Endothelin type A-antagonist improves long-term neurological recovery after cardiac arrest in rats

Objective: Antagonists of endothelin (ETA) receptors improve postischemic h ypoperfusion. In this study we investigated whether the selective ETA-antag onist BQ123 also improves postischemic functional recovery. Study Design: Cardiac arrest of 12 mins duration was induced in rats by ele ctrical fibrillation of the heart, followed by advanced cardiopulmonary res uscitation. BQ123 (0.8 mg/kg; n = 9) or its vehicle (saline; n = 9) was inj ected intravenously at 15 mins after the return of spontaneous circulation. The neurologic deficit was scored daily for 7 days after resuscitation by rating consciousness, various sensory and motor functions, and coordination tests. On day 7, we measured functional coupling of cerebral blood flow un der halothane anesthesia by recording laser-Doppler flow during electrical forepaw stimulation, and we measured vascular reactivity to CO2 by measurin g the laser-Doppler flow change during ventilation with 6% CO2. The brains were perfusion-fixated with 4% paraformaldehyde, and the histopathologic da mage was evaluated in the CA1 sector of hippocampus, in the motor cortex, a nd in the cerebellum. Results: Treatment with BQ123 had no effect on histopathologic damage, but it significantly improved neurologic recovery. In all nine treated rats, ne urologic performance returned to near normal within 2 days whereas four of nine untreated animals developed spastic paralysis of the hind limbs and se vere coordination deficits. BQ123 also normalized CO2 reactivity and improv ed the functional cerebral blood flow response to somatosensory stimulation . Conclusions: The ETA-antagonist BQ123 significantly improves neurologic out come after 12 mins of cardiac arrest. The apparent restoration of vascular reactivity demonstrates a correlation between hemodynamic factors and funct ional recovery.