Treatment of severe brain ischemia with di- and tri-Calciphor (dimer and trimer of 16,16'-dimethyl prostaglandin B1).
Following 20 min occlusion of both carotid arteries, female gerbils were subjected to treatment with di- or tri-Calciphor (dimer or trimer of 16,16'-dimethyl prostaglandin B1). Dimer was injected i.p. at 5 and 10 mg/kg at 5 min and again at 24 h, 30 min and 24 h, 60 min and 24 h or 180 min and 24 h postischemia (N = 25/group). Trimer was given i.p. at 5, 10 or 15 mg/kg at 5 min and 24 h postischemia (N = 25/group.) The controls (N = 25) were injected with the vehicle. Neurological status and postischemic survival of the animals were monitored for 14 days postischemia. Survival of the treated gerbils was significantly improved following the treatment with either di- or tri-Calciphor administered at 10 mg/kg at 5 min and 24 h postischemia (36 vs. 68% di- and 64% tri-Calciphor, P less than 0.05), and with di-Calciphor at 5 mg/kg at 180 min and 24 h postischemia (64%). All other treatment regimens with either drug resulted in a numerical, statistically insignificant improvement. In addition, treatment with either drug reduced the intensity of postischemic neurological impairment. Treatment with di-Calciphor injected at 10 mg/kg at 5 min and 24 h post 20 min ischemia substantially reduced the period of postischemic locomotor hyperactivity. The drug had no impact on either body temperature or blood pressure. There is evidence that the effects of Calciphor may be mediated via calcium regulatory mechanisms. The results of the present study are discussed in the light of such possibility.
Von Lubitz
D K
DK
Department of Biochemistry, Hahnemann University School of Medicine, Philadelphia, PA 19102.
McKenzie
R J
RJ
Kalenak
A
A
Lin
R C
RC
Devlin
T M
TM
D000704:Analysis of Variance; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D001831:Body Temperature / Q000187:drug effects*; D002545:Brain Ischemia / Q000188:drug therapy* / Q000503:physiopathology; D005260:Female; D005849:Gerbillinae; D009043:Motor Activity / Q000187:drug effects*; D011456:Prostaglandins B / Q000494:pharmacology / Q000627:therapeutic use*
C052137:16,16-dimethyl-15-dehydroprostaglandin B1 trimer; D011456:Prostaglandins B; C076722:di-Calciphor