Prevention of Vasospasm after Subarachnoid Hemorrhage in Dogs by Continuous Intravenous Infusion of PD156707

This randomized, blinded study tested the prophylactic effect of PD156707, a nonpeptide competitiveantagonist of endothelin A receptors, against vasospasm after subarachnoid hemorrhage in dogs.Twenty-two dogs were allocated on day 0 to undergo cerebral angiography followed by injection of arterialblood (0.5 ml/kg) into the cisterna magna. Dogs had central venous catheters implanted for continuousinfusion of drug vehicle (n=10) or PD156707 (n=12). Cisternal blood injection was repeatedon day 2. Drug levels were measured in plasma on days 2, 4, 6, and 7 and in cerebrospinal fluid (CSF) ondays 2 and 7. Angiography was repeated on day 7 to assess vasospasm. After angiography on day 7, acute effects of infusion of PD156707, 100 mg, or drug vehicle on established vasospasm were assessed.Analysis of physiological variables within (analysis of variance) groups across time and between (unpairedt-test) groups at each time showed that drug-treated animals had significantly increased heartrate on day 7 compared to day 0 (p