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

Dennis J. Mujsce, Javad Towfighi, Daniel F. Heitjan, Robert C. Vannucci

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

Abstract

Background and Purpose Hypothermia to core temperatures ranging from 16°C to 24°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 hypothermie 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°C (n=6), 20°C (n=8), or 24°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°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°C and the least damage to this structure at 16°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°C compared with 20°C but with no difference in the severity of damage between 20°C and 16°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 hypothermie circulatory arrest influence the severity of damage to the cerebral cortex of newborn dogs. Specifically, the lower the temperature below 24°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 hypothermie circulatory arrest.

Original languageEnglish (US)
Pages (from-to)1433-1441
Number of pages9
JournalStroke
Volume25
Issue number7
DOIs
StatePublished - Jul 1994

Keywords

  • Dogs
  • Heart arrest
  • Hypothermia
  • Newborn

ASJC Scopus subject areas

  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine
  • Advanced and Specialized Nursing

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