Abstract

Retrograde cerebral perfusion (RCP) techniques have been adopted in aortic arch surgery for clinical use. The clear benefits of RCP are that it reduces embolic injury and prolongs the permissible period of hypothermic circulatory arrest (HCA). At the same time, however, there is a great deal of evidence according to which RCP may be associated with an increased risk of fluid sequestration and cerebral edema. In the current study intermittent RCP was compared with continuous RCP and HCA alone to clarify if periodical RCP decreases fluid sequestration (I).

HCA is an effective method of cerebral protection, but is associated with long cardiopulmonary bypass times, and coagulation disturbances. We tested the hypothesis that deep hypothermic RCP could improve cerebral outcome during moderate HCA (II and III).

Glutamate excitotoxicity plays an important role in the development of ischemic brain injury. The purpose of the present study was to determine the efficacy of lamotrigine, a Na⁺ channel blocker, to mitigate cerebral injury after HCA (IV). A chronic porcine model was used in the present series of studies. Hemodynamic, electrophysiologic, and metabolic monitoring were performed until four hours after the instigation of rewarming. S-100β was measured up to 20 hours. Daily behavioral assessment performed until death or elective sacrifice on the seventh postoperative day.

After continuous RCP the median fluid sequestration volume was 145 (0–250) ml compared with −50 (−100–0) ml after intermittent RCP (p = 0.04). In comparison of 15°C RCP to HCA alone during moderate 25°C hypothermia, 5/6 animals in the RCP group survived seven days compared with 2/6 in the HCA group (p = 0.04).

The total histopathologic scores in the RCP(15°C) group were lower than those for the RCP(25°C) group during moderate 25°C hypothermia (p = 0.04). EEG bursts were recovered better in the RCP(15°C) group at 3 hours after the start of rewarming compared to HCA group (p = 0.05).

The rate of EEG burst recovery was higher in lamotrigine treated animals compared to placebo treated animals after 4 hours during the rewarming (p = 0.02). Among the animals that survived for 7 days, the median behavioral score was higher in the lamotrigine group (8) compared with controls (7) (p = 0.02). The results indicate that intermittent RCP decreases the rate of fluid sequestration after continuous RCP. The cold RCP at moderate systemic hypothermia seems to provide a better neurological outcome than that with moderate temperature RCP, a finding suggesting that enhanced cranial hypothermia is the major beneficial factor of RCP. The Na+ channel blocker lamotrigine improves neurological outcome after a prolonged period of HCA. In conclusion, two refinements in the RCP concept are to administer it at low temperatures and if longer periods of perfusion are necessary, RCP should be applied intermittently.