Differences in intraischemic temperature influence neurological outcome after deep hypothermic circulatory arrest in newborn dogs.

BACKGROUND AND PURPOSE

Hypothermia to core temperatures ranging from 16 degrees C to 24 degrees C has become an established procedure to extend the "safe" interval of cardiac arrest during open heart surgery in human infants. The present experiment was designed to ascertain whether differences in core (rectal) temperature during hypothermic circulatory arrest influence the presence and extent of ischemic brain damage in newborn dogs.

METHODS

Newborn dogs (postnatal age, 3 to 5 days) were anesthetized with halothane (4% induction; 0.5% maintenance), intubated, paralyzed, and artificially ventilated with 70% nitrous oxide/30% oxygen. Thereafter, the dogs were surface cooled with ice packs to either 16 degrees C (n = 6), 20 degrees C (n = 8), or 24 degrees C (n = 6). The dogs then were subjected to circulatory arrest for 1.75 hours by the intravenous injection of KCl, following which they were resuscitated with intravenous NaHCO3 and epinephrine, artificial ventilation, and closed chest cardiac massage. Those dogs that survived for 8 hours of recovery (n = 16) underwent neurobehavioral examination followed by perfusion-fixation of their brains for pathological analysis.

RESULTS

All newborn dogs were successfully resuscitated after 1.75 hours of cardiac arrest, rewarmed to 37 degrees C, and ultimately weaned from anesthesia and ventilatory support. Four dogs sustained secondary systemic complications with death at 4 to 7 hours. All surviving dogs remained stable, with systemic blood pressure, heart rate, arterial oxygen, and acid-base balance within the normal, normothermic range. Of the 16 surviving dogs, all except 1 showed histological evidence of brain damage at 8 hours of recovery. Morphometric analysis of the number of necrotic neurons in the vulnerable gray matter structures showed the greatest damage to cerebral cortex at 24 degrees C and the least damage to this structure at 16 degrees C by either regression analysis (r = .62; P = .01) or a repeated-measures model (P = .008). The extent of damage to the caudate nucleus was similar in the three temperature groups, while damage to the amygdaloid nucleus was greater at 24 degrees C compared with 20 degrees C but with no difference in the severity of damage between 20 degrees C and 16 degrees C. A close correlation existed between neurobehavioral deficits in the surviving dogs and the severity of damage to the cerebral cortex (r = .72; P = .001).

CONCLUSIONS

The findings indicate that differences in intraischemic core temperature during deep hypothermic circulatory arrest influence the severity of damage to the cerebral cortex of newborn dogs. Specifically, the lower the temperature below 24 degrees C, the more protected the structure from ischemic injury. Furthermore, the greater the cortical damage, the more severe the neurobehavioral deficits. Such was not the case for the amygdaloid nucleus and especially for the caudate nucleus. Accordingly, differences in core temperature, even at very low levels, appear critical for optimal protection of the newborn brain during hypothermic circulatory arrest.