Effects on improvement of blood flow in the chronically compressed cauda equina: comparison between a selective prostaglandin E receptor (EP4) agonist and a prostaglandin E1 derivate.
METHODS
Vasodilatation was studied in a model of experimental chronic cauda equina compression using measurements of vessel diameter on video recordings.


OBJECTIVE
The vasodilative effect was compared between a prostaglandin E2 receptor (EP) subtype agonists (EP4 agonist) and a prostaglandin E1 (PGE1) derivate.


BACKGROUND
Reduction of blood flow is one important pathogenic factor of neurogenic intermittent claudication (NIC) for lumbar spinal canal stenosis. It is known that PGE1 improves the mean walking distance in patients with cauda equina compression type of NIC. There are four subtypes of EP: EP1, EP2, EP3, and EP4. EP4 is located in vessels of pigs and rabbits. A highly selective EP4 agonist, which has effects on dilatation of pig and rabbit vessels, has recently been developed. One may therefore assume that this agonist may improve blood flow in the chronically compressed cauda equina.


METHODS
A total of 25 dogs were used. A plastic balloon inflated to 10 mm Hg was placed under the lamina of the seventh lumbar vertebra for 1 week. OP-1206 cyclodextrin clathrate (OP-1206 CD: prostaglandin E1 derivate) and ONO-4819 CD (a highly selective EP4 agonist) were intravenously administrated. The following 5 experimental groups were assigned: animals in group OP (3) (n = 5) and Group OP (10) (n = 5) received 3 eta g/kg per minute and 10 eta g/kg per minute of OP-1206 CD, respectively; those in Group EP (3) (n = 5) and Group EP (10) (n = 5) received 3 eta g/kg per minute and 10 eta g/kg per minute of ONO-4819 CD, respectively; and those in the control group (n = 5) received saline. After 7 days, the cauda equina was exposed and blood vessels of the second or third sacral nerve root were identified using a specially designed operation microscope equipped with a video camera. The diameters of the observed blood vessels were measured on video-recordings every 10 minutes until 60 minutes after administrating OP-1206 CD or ONO-4819CD.


RESULTS
In the Groups OP (3), OP (10), and EP (10), the blood vessels were dilated and blood flow increased after injection of the agents. In the Group EP (10), the vessel diameter and blood flow increased significantly compared with that in the other four groups. In contrast, the blood vessels contracted and the blood flow was reduced in the Group EP (3).


CONCLUSIONS
Our results suggested that the EP4 agonist at high concentrations might be a potential therapeutic agent since it is expected to increase blood flow in nerve roots in patients with spinal canal stenosis.
Sekiguchi
Miho
M
Department of Orthopaedic Surgery, Fukushima Medical University School of Medicine, Fukushima City, Fukushima, Japan. miho-s@fmu.ac.jp
Konno
Shin-ichi
S
Kikuchi
Shin-ichi
S
D000527:Alprostadil / Q000031:analogs & derivatives / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D002420:Cauda Equina / Q000098:blood supply* / Q000187:drug effects* / Q000502:physiology; D004285:Dogs; D018078:Receptors, Prostaglandin E / Q000819:agonists* / Q000502:physiology; D058309:Receptors, Prostaglandin E, EP4 Subtype; D012039:Regional Blood Flow / Q000187:drug effects / Q000502:physiology; D013117:Spinal Cord Compression / Q000188:drug therapy* / Q000503:physiopathology; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology
D018078:Receptors, Prostaglandin E; D058309:Receptors, Prostaglandin E, EP4 Subtype; D000527:Alprostadil