INACTIVATION OF ALPHA-1-ANTIPROTEINASE (ALPHA-1-AT) AND CHANGES IN ANTIOXIDANTS PLASMA-LEVELS IN SUBARACHNOID HEMORRHAGE

Recent studies have suggested that a quantitative or a qualitative imb alance between the activity of proteases and its inhibitors hypothetic ally might be involved in intracranial aneurysm rupture. Ln the presen t study we test the hypothesis that the systemic reduction of alpha 1- antitrypsin activity might be related to the elevated oxidative potent ial exerted by cigarette smoking and/or to a systemic low antioxidant capacity. We studied, in a series of 57 patients bearing intracranial aneurysms, the relationship between alpha 1-antitrypsin activity, ciga rette smoking and the following variables measured in plasma: vitamin A, vitamin E, thiol groups, urate and lipid peroxide levels. Serum lev els of alpha 1-antitrypsin are higher in patients with subarachnoid he morrhage than in cases of unruptured aneurysms, while the levels of vi tamin A and vitamin E are significantly lower in patients that suffere d subarachnoid hemorrhage than in controls. Both vitamin A and E level s are related to the occurrence of rupture of the aneurysm, as elicite d by logistic regression analysis (P=0.017 and P=0.014, respectively), with a protective effect of higher levels of the variables, as shown by their odds ratio (0.028 and 0.84, respectively), No significant cha nges in the strength of the association could be appreciated when cont rolling for smoking habit. None of the other tested variables could be related to the occurrence of the aneurysm rupture. Both alpha 1-antit rypsin serum level and the level of vitamin A appeared to be independe ntly related to alpha 1-antitrypsin collagenase inhibitory capacity pe rcentage (P=0.03 and P=0.025), with no independent influence of the ty pe of aneurysm and the smoking habit. The results of the present study show that the qualitative pattern of alpha 1-antitrypsin is significa ntly related to the serum level of liposoluble vitamin A, while the ty pe of aneurysm and the smoking habit have no independent influence. Th is suggests that in a situation in which systemic levels of vitamin A are reduced, the risk of a reduced activity of alpha 1-antitrypsin as controller of proteases is elevated, with the consequent increased ris k of aneurysm bleeding. (C) 1997 Elsevier Science B.V.