Isolated Cerebral Hypothermia by Single Carotid Artery Perfusion of Extracorporeally Cooled Blood in Baboons

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Abstract
Hypothermia has been demonstrated to protect the brain from ischemic or traumatic injury. Previous efforts to induce cerebral hypothermia have relied on techniques requiring total body cooling that have resulted in serious cardiovascular derangements. A technique to selectively cool the brain, without systemic hypothermia, may have applications for the treatment of neurological disease. After induction of general anesthesia in 12 baboons, the right common carotid artery and ipsilateral femoral artery were each occlusively cannulated and joined to a centrifugal pump. In a closed-circuit system, blood was continually withdrawn from the femoral artery, cooled by water bath, and infused through the common carotid artery with its external branches occluded. Pump flow was varied so that right carotid pressure approximated systemic blood pressure. In six animals, perfusate was cooled to decrease right cerebral temperature to < 19 degrees C for 30 minutes. In six animals, right cerebral temperature was decreased to < 25 degrees C for 3 hours. In those six animals, 133Xe was injected into the right carotid artery before, during, and after hypothermia. Peak radioactivity and washout curves were recorded from bilateral cranial detectors. Systemic warming was accomplished by convective air and warm water blankets. Esophageal, rectal, and bilateral cerebral temperatures were continuously recorded. In animals cooled to < 19 degrees C, right cerebral temperature decreased from 34 degrees C to 18.5 +/- 1.1 degrees C (mean +/- standard deviation), P < 0.01, in 26 +/- 13 minutes. Simultaneously, left cerebral temperature decreased to 20.7 +/- 1.6 degrees C. During 30 minutes of stable cerebral hypothermia, esophageal temperature decreased from 35.1 +/- 2.3 degrees C to 34.2 +/- 2.2 degrees C, P < 0.05. In animals cooled to < 25 degrees C, right cerebral temperature decreased from 34 degrees C to 24.5 +/- 0.6 degrees C in 12.0 +/- 6.0 minutes, P < 0.01. Simultaneously, left cerebral temperature decreased to 26.3 +/- 4.8 degrees C. After 3 hours of stable cerebral hypothermia, esophageal temperature was 34.4 +/- 0.5 degrees C, P < 0.05. Right hemispheric cerebral blood flow decreased during hypothermia (26 +/- 16 ml/min/100 g) compared to values before and after hypothermia (63 +/- 29 and 51 +/- 34 ml/min/100 g, respectively; P < 0.05). Furthermore, hypothermic perfusion resulted in a proportionally increased radioactivity peak detected in the left cerebral hemisphere after right carotid artery injection of 133Xe (0.8 +/- 0.2:1, left:right) compared to normothermia before and after hypothermia (0.3 +/- 2 and 0.3 +/- 1, respectively; P < 0.05). Normal heart rhythm, systemic arterial blood pressure, and arterial blood gas values were preserved during hypothermia in all animals. Bilateral cerebral deep or moderate hypothermia can be induced by selective perfusion of a single internal carotid artery, with minimal systemic cooling and without cardiovascular instability. This global brain hypothermia results from profoundly altered collateral cerebral circulation during artificial hypothermic perfusion. This technique may have clinical applications for neurosurgery, stroke, or traumatic brain injury.