C-type natriuretic peptide concentrations in the plasma and cerebrospinal fluid of patients with subarachnoid hemorrhage

Abstract

Cerebral vasospasm is a poor resulting outcome of a ruptured cerebral aneurysm; to clarify the mechanism of vasospasm it is important to improve this outcome. C-type natriuretic peptide (CNP) is present in the brain as a cerebral vasodilator; it is also an endothelium-derived relaxing factor produced via cGMP. We speculated that CNP might be an inhibitor of cerebral vasospasm after subarachnoid hemorrhage (SAH). To clarify the role of CNP in cerebral vasospasm after SAH, we conducted 1 week monitoring of CNP concentrations in the plasma and cerebrospinal fluid (CSF) of 26 patients who had undergone clipping within 24 hours of the occurrence of SAH, and divided them into group A (positive for angiographic spasm) and group B (negative for angiographic spasm). We also examined CNP concentrations in the CSF of patients who were receiving spinal anesthesia for small orthopedic operations, as reference patients. The CNP concentration in the CSF on day 1 was higher than in the reference patients and decreased in both test groups, but we did not observe any significant difference between the groups. CNP concentrations in the plasma did not change in either group. CNP concentrations in the CSF were high in the acute phase after SAH, whereas plasma CNP concentrations remained constant. However, our findings did not support our hypothesis because we did not find any relationship between vasospasm and changes in CNP concentrations in the CSF.

Background:

Cerebral vasospasm is a poor resulting outcome of a ruptured cerebral aneurysm; to clarify the mechanism of vasospasm it is important to improve this outcome. C-type natriuretic peptide (CNP) is present in the brain as a cerebral vasodilator; it is also an endothelium-derived relaxing factor produced via cGMP. We speculated that CNP might be an inhibitor of cerebral vasospasm after subarachnoid hemorrhage (SAH).

Methods:

To clarify the role of CNP in cerebral vasospasm after SAH, we conducted 1 week monitoring of CNP concentrations in the plasma and cerebrospinal fluid (CSF) of 26 patients who had undergone clipping within 24 hours of the occurrence of SAH, and divided them into group A (positive for angiographic spasm) and group B (negative for angiographic spasm). We also examined CNP concentrations in the CSF of patients who were receiving spinal anesthesia for small orthopedic operations, as reference patients.

Results:

The CNP concentration in the CSF on day 1 was higher than in the reference patients and decreased in both test groups, but we did not observe any significant difference between the groups. CNP concentrations in the plasma did not change in either group.

Conclusions:

CNP concentrations in the CSF were high in the acute phase after SAH, whereas plasma CNP concentrations remained constant. However, our findings did not support our hypothesis because we did not find any relationship between vasospasm and changes in CNP concentrations in the CSF.

Introduction

].

]. On the basis of these previous findings, we assumed that CNP might have vasodilator effects to inhibit vasospasm after SAH, and conducted the present study to determine the relationship between the changes in CNP with cerebral vasospasm after SAH.

Patients and methods

This study was approved by an ethical committee of our university, and we obtained informed consent for enrolled patients, including those patients used as a reference.

]. They were divided into group A (positive for angiographic spasm) and group B (negative for angiographic spasm).

We performed angiography several times as required, and classified the patients according to the angiographic findings from days 5-7.

summarizes the characteristics of group B. Their age (mean ± SD) was 59.3 ± 14.6 years.

CNP concentrations in the plasma and CSF were measured on days 1, 3 and 7 of hospitalization. Blood samples were obtained with a radial arterial catheter and were centrifuged at 4°C. Plasma was separated, frozen immediately and stored at -20°C until analysis. CSF samples were obtained with a cisternal drain or ventricular drain inserted during surgery. After the removal of blood from the sample, the CSF was stored at -20°C until analysis.

]. To obtain reference data, 1-2 ml of CSF was sampled from 20 patients who were receiving spinal block anesthesia for small orthopedic operations. CSF sampling from the reference patients was conducted only at surgery.

values of less than 0.05 were considered statistically significant.

Results

. Plasma concentrations are in the normal ranges and did not change significantly within the first week after the onset of SAH. We also did not observe any significant difference between the groups.

The CNP level in the CSF of twelve patients of group A and eight patients of group B was higher on day 1 than the reference data (13.5 ± 4.7 pg/ml), but mean levels in both groups were not significantly higher than the reference data. CNP concentrations in the CSF decreased gradually in both groups, but these changes were not significant. We also did not observe any significant difference in the data between the groups.

Discussion

This preliminary study indicated that CNP in CSF could act as a vasodilator when vasospasms occur in the brain. However, many test patients showed a higher value of CNP in the CSF on day 1 than the reference data, and CNP in the CSF decreased gradually for 1 week, whereas CNP in the plasma did not change. However, this phenomenon was independent of cerebral vasospasms.

].

], and its levels were 10-fold those of ANP and BNP.

] who showed that plasma ANP and BNP levels increased after SAH, whereas plasma CNP and endothelium CNP were independent of ANP and BNP and did not change very much. We also compared the data with regard to the severity of the spasm and the outcome but found no correlation.

From our findings, we can say that CNP concentration in the CSF was high in the acute phase and decreased gradually after SAH, whereas CNP in the plasma did not change. However, we could not clarify the mechanism of this phenomenon.

Figures and Tables

Characteristics of patients in group A

Outcome was evaluated with the Glasgow Outcome Scale. Mean age (± SD) was 53.8 ± 7.6 years. AN, aneurysm; AcomA, anterior communicating artery; D, death; ICPC, internal carotid-posterior communicating artery; GR, good recovery; MCA, middle cerebral artery; MD, moderate disability; SD, severe disability; VS, vegetative state; WFNS, World Federation of Neurosurgical Societies SAH grade.

Characteristics of patients in group B

Outcome was evaluated with the Glasgow Outcome Scale. Mean age (± SD) was 59.3 ± 14.6 years. AN, aneurysm; AcomA, anterior communicating artery; BA, basilar artery; D, death; ICPC, internal carotid-posterior communicating artery; GR, good recovery; MCA, middle cerebral artery; VS, vegetative state; WFNS, World Federation of Neurosurgical Societies SAH grade.

C-type natriuretic peptide (CNP) levels in the plasma

The normal level of CNP was less than 4 pg/ml. Figures are means ± SD. Day 1 is the day of hospitalization.

C-type natriuretic peptide levels in the cerebrospinal fluid

The reference level was 13.5 ± 4.7 pg/ml. Figures are means ± SD. Day 1 is the day of hospitalization.

Keywords

• cerebral vasospasm
• C-type natriuretic peptide
• subarachnoid hemorrhage