A comparison of the effects on neuronal Golgi morphology, assessed with electron microscopy, of cardiopulmonary bypass, low-flow bypass, and circulatory arrest during profound hypothermia.

Adult swine (n = 18) were studied to compare the effects on neuronal morphology of hypothermic circulatory arrest with hypothermic very-low-flow cardiopulmonary bypass. Animals were anesthetized with halothane and prepared in a standard manner for nonpulsatile cardiopulmonary bypass. Monitored variables included mean arterial pressure, arterial blood gases, the processed electroencephalogram, and subdural brain temperature. Bypass was initiated with pump flows of 100 ml.kg-1.min-1, and mean arterial pressure was kept above 50 mm Hg at all times. Animals were cooled to 18 degrees C, using a heat exchanger, and were randomly assigned to one of three groups. Group 1 animals were control animals who underwent 1 hour of hypothermic cardiopulmonary bypass. Group 2 animals underwent 1 hour of circulatory arrest. Group 3 animals underwent 1 hour of very-low-flow cardiopulmonary bypass (10% of normal). At the end of the 1 hour of hypothermic bypass, very-low-flow bypass, or arrest period, animals were rewarmed to 37 degrees C with normal bypass flows, and normothermic perfusion continued for 1 additional hour. Animals were then perfusion fixed with formalin and the brains were removed for electron microscopic analysis. Electron microscopic analysis was used to determine the effects of treatment and was limited to 20 neurons of the CA1 sector of the hippocampus in each animal. Golgi bodies were identified and classified as normal, mildly affected, or severely affected. Animals subjected to either very-low-flow bypass or circulatory arrest had significantly more severely affected and significantly fewer normal Golgi bodies than control animals (p < 0.001). Animals maintained with very-low-flow bypass, however, had significantly more severely affected and fewer normal Golgi bodies than animals subjected to circulatory arrest (p < 0.001). We conclude that under the conditions of this experiment very-low-flow hypothermic cardiopulmonary bypass is associated with significantly greater neuronal Golgi abnormalities than total circulatory arrest.     

Comparison of metabolic responses to deep hypothermic total circulatory arrest and retrograde cerebral perfusion in an experimental model

An experimental study was designed to search the effectiveness of retrograde cerebral perfusion which is presently used as cerebral protection method for the surgery of arcus aorta. Twelve dogs were subjected to the study. Six of them were remained in total circulatory arrest at 20 degrees C for 60 min. Retrograde cerebral perfusion was done again at 20 degrees C for 1 h for the other six dogs.Tumor necrosis factor (TNF), P-selectin, Intracellular Adhesion Molecule (ICAM), Creatine Phosphokinase (CPK-BB) and tissue Adenosine triphosphate (ATP) levels were measured, before the cardiopulmonary bypass at 37 degrees C and during perfusion period at 5, 60 min and 4 h.Tissue ATP level for retrograde cerebral perfusion group was 3.99+/-0.7 mcmol/g tissue and 2.86+/-0.1 mcmol/g tissue for total circulatory arrest group at fourth hour (p<0.05). TNF level was significantly higher in total circulatory arrest group than retrograde cerebral perfusion group (p<0.05). The samples taken at fourth hour of reperfusion showed the TNF level was, 162.55+/-13.1 pcg/ml for total circulatory arrest group and this value was 12.5+/-3.4 pcg/ml for retrograde cerebral perfusion group.ICAM (Intracellular Adhesion Molecule) level was higher in total circulatory arrest group (18.75+/-3.6 ng/ml) when compared to retrograde cerebral perfusion group (8.75+/-1.8 ng/ml) (p<0.05).All parameters showed that retrograde cerebral perfusion preserved the brain functions better comparing with total circulatory arrest. The time necessary for aortic surgery may be provided by the retrograde cerebral perfusion technique.     

