Cariporide (HOE642) limits S-100B release during cardiac surgery

Abstract

Cardiac surgery with cardiopulmonary bypass (CPB) results in transient cerebral swelling in most patients. Cognitive decline occurs in 24-57% of patients and 2-5% experience stroke. Serum levels of S-100B, a potential marker of increased blood-brain barrier permeability, increase during and early after surgery. The authors studied the effects of the novel Na /H exchange inhibitor cariporide (HOE642) on postoperative serum levels of S-100B and neuron-specific enolase (NSE) in 53 patients at high risk undergoing coronary artery bypass grafting. Patients were randomly assigned to one of four groups: I, placebo; II, 20 mg cariporide; III, 80 mg cariporide; IV, 120 mg cariporide). In addition, the leukocyte activation marker myeloperoxidase (MPO) and malondialdehyde (MDA), a marker for lipid peroxidation, were evaluated by enzyme-linked immunoassay. Postoperatively, five patients experienced transient ischemic attack or stroke. S-100B levels increased from 0.43 microg/l +/- 0.33 before operation to 2.27 microg/l +/- 0.69 1 hour after surgery in the placebo group. Preoperative S-100B levels in the HOE642 groups did not differ from the placebo group whereas, 1 hour after surgery, levels were significantly lower in groups II, III, and IV (1.63 microg/l +/- 0.2, 1.27 microg/l +/- 0.27, and 0.90 microg/l +/- 0.21, respectively). NSE, MPO, and MDA serum levels did not differ among groups. These findings may stimulate larger clinical studies to examine the effects of HOE642 on cerebral swelling and neurologic/cognitive outcome of cardiac surgery with CPB.