Effects of Enhanced External Counterpulsation on Plasma Endothelin, Renin, and Angiotensin II in Patients with Ischemic Stroke
Authors
Zhao Guanlin, Wu Yilin
Shanghai Friendship Hospital, Shanghai, China
Source: usecp.com (Compiled and reviewed by Gong Guoji)
Abstract
Background: Reports suggest that plasma endothelin (ET), renin, and angiotensin II (Ang II) levels are elevated during acute ischemic stroke and correlate with disease severity. While Enhanced External Counterpulsation (ECP) is recommended for treating acute ischemic stroke, whether its efficacy is related to changes in these plasma markers remains to be confirmed.
Objective: To observe the changes in plasma ET, renin, and Ang II before and after ECP in 13 patients with acute ischemic stroke and to explore the underlying therapeutic mechanisms.
Conclusion: ECP significantly reduces plasma ET levels (P < 0.05), suggesting that ECP may improve endothelial cell function in stroke patients.
I. Subjects and Methods
1. Study Participants
The study included 13 patients with acute ischemic stroke (9 females, 4 males) with a mean age of 60.38 years. All participants had a history of hypertension and a left ventricular ejection fraction (LVEF) > 51%. Three cases were complicated by coronary heart disease.
2. Treatment and Measurement
ECP treatment was initiated upon admission. Plasma levels of endothelin, renin, and angiotensin I were measured using radioimmunoassay before the start of treatment and after the completion of the course. Statistical analysis was performed to evaluate the changes.
II. Results
The changes in plasma endothelin, renin, and angiotensin I levels before and after ECP are summarized in Tables 1–3.
Table 1. Changes in Plasma Endothelin Before and After ECP
| Case No. | Pre-ECP (pg/mL) | Post-ECP (pg/mL) |
|---|---|---|
| 1 | 88.9 | 88.0 |
| 2 | 89.5 | 40.0 |
| 3 | 105.5 | 67.6 |
| 4 | 73.0 | 52.8 |
| 5 | 36.1 | 10.0 |
| 6 | 65.7 | 133.8 |
| 7 | 122.1 | 97.9 |
| 8 | 132.1 | 130.9 |
| 9 | 93.0 | 56.8 |
| 10 | 140.6 | 52.0 |
| 11 | 113.9 | 71.1 |
| 12 | 60.4 | 34.7 |
| 13 | 31.4 | 10.0 |
Statistical Results: t = 2.401124, P < 0.05.
Analysis: Before ECP, plasma ET was elevated in 11 out of 13 patients. After ECP, ET levels decreased in 12 patients, with 5 returning to the normal range. The difference was statistically significant.
Table 2. Changes in Plasma Renin Before and After ECP
| Case No. | Pre-ECP (ng/mL) | Post-ECP (ng/mL) |
|---|---|---|
| 1 | 0.15 | 0.02 |
| 2 | 1.82 | 2.88 |
| 3 | 2.45 | 1.21 |
| 4 | 5.01 | 3.65 |
| 5 | 5.6 | 5.35 |
| 6 | 7.4 | 4.77 |
| 7 | 7.53 | 0.1 |
| 8 | 6.03 | 1.5 |
| 9 | 28.66 | 18.0 |
| 10 | 0.7 | 4.17 |
| 11 | 0.1 | 6.3 |
| 12 | 0.1 | 0.55 |
| 13 | 0.53 | 0.36 |
Statistical Results: t = 1.093834, P > 0.05.
Analysis: Before ECP, renin was elevated in only 6 cases. After ECP, levels decreased in 9 out of 13 cases; however, the difference was not statistically significant.
Table 3. Changes in Serum Angiotensin I Before and After ECP
| Case No. | Pre-ECP (pg/mL) | Post-ECP (pg/mL) |
|---|---|---|
| 1 | 52.2 | 10.0 |
| 2 | 20.0 | 154.5 |
| 3 | 93.3 | 52.8 |
| 4 | 124.2 | 36.4 |
| 5 | 115.2 | 131.3 |
| 6 | 445.1 | 127.3 |
| 7 | 292.0 | 108.6 |
| 8 | 51.0 | 33.4 |
| 9 | 60.9 | 49.0 |
| 10 | 59.2 | 64.9 |
| 11 | 20.0 | 103.9 |
| 12 | 43.2 | 60.9 |
| 13 | 56.6 | 50.2 |
Statistical Results: t = 1.0923896, P > 0.05.
Analysis: Before ECP, Ang I was elevated in 5 cases. After ECP, levels decreased in 9 out of 13 cases, but the difference was not statistically significant.
III. Discussion
Endothelin (ET) is a biologically active polypeptide produced by vascular endothelial cells and is the most potent vasoconstrictor known to date. Tissue ischemia, hypoxia, and lipid peroxidation damage stimulate the synthesis and release of ET, which in turn activates the Renin-Angiotensin-Aldosterone System (RAAS), leading to increased renin and Ang II levels.
In this study of 13 acute ischemic stroke patients, plasma ET was significantly elevated in 84.6% of cases before ECP. However, renin was elevated in only 6 cases, and Ang I in only 5 cases. This suggests that while ET is markedly increased in ischemic stroke, renin and Ang II may not always be elevated. This may be because hypertensive patients can present with low-renin or normal-renin profiles. Furthermore, while some studies suggest ET increases renin activity, others have found the opposite. Additionally, the preserved LVEF (mean > 51%) in these patients suggests that RAAS activation via heart failure was not a primary factor.
Therapeutic Mechanism of ECP
After ECP, 12 out of 13 patients showed a significant decrease in ET (P < 0.05). This indicates that ECP works by:
- Increasing cerebral blood flow and improving tissue oxygenation.
- Reducing oxygen free radical formation and inhibiting peroxidative damage.
- Decreasing the synthesis and release of ET by endothelial cells.
Therefore, ECP may play a role in improving vascular endothelial cell function. The lack of a statistically significant effect on renin and Ang II in this study may be due to the small sample size and warrants further verification in larger cohorts.