The effect of hypothermic cardiopulmonary bypass and total circulatory arrest on cerebral metabolism in neonates, infants, and children

Cardiopulmonary bypass management in neonates, infants, and children often requires the use of deep hypothermia at 18 degrees C with occasional periods of circulatory arrest and represents marked physiologic extremes of temperature and perfusion. The safety of these techniques is largely dependent on the reduction of metabolism, particularly cerebral metabolism. We studied the effect of hypothermia on cerebral metabolism during cardiac surgery and quantified the changes. Cerebral metabolism was measured before, during, and after hypothermic cardiopulmonary bypass in 46 pediatric patients, aged 1 day to 14 years. Patients were grouped on the basis of the different bypass techniques commonly used in children: group A--moderate hypothermic bypass at 28 degrees C; group B--deep hypothermic bypass at 18 degrees to 20 degrees C with maintenance of continuous flow; and group C--deep hypothermic circulatory arrest at 18 degrees C. Cerebral metabolism significantly decreased under hypothermic conditions in all groups compared with control levels at normothermia, the data demonstrating an exponential relationship between temperature and cerebral metabolism and an average temperature coefficient of 3.65. There was no significant difference in the rate of metabolism reduction (temperature coefficient) in patients cooled to 28 degrees and 18 degrees C. From these data we were able to derive an equation that numerically expresses a hypothermic metabolic index, which quantitates duration of brain protection provided by reduction of cerebral metabolism owing to hypothermic bypass over any temperature range. Based on this index, patients cooled to 28 degrees C have a predicted ischemic tolerance of 11 to 19 minutes. The predicted duration that the brain can tolerate ischemia ("safe" period of deep hypothermic circulatory arrest) in patients cooled to 18 degrees C, based on our metabolic index, is 39 to 65 minutes, similar to the safe period of deep hypothermic circulatory arrest known to be tolerated clinically. In groups A and B (no circulatory arrest), cerebral metabolism returned to control in the rewarming phase of bypass and after bypass. In group C (circulatory arrest), cerebral metabolism and oxygen extraction remained significantly reduced during rewarming and after bypass, suggesting disordered cerebral metabolism and oxygen utilization after deep hypothermic circulatory arrest. The results of this study suggest that cerebral metabolism is exponentially related to temperature during hypothermic bypass with a temperature coefficient of 3.65 in neonates infants and children. Deep hypothermic circulatory arrest changes cerebral metabolism and blood flow after the arrest period despite adequate hypothermic suppression of metabolism.     

Brain protection during circulatory arrest

Previous nuclear magnetic resonance studies in this laboratory have shown a beneficial biochemical effect of antegrade cerebroplegia (CP-A) during hypothermic circulatory arrest. This study compared CP-A with other methods of cerebral protection during hypothermic circulatory arrest to assess the clinical utility of this technique. Twenty-three sheep were divided into four groups: systemic hypothermia alone (SYST) and systemic hypothermia combined with external cranial cooling (EXTNL), retrograde cerebroplegia (CP-R), or CP-A. Cardiopulmonary bypass was started, and the sheep were cooled to 15 degrees C and subjected to 2 hours of circulatory arrest. Cardiopulmonary bypass was restarted, and the animals were rewarmed and weaned from cardiopulmonary bypass. Serial neurological examinations were performed and hourly scores assigned until the animals were extubated. Postanesthetic neurological scores improved in all groups throughout the 6-hour recovery period except the CP-R group. The improvement over time for these scores was similar for the EXTNL and CP-A groups and significantly better than for the SYST or CP-R groups (p = 0.004). The CP-A group had 5 of 7 animals with deficit-free survival despite the similarity in recovery of baseline brainstem function. We conclude that both antegrade infusion of cerebroplegia and external cranial cooling confer distinct cerebroprotective effects after a protracted period of hypothermic circulatory arrest when compared with the other methods studied.     

The effects of a leukocyte-depleting filter on cerebral and renal recovery after deep hypothermic circulatory arrest

OBJECTIVE: The purpose of this study was to determine the effects of a leukocyte-depleting filter on cerebral and renal recovery after deep hypothermic circulatory arrest. METHODS: Sixteen 1-week-old piglets underwent cardiopulmonary bypass, were cooled to 18 degrees C, and underwent 60 minutes of circulatory arrest, followed by 60 minutes of reperfusion and rewarming. Global and regional cerebral blood flow, cerebral oxygen metabolism, and renal blood flow were determined before cardiopulmonary bypass, after the institution of cardiopulmonary bypass, and at 1 hour of deep hypothermic circulatory arrest. In the study group (n = 8 piglets), a leukocyte-depleting arterial blood filter was placed in the arterial side of the cardiopulmonary bypass circuit. RESULTS: With cardiopulmonary bypass, no detectable change occurred in the cerebral blood flow, cerebral oxygen metabolism, and renal blood flow in either group, compared with before cardiopulmonary bypass. In control animals, after deep hypothermic circulatory arrest, blood flow was reduced to all regions of the brain (P <.004) and the kidneys (P =.02), compared with before deep hypothermic circulatory arrest. Cerebral oxygen metabolism was also significantly reduced to 60.1% +/- 11.3% of the value before deep hypothermic circulatory arrest (P =.001). In the leukocyte-depleting filter group, the regional cerebral blood flow after deep hypothermic circulatory arrest was reduced, compared with the value before deep hypothermic circulatory arrest (P <.01). Percentage recovery of cerebral blood flow was higher in the leukocyte filter group than in the control animals in all regions but not significantly so (P >.1). The cerebral oxygen metabolism fell to 66.0% +/- 22.3% of the level before deep hypothermic circulatory arrest, which was greater than the recovery in the control animals but not significantly so (P =.5). After deep hypothermic circulatory arrest, the renal blood flow fell to 81.0% +/- 29.5% of the value before deep hypothermic circulatory arrest (P =.06). Improvement in renal blood flow in the leukocyte filter group was not significantly greater than the recovery to 70.2% +/- 26.3% in control animals (P =.47). CONCLUSIONS: After a period of deep hypothermic circulatory arrest, there is a significant reduction in cerebral blood flow, cerebral oxygen metabolism, and renal blood flow. Leukocyte depletion with an in-line arterial filter does not appear to significantly improve these findings in the neonatal piglet.     

Poloxamer 188 improves neurologic outcome after hypothermic circulatory arrest.

Poloxamer 188, an amphipathic copolymer with cytoprotective properties, was investigated as a means of improving neurologic outcome after a prolonged period (150 minutes) of deep hypothermic circulatory arrest. Dogs were perfusion cooled and surface cooled to 10 degrees C, the heart was arrested for 150 minutes, and then the dogs were rewarmed and weaned from bypass. Seven dogs were treated with poloxamer 188 before and after deep hypothermic circulatory arrest. Six control dogs were treated with saline. Surviving dogs were evaluated for 1 week after deep hypothermic circulatory arrest for neurologic deficits or behavioral changes. Neurologic outcome was graded by the following system: grade 1, death within the observation period; grade 2, comatose; grade 3, holds head up; grade 4, sits up; grade 5, stands; grade 6, normal in both behavior and gait. There were no deaths in the seven poloxamer 188-treated animals versus three deaths in the six control dogs. Poloxamer 188-treated dogs also manifested significantly less neurologic dysfunction after deep hypothermic circulatory arrest than did the control group (p less than 0.003). This study shows that poloxamer 188 has a significant impact in improving neurologic outcome after exceptionally long periods of deep hypothermic circulatory arrest.     

Low-flow hypothermic cardiopulmonary bypass protects the brain

Cerebral protection during surgical procedures necessitating circulatory arrest or low flow remains the factor that most limits the critical time for repair of lesions. In vivo phosphorus-31 nuclear magnetic resonance spectroscopy was used to assess the metabolic state of the brain during circulatory arrest by measuring the concentration