Activity of α1-antitrypsin and cigarette smoking in subarachnoid haemorrhage from ruptured aneurysm

• Published in: Journal of the neurological sciences 1996-09, Vol.141 (1), p.33-38
• Main Authors: Gaetani, Paolo, Tartara, Fulvio, Tancioni, Flavio, Klersy, Catherine, Forlino, Antonella, Baena, Riccardo Rodriguez y
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; Cigarette smoking; Intracranial aneurysm; Medical sciences; Neurology; Subarachnoid haemorrhage; Vascular diseases and vascular malformations of the nervous system; α1-Antitrypsin
• ISSN: 0022-510X; 1878-5883
• DOI: 10.1016/0022-510X(96)00132-3

An altered equilibrium of protease/protease-inhibitor factors may be involved in the pathogenesis of aneurysm rupture: α1-antitrypsin (α1-AT) represents the most relevant inhibitor of elastase, a proteolytic enzyme enhancing catabolic processes of collagen metabolism. Cigarette smoking has been shown to significantly reduce the inhibitory effect of α1-AT on proteases. In the present study we test the hypothesis whether the activity of α1-AT is altered in patients with subarachnoid haemorrhage (SAH) and if is there any relationship between α1-AT activity and the high risk of aneurysm rupture in smokers. The patients were subdivided in the following groups: (a) patients with unruptured aneurysm ( n = 10); (b) patients presenting with SAH admitted within 48 h after the episode ( n = 20); (c) patients presenting with SAH admitted >48 h after the episode ( n = 14); (d) controls ( n = 10): patients with neither cerebrovascular nor acute disease. Blood samples were obtained immediately at admission. Measurement of α1-AT level was determined by immunoturbidimetric method. In order to obtain qualitative data about the anti-protease activity of α1-AT (expressed as collagenase inhibitory percentage capacity (CIC) at different doses) we consider the 20 cases admitted for SAH within 48 h. The mean serum level of patients with unruptured aneurysms is significantly lower than that of patients with SAH ( p < 0.01), while the mean serum level of α1-AT in controls does not significantly differ from other groups. The mean serum level of α1-AT in patients admitted >48 h after SAH is significantly higher than that of patients admitted within 48 h after the haemorrhage ( p < 0.02). Considering the smoking habit of patients, there is no significant difference in α1-AT levels in each subgroup of patients. A multivariate analysis considering α1-AT CIC, showed that α1-AT CIC in patients with ruptured aneurysms is significantly reduced if compared to controls and unruptured aneurysms ( F = 50.759; p < 0.001). Moreover, considering α1-AT CIC and smoking habit in each group the covariance analysis showed that while in controls and unruptured aneurysms there is no difference in α1-AT CIC between smokers and non smokers, in cases of SAH, cigarette smoking significantly influences the α1-AT CIC. The present results suggest that the basic mechanism behind the increased risk of SAH in smokers involves a qualitative deficiency of α1-AT.