Platelet activating factor receptor blockade enhances recovery after multifocal brain ischemia.
We treated four anesthetized dogs (Canis familiaris) with the platelet activating factor (PAF) receptor antagonist kadsurenone prior to 60 min of multifocal ischemia induced by air embolism, and measured neuronal recovery, blood flow and autologous 111In-labeled platelet accumulation for 4 h after ischemia. Four anesthetized animals with identical ischemia served as controls. Kadsurenone (3 mg/kg) administered 5 min prior to ischemia and continuously (1 mg/kg/hr) throughout ischemia and recovery significantly enhanced recovery of cortical somatosensory evoked response (CSER) amplitude (% of baseline) when compared to controls (27-36% vs 9-14%, p less than 0.05). We estimated platelet accumulation as 111In activity (cmp/g tissue) in the injured hemisphere minus that in the non-injured hemisphere. Kadsurenone treated animals did not exhibit significantly altered 111In-labeled platelet accumulation when compared to controls (6158 +/- 2386 vs 9979 +/- 3852, mean +/- SEM). Beneficial effects of PAF receptor blockade other than those on platelet accumulation may be involved.
Kochanek
P M
PM
Department of Anesthesiology, Children's Hospital National Medical Center, Washington, DC 20010.
Dutka
A J
AJ
Kumaroo
K K
KK
Hallenbeck
J M
JM
D000818:Animals; D001572:Benzofurans / Q000627:therapeutic use*; D002545:Brain Ischemia / Q000188:drug therapy* / Q000503:physiopathology; D002540:Cerebral Cortex / Q000503:physiopathology; D002560:Cerebrovascular Circulation; D004285:Dogs; D005073:Evoked Potentials, Somatosensory / Q000187:drug effects; D017705:Lignans; D008297:Male; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors*; D010980:Platelet Membrane Glycoproteins; D011956:Receptors, Cell Surface / Q000187:drug effects*; D043562:Receptors, G-Protein-Coupled
D001572:Benzofurans; D017705:Lignans; D010972:Platelet Activating Factor; D010980:Platelet Membrane Glycoproteins; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; C039351:platelet activating factor receptor; C044540:kadsurenone