Cariporide (HOE642) limits S-100B release during cardiac surgery.
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.
Scholz
Martin
M
Department of Thoracic and Cardiovascular Surgery, JW Goethe Universität, Frankfurt, Germany. m.scholz@em.uni-frankfurt.de
Wimmer-Greinecker
Gerhard
G
Kleine
Peter
P
Dzemali
Omer
O
Martens
Sven
S
Moritz
Anton
A
Matheis
Georg
G
D000368:Aged; D001026:Coronary Artery Bypass / Q000379:methods; D005260:Female; D006146:Guanidines / Q000494:pharmacology*; D006801:Humans; D008297:Male; D009414:Nerve Growth Factors; D011184:Postoperative Period; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins / Q000037:antagonists & inhibitors* / Q000097:blood / Q000378:metabolism*; D018709:Statistics, Nonparametric; D013450:Sulfones / Q000494:pharmacology*
D006146:Guanidines; D009414:Nerve Growth Factors; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins; D013450:Sulfones; C093373:cariporide