Effect of systemic platelet-activating factor (PAF) on the rabbit spinal cord microcirculation.
Platelet-activating factor (PAF) is an endogenous phospholipid mediator with pro-inflammatory and vasoactive properties. Since PAF has been implicated in ischemic neuroinjury, we determined its effects on rabbit spinal cord microcirculation (SCM). Using laser-Doppler flow measurements, we monitored mean arterial pressure and SCM continuously on-line during and after i.v. infusion (1 min) of 0.5 nmol/kg of PAF (n = 20) and measured thromboxane B2 (TXB2) and 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) in arterial blood 1.5 min after the infusion. Responses were compared to those after indometacin pretreatment (4 mg/kg, n = 11). During the infusion, spinal cord blood flow (SCBF) decreased by 14 +/- 5% (P less than 0.05) paralleling the systemic hypotensive changes (17 +/- 5%, P less than 0.01) with no changes in vascular resistance (SCVR). However, immediately after termination of PAF infusion, SCVR decreased by 17 +/- 5% (P less than 0.01) while SCBF rapidly recovered. Plasma levels of both TXB2 and 6-keto-PGF1 alpha were significantly elevated. TXB2 release was correlated with the degree of hypotension during the PAF infusion (r greater than 0.72; P less than 0.05) while 6-keto-PGF1 alpha release correlated well with the decrease in SCVR during the infusion period (r greater than 0.64; P less than 0.05). Indomethacin blocked both the hemodynamic events and the eicosanoid release induced by PAF. Our data suggest that PAF modulates SCM through eicosanoid-mediated mechanism.
Lindsberg
P J
PJ
Department of Neurology, F. Edward Hebért School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD 20814-4799.
Jacobs
T P
TP
Paakkari
I A
IA
Hallenbeck
J M
JM
Feuerstein
G
G
D000818:Animals; D016718:Arachidonic Acid / Q000097:blood; D001773:Blood Cells / Q000187:drug effects; D001783:Blood Flow Velocity / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D002245:Carbon Dioxide / Q000097:blood; D006863:Hydrogen-Ion Concentration; D008297:Male; D008833:Microcirculation / Q000187:drug effects / Q000502:physiology; D010100:Oxygen / Q000097:blood; D010972:Platelet Activating Factor / Q000494:pharmacology* / Q000502:physiology; D011817:Rabbits; D013116:Spinal Cord / Q000098:blood supply / Q000187:drug effects*; D014655:Vascular Resistance / Q000187:drug effects
D010972:Platelet Activating Factor; D002245:Carbon Dioxide; D016718:Arachidonic Acid; D010100:Oxygen