Treatment with an endothelin type A receptor-antagonist after cardiac arrest and resuscitation improves cerebral hemodynamic and functional recovery in rats

Objective: Successful resuscitation of the brain after cardiac arrest requi res unimpaired microcirculatory reperfusion. Postischemic cerebral hypoperf usion presumably is mediated through activation of endothelin type A recept ors (ETA). The effect of the selective ETA antagonist BQ123 on cerebral blo od flow and function was studied in a rat model of cardiac arrest. Design: Prospective, randomized trial. Setting: Experimental animal laboratory. Subjects: Twelve male Sprague-Dawley rats (290-350 g). Interventions: Cardiac arrest for 12 mins was induced by electrical fibrill ation of the heart, followed by standardized cardiopulmonary resuscitation. BQ123 (0.8 mg/kg; n = 6) or its vehicle (saline; n = 6) was injected intra venously at 15 mins after the return of spontaneous circulation. Measurements: Cortical blood flow was measured by laser-Doppler flowmetry, electrophysiological function by recording the amplitude of somatosensory e voked potentials, vascular reactivity by ventilation with 6% CO2, and the f unctional coupling of blood flow by recording the laser-Doppler flow (LDF) changes during somatosensory stimulation. Hemodynamic and functional cerebr al recovery was monitored for 3 hrs after the return of spontaneous circula tion. Main Results: Forty-five minutes after the return of spontaneous circulatio n, postischemic hypoperfusion developed in both groups, as reflected by a d ecrease of the LDF signal to about 60% of the preischemic level. In untreat ed animals, hypoperfusion persisted throughout the observation time, but in animals receiving BQ123, LDF gradually returned to normal. CO2 reactivity in untreated animals was severely reduced for 2-3 hrs after the onset of re circulation, whereas after BQ123 treatment it returned to normal and after 2 hrs even above normal. The ETA antagonist also induced a more rapid recov ery of the somatosensory evoked potentials amplitude and of the functional blood flow response to somatosensory stimulation, but these parameters did not recover completely within the observation period. Conclusions: Application of the ETA antagonist BQ123 during the early reper fusion period after cardiac arrest shortens postischemic cerebral hypoperfu sion and accelerates the restoration of the cerebrovascular CO2 reactivity and the recovery of electrophysiologic function,