Platelet-activating factor receptor antagonism improves cerebral recovery after circulatory arrest.
BACKGROUND
The aim of this study was to determine the effects of antagonism of platelet-activating factor receptors on cerebral recovery after deep hypothermic circulatory arrest (DHCA).


METHODS
Fourteen 1-week-old piglets were randomly assigned to either placebo (n = 7), or 10 mg/kg intravenous ginkgolide B (BN52021), a naturally occurring platelet-activating factor receptor antagonist. All piglets had cardiopulmonary bypass, cooling to 18 degrees C, 60 minutes of circulatory arrest followed by 60 minutes of reperfusion and rewarming. Global and regional cerebral blood flow, cerebral oxygen metabolism and renal blood flow were determined at baseline before DHCA and after 60 minutes of reperfusion.


RESULTS
Blood flow was significantly reduced in all regions of the brain (p < 0.001) and the kidneys (p = 0.02) after DHCA in control animals. Cerebral oxygen metabolism was also significantly reduced after DHCA to 59.2% +/- 3.2% of the pre-DHCA value (p = 0.0003). In the ginkgolide B group, recovery of global cerebral blood flow to 60.4% +/- 2.8% of pre-DHCA level and of global cerebral oxygen metabolism to 77.1% +/- 5.8% of pre-DHCA value were significantly higher than the recovery in the control group (p < 0.02). Regional recovery of cerebral blood flow and oxygen metabolism in the gingkolide B group was greatest in the cerebellum and brainstem. Renal blood flow did not decrease significantly after DHCA in the gingkolide B group (p = 0.23).


CONCLUSIONS
These results suggest that production of platelet-activating factor is increased in the brain after DHCA. Platelet-activating factor receptor antagonism with ginkgolide B before the circulatory arrest period can significantly improve recovery of cerebral blood flow and oxygen metabolism and renal blood flow after DHCA.
Langley
S M
SM
Department of Surgery, Duke University Medical Center, Durham, North Carolina, USA. stephenlangley@dial.pipex.com
Chai
P J
PJ
Jaggers
J J
JJ
Ungerleider
R M
RM
D000818:Animals; D000831:Animals, Newborn; D001783:Blood Flow Velocity / Q000187:drug effects; D001921:Brain / Q000098:blood supply*; D004224:Diterpenes; D005343:Fibrinolytic Agents / Q000494:pharmacology*; D046934:Ginkgolides; D006324:Heart Arrest, Induced; D007668:Kidney / Q000098:blood supply; D007783:Lactones / Q000494:pharmacology*; D010101:Oxygen Consumption / Q000187:drug effects; D010980:Platelet Membrane Glycoproteins / Q000037:antagonists & inhibitors* / Q000502:physiology; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D012039:Regional Blood Flow / Q000187:drug effects; D013552:Swine
D004224:Diterpenes; D005343:Fibrinolytic Agents; D046934:Ginkgolides; D007783:Lactones; D010980:Platelet Membrane Glycoproteins; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; C039351:platelet activating factor receptor; C045856:ginkgolide B