Aprotinin mediated antioxidant effect in Cardiosurgery with mechanical cardiorespiratory support (CMCS).

BACKGROUND: Aprotinin has been used in cardiosurgery as a hemostatic agent. Considering the implication of oxygen reactive species and proteases in the pathogenesis of Systemic Inflammatory Response Syndrome, we hypothesized that aprotinin may exert an antioxidant effect. This work was designed to evaluate the antioxidant capacity of aprotinin in vitro and in vivo in child patients undergoing cardiosurgery with mechanical cardiorespiratory support. METHODS: Colorimetric techniques and chemiluminiscent emission assays. A blind controlled clinical trial was performed with a control (G-1, n=14, without aprotinin) and treated with aprotinin (G-2, n=12) groups (both assessed by medical decision) of child patients undergoing cardiosurgery with mechanical cardiorespiratory support. Blood samples were taken at: T-0 (induction of anesthesia), T-1 (10 minutes after begining of perfusion), T-2 (5 minutes after anoxic heart arrest), T-3 (ending operation) and T-4 (24 hours after operation). RESULTS: We proved that aprotinin has no hydroxyl radical, superoxide anion nor H2O2 scavenger capacity as well as its capacity for inhibiting in vitro activated-leukocyte chemiluminiscence. Malonildialdehyde levels were higher in G-1 than G-2 with the greatest difference at T-2 (7.2+/-3.6 nmol/ml in G-1 vs 4+/-1.65 in G-2). Phospholipase A2 activity showed a tendency of higher values in G-1 than G-2 although there was no statistical significance. Uric acid concentration was greater in G-2 at T-1, T-2, T-3 and T-4 than G-1 and catalase activity was higher in G-2 at T-0, T-2 and T-3 than G-1 with noteworthy difference only at 5 minutes after anoxic heart arrest. Low cardiac output, arrhythmias and sudden death in the early postoperative phase were less frequent in the treated group. CONCLUSIONS: These results suggest that aprotinin exerts a primary antioxidant activity and its protective effects in cardiosurgery seem to be associated with reduction of systemic oxidative stress.

Aprotinin effects related to oxidative stress in cardiosurgery with mechanical cardiorespiratory support (CMCS).

There is evidence to support a relationship between oxidative stress and protease release in "ischemia-reperfusion damage." We have proposed that aprotinin may exert an antioxidant effect. A double blind clinical trial was performed with a control (G-1) and treated (G-2) groups, both submitted to CMCS. Blood samples were taken 5 times. Biochemical indicators were measured spectrophotometrically. Aprotinin was supplied by Bayer. Malonildialdehyde levels were greater in G-1 (7.2 +/- 3.6 nmoles/ml) than in G-2 (4 +/- 1.65) at the time of reperfusion. Phospholipase A2 exhibited a tendency of higher activity in G-1 than in G-2. Uric acid levels were higher in G-2 (431 +/- 274 mumoles/1) than in G-1 (224 +/- 188) at 5 minutes after aortic clamping, and catalase activity was greater in G-2 (294 +/- 55 KU/1) than in G-1 (118 +/- 47) at time of reperfusion. Low cardiac output was 10% in G-2 and 30% in G-1. Arrythmias appeared in 30% of G-2 and in 60% of G-1. These results suggest an antioxidant effect of aprotinin under ischemia-reperfusion conditions.