Activity of alpha 1-antitrypsin and cigarette smoking in subarachnoid haemorrhage from ruptured aneurysm

An altered equilibrium of protease/protease-inhibitor factors may be involved in the pathogenesis of aneurysm rupture: alpha 1-antitrypsin (alpha 1-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 alpha 1-AT on proteases. In the present study we test the hypothesis whether the activity of alpha 1-AT is altered in patients with subarachnoid haemorrhage (SAH) and if is there any relationship between alpha 1-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 alpha 1-AT level was determined by immunoturbidimetric method. In order to obtain qualitative data about the anti-protease activity of alpha 1-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 alpha 1-AT in controls does not significantly differ from other groups. The mean serum level of alpha 1-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 alpha 1-AT levels in each subgroup of patients. A multivariate analysis considering alpha 1-AT CIC, showed that alpha 1-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 alpha 1-AT CIC and smoking habit in each group the covariance analysis showed that while in controls and unruptured aneurysms there is no difference in alpha 1-AT CIC between smokers and non smokers, in cases of SAH, cigarette smoking significantly influences the alpha 1-AT CIC. The present results suggest that the basic mechanism behind the increased risk of SAH in smokers involves a qualitative deficiency of alpha 1-AT.