Prostaglandin I2, indomethacin, and heparin promote postischemic neuronal recovery in dogs.
Forty-five conditioned male mongrel dogs were exposed to multifocal ischemia sufficient to maintain suppression for 60 minutes of the P1-N1 amplitude of the cortical sensory evoked response (CSER), a quantifiable index of neuronal function. Ischemia was induced and regulated by successive embolization of 20 to 50 microliters increments of air via the right internal carotid artery. Subsequently, the P1-N1 amplitude recovery of the CSER was followed for an additional 15, 60, or 120 minutes while the dogs were treated or left untreated. The combination of prostaglandin I2 (PGI2), indomethacin, and heparin promoted a statistically significant augmentation of return of CSER amplitude relative to no treatment, PGI2 alone, indomethacin alone, PGI2 and heparin, indomethacin and heparin, or PGI2 and indomethacin. After 60 minutes of recovery, animals receiving combined PGI2, indomethacin, and heparin achieved a 57% recovery of P1-N1 amplitude relative to baseline, while the corresponding recoveries in all other groups clustered around 20%. By 120 minutes of postischemic follow-up, the CSER recovery induced by PGI2, indomethacin, and heparin was 80% compared to 17% in untreated animals. By 15 minutes into the recovery period, the combination of the three agents had eliminated very low flows in the "neuron-disabling" range (defined as 0 to 15 ml/100 gm/min for gray matter and 0 to 6 ml/100 gm/min for white matter) in contrast to the relative inefficacy of no treatment or treatment with other than the triple combination of drugs. The study lends some support to a planned clinical trial of PGI2, indomethacin, and heparin in acute occlusive stroke in humans.
D000818:Animals; D002545:Brain Ischemia / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D002540:Cerebral Cortex / Q000648:ultrastructure; D002560:Cerebrovascular Circulation; D004285:Dogs; D004359:Drug Therapy, Combination; D011464:Epoprostenol / Q000627:therapeutic use*; D005073:Evoked Potentials, Somatosensory; D006493:Heparin / Q000627:therapeutic use*; D007213:Indomethacin / Q000627:therapeutic use*; D008297:Male; D011453:Prostaglandins / Q000627:therapeutic use*
D011453:Prostaglandins; D006493:Heparin; D011464:Epoprostenol; D007213:Indomethacin