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(Stroke. 1998;29:1257-1258.)
© 1998 American Heart Association, Inc.

Letters to the Editor

Endothelins in Acute Ischemic Stroke

Dr Gerhard F. Hamann, PD

Department of Neurology, Ludwig-Maximilians-University, Klinikum Großhadern, Munich, Germany

To the Editor:

I read with interest the recently published article by Lampl et al.¹ Because we have also investigated the role of endothelin in acute cerebrovascular accidents, some comments on their data may highlight the problematic role of the endothelins in acute stroke patients.

Lampl et al emphasize the role of an elevation of cerebrospinal fluid (CSF) endothelin-1 (ET-1), whereas the plasma values did not show any significant changes. In their 1992 article,² the same author group demonstrated a relevance of ET-1 plasma levels. There was a 4-fold increase in the plasma ET-1, especially during the first 24 hours after stroke. The authors do not offer an explanation for these somewhat contradictory results. They offer the very early time point of the measurement in their recent study compared with previous findings. However, in their 1992 study² the early patients actually had the highest ET-1 plasma levels. The other offered explanation—that the plasma ET-1 level in the control group was extremely high, thus preventing statistically significant results for the plasma ET-1 levels—is a problem that is very difficult to handle. It is obvious that the control group in the 1997 study has a mean plasma ET-1 level 2-fold higher than those in 1992, but this major difference may only emphasize the extreme variability of the measurement or variability between healthy controls. Actually, one may argue that the results in the 1992 study were less significant or even not significant compared with those in the 1997 control group.

Our own group published results concerning big endothelin-1 (BET-1), the precursor of ET-1, in acute ischemic stroke.³ There was no overall elevation in plasma BET-1. Differences between patients with larger or smaller infarctions may reflect more an indicator function for the amount of damaged brain than a pathophysiological role.³

The authors claimed to be the first to report CSF ET-1 levels in acute ischemic stroke. However, in 1990 Suzuki et al⁴ described 2 patients with acute ischemic stroke who had already CSF ET-1 determination. This group did not find any elevation of ET-1 in CSF after acute stroke. They even used these 2 patients as controls for elevated ET-1 CSF samples from patients with SAH. Interestingly, Lampl et al¹ cited another work of Suzuki et al⁵ twice (as references 18 and 32) in their 1997 paper but failed to refer to the study with the CSF ET-1 values in 2 stroke patients.

The authors cited our own article⁶ from 1994 incorrectly. This study showed no significant changes in BET-1 in patients suffering from acute intracerebral hemorrhage. The authors cited this paper in such a way that the reader may think it has shown elevated ET-1 in acute subarachnoid hemorrhage.

Considering all the different studies together,^{1 2 3 4 5 6} it might be more appropriate to conclude that there is no consistent pattern of endothelin elevation after acute ischemic stroke. Increased levels of ET-1 may reflect the degree of tissue damage rather than a pathophysiological role. This may also be discussed in subarachnoid hemorrhage.⁷ One may obviously suspect a possible deleterious role of ET-1 in acute ischemic stroke, because the constrictive mode in vasoregulation is mediated by ET-1. However, the data from clinical studies from which one may draw conclusions are too weak to establish the experimentally proposed relationship between endothelin elevation and secondary vasoconstriction/ischemia in acute stroke patients.

References

1. Lampl Y, Fleminger G, Gilad R, Galron R, Savora-Pinhas I, Sokolovsky M. Endothelin in cerebrospinal fluid and plasma of patients in the early stage of ischemic stroke. Stroke. 1997;28:1951–1955.[Abstract/Free Full Text]

2. Ziv I, Fleminger G, Dyaldetti R, Achiron A, Melamed E, Sokolovsky M. Increased plasma endothelin 1 in acute stroke. Stroke. 1992;23:1014–1016.[Abstract/Free Full Text]

3. Hamann GF, Isenberg E, Strittmatter M, Moili R, Schimrigk K. Big-endothelin in acute ischemic stroke. J Stroke Cerebrovasc Dis. 1993;3:256–260.

4. Suzuki H, Sato S, Suzuki Y, Oka M, Tsuchiya T, Iino I, Yamanaka T, Isgihara N, Shimoda S. Endothelin immunoreactivity in CSF of patients with subarachnoid haemorrhage. Ann Med. 1990;22:233–236.[Medline] [Order article via Infotrieve]

5. Suzuki H, Sato S, Suzuki Y, Takekoshi K, Ishihara N, Shimoda S. Increased endothelin concentration in CSF from patients with subarachnoid hemorrhage. Acta Neurol Scand. 1990;81:553–554.[Medline] [Order article via Infotrieve]

6. Hamann GF, Isenberg E, Strittmatter M, Stoll M, Keshevar T, Moiili R, Schimrigk K. Big endothelin in spontaneous intracerebral hemorrhage. Eur Neurol. 1994;34:99–102.[Medline] [Order article via Infotrieve]

7. Hamann GF, Schimrigk K. What is the relevance of the endothelins in subarachnoid haemorrhage? J Neurol Neurosurg Psychiatry. 1995;58:392.[Free Full Text]

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