kits were provided by Shanghai Jiemen Biotechnology Co.
Equipment included a Heraeus low-speed refrigerated centrifuge (Switzerland), a 516mc microplate reader, and a WFB-V sequential positive pressure ECP device.
Specimen Preparation: Venous blood was collected after 10 minutes of rest and 1 hour after the first ECP session. Samples were mixed with 0.13 mol/L sodium citrate (9:1) and centrifuged at 3000 r/min for 10 minutes at 4°C.
Measurement: t-PA and D-dimer were measured via ELISA. PAI measurement followed a similar protocol to t-PA.
Results and Discussion
Before ECP, plasma t-PA activity in the infarction group was higher than in the control group (P<0.05). No inter-group differences were found for PAI or D-dimer (P>0.05).
Post-Treatment Changes
- t-PA Activity: Increased by 21.50% (P<0.05) in the infarction group and by 52.17% (P<0.01) in the control group.
- PAI Activity: No significant changes in either group.
- D-dimer Content: Increased by 76.47% (P<0.01) in the infarction group, while only increasing by 2.08% (P>0.05) in the control group.
Table 1. Comparison of t-PA, PAI, and D-dimer Levels Before and After ECP
| Group | n | Timing | t-PA (IU/mL) | PAI (AU/mL) | D-dimer (mg/mL) |
|---|---|---|---|---|---|
| Infarction | 20 | Pre-ECP | 2.00±0.71Δ | 8.42±0.21 | 0.68±0.52 |
| Post-ECP | 2.43±0.73∗ | 8.52±0.22 | 1.20±0.97∗∗ | ||
| Control | 10 | Pre-ECP | 1.38±0.57 | 8.47±0.29 | 0.48±0.29 |
| Post-ECP | 2.10±0.64∗∗ | 8.52±0.29 | 0.49±0.37 |
Note: ∗P<0.05, ∗∗P<0.01 (intra-group comparison); ΔP<0.05 (inter-group comparison).
Analysis by Infarction Type
Small-focus: t-PA increased by 26.94% (P<0.05), and D-dimer increased by 150.9% (P<0.05).
Large-focus: Showed no statistically significant increases in t-PA or D-dimer (P>0.05).
Table 2. t-PA, PAI, and D-dimer Changes: Small-focus vs. Large-focus Infarction
| Type | n | Timing | t-PA (IU/mL) | PAI (AU/mL) | D-dimer (mg/mL) |
|---|---|---|---|---|---|
| Small-focus | 9 | Pre-ECP | 1.93±0.71 | 8.43±0.33 | 0.55±0.33 |
| Post-ECP | 2.45±0.66∗ | 8.52±0.22 | 1.32±0.98∗ | ||
| Large-focus | 11 | Pre-ECP | 2.09±0.69 | 8.40±0.21 | 0.77±0.54 |
| Post-ECP | 2.20±0.79 | 8.52±0.20 | 0.98±0.79 |
Note: ∗P<0.05 (intra-group comparison).
Discussion
The results indicate that in patients with acute cerebral infarction, plasma t-PA activity undergoes a compensatory increase. ECP treatment further enhances this fibrinolytic activity significantly.
The marked increase in D-dimer levels following ECP—particularly in the infarction group and the small-focus subgroup—suggests an accelerated fibrinolytic process. This facilitates the dissolution of existing thrombi and potentially prevents the formation of new ones. Since PAI activity remained stable, it appears that ECP exerts its effect primarily by increasing t-PA release from the vascular endothelium via mechanical shear stress, rather than by inhibiting its inhibitors.
Furthermore, the data suggests that t-PA activity may be influenced by age (decreasing with age) and gender (slightly higher in males), though PAI activity appears independent of these factors in this study. In conclusion, ECP is an effective intervention for modulating the fibrinolytic system in acute stroke recovery.