Effect of allopurinol and dimethylsulfoxide on long-term survival in rats after cardiorespiratory arrest and resuscitation

The effects of allopurinol and dimethylsulfoxide (DMSO) upon reperfusion injury were tested in separate studies that utilized a rat model of cardiorespiratory arrest and resuscitation. The rats were subjected to 7 minutes of arrest followed by resuscitation, and then were alternately assigned to either a drug-treated group or a vehicle-treated group (n = 22 for all groups). Drug treatment was given after the return of spontaneous circulation, and survival was monitored for a ten-day period. Study 1 utilized DMSO (50% solution, 1 ml/kg) as the test drug and saline solution as the vehicle. The percentages of surviving rats in the DMSO-treated and vehicle-treated groups were never statistically significantly different. There were 59% ( 13 23) of the DMSO-treated rats and 63% ( 14 22) of the vehicle-treated rats alive at one hour after resuscitation. Survival rates decreased to 18% ( 4 22) of DMSO-treated rats and 22% ( 5 22) of vehicle-treated rats on days 3 through 10. Allopurinol (25 mg/kg) was the test drug in study 2, and 0.18-M sodium hydroxide was the vehicle. The survival rate of resuscitated rats was statistically significantly greater at two days in the drug-treated group (68%, 15 22) than in the vehicle-treated group (36%, 8 22) (χ² = 4.46, df = 1, P < 0.05). The difference increased to a maximum of 68% ( 15 22) of the allopurinol-treated group versus 27% ( 6 22) of the vehicle-treated group at days 7 and 8 (χ² = 7.38, df = 1, P < 0.01), and remained statistically significant at day 10, with 64% ( 14 22) of allopurinol-treated versus 27% ( 6 22) of vehicle-treated rats alive (χ² = 5.87, df = 1, P < 0.05). Neurological deficit scores were not different between the drug-treated and vehicle-treated groups at day 10 in either study. It is concluded that reperfusion injury is preventable with allopurinol, but not DMSO, when given after successful resuscitation from cardiopulmonary arrest in the rat model. It is also speculated that allopurinol is the more effective drug because it blocks an early step in the initiation of free-radical-mediated injury.