1. ^*Department of Neurosurgery, Albert-Ludwigs-University, Freiburg i.B., Germany
2. ^†Department of Neurosurgery, Johann-Wolfgang-Goethe-University, Frankfurt/Main, Germany
3. ^‡Institute for Surgical Research, Ludwig-Maximilians-University, Munich, Germany
4. ^§Department of Neurosurgery, Technical University, RWTH, Aachen, Germany

Correspondence: Jens Lehmberg, Department of Neurosurgery, Breisacher Strasse 64, 79106 Freiburg, Germany; e-mail: lehmberg@nz.ukl.uni-freiburg.de

Received 16 July 2002; Revised 14 November 2002; Accepted 22 November 2002.

Abstract

The aim of the present study was to evaluate the influence of bradykinin on microcirculatory changes and outcome after global cerebral ischemia (15 minute) in Mongolian gerbils. The cerebral microcirculation was investigated by fluorescent intravital microscopy. Survival and functional outcome was evaluated up to 4 d after ischemia. Animals were treated with the selective B₁ and B₂ receptor antagonists B 9858 and CP 0597, respectively, and the nonselective B₁/B₂ receptor antagonist B 9430. Leukocyte activation was significantly reduced by all antagonists as indicated by a significant decrease in the number of rolling (33 20, 6 8, 9 10, and 13 10) and adherent leukocytes (9 7, 3 4, 1 1, and 2 3 100 m^-1 min^-1 in controls and in animals treated with B₁, B₂, and B₁/B₂ antagonist, respectively). Arteriolar diameters were significantly reduced during reperfusion (35 11 before and 27 8 m 40 minutes after ischemia) in animals treated with the B₂ antagonist. The postischemic hypoperfusion, however, was not affected. Mortality was significantly higher in animals treated with the B₁ and the B₁/B₂ antagonist. The authors concluded that bradykinin is involved in postischemic disturbances of cerebral microcirculation. The therapeutic effect of specific bradykinin receptor antagonists on functional outcome, however, remains unclear.