Calcitonin gene-related peptide (human alpha-CGRP) counteracts vasoconstriction in human subarachnoid haemorrhage

Calcitonin gene-related peptide (CGRP) is a neuropeptide co-stored with tachykinins (substance P, neurokinin A) in cerebrovascular sensory fibers in the trigeminal ganglion. Preceding studies on subarachnoid hemorrhage (SAH) revealed that an enhanced release of CGRP resulted in the selective loss of perivascular CGRP. Therefore, the present study was designed to evaluate the effects of intravenous administration of human alpha-CGRP on cerebral vasoconstriction in the postoperative course after SAH in 5 patients (8 infusions). Cerebral vasoconstriction was evaluated with transcranial Doppler sonography. The increase in the relationship between middle cerebral artery (MCA) velocity and internal carotid artery (ICA) velocity (the hemodynamic index) was used as an indicator of vasoconstriction and compared to the contralateral side. A significant reduction was found in the hemodynamic index during the CGRP infusion (4.3 +/- 0.5, P < 0.05) as to compared to before infusion (6.2 +/- 0.5). There was no measurable change in the hemodynamic index on the contralateral side. No significant change was observed in pulsatility index, blood pressure or consciousness during the peptide infusion. A significant increase in heart rate was observed during the infusion as compared to before and after infusion (90 +/- 4 vs. 76 +/- 5). Cardiac ultrasound data indicated a mean cardiac output increase of 1.9 liter/min, and a mean decrease in total peripheral resistance of 538 dynes s/cm5. The results obtained show that infusion of human alpha-CGRP may induce normalisation of cerebrovascular tone in SAH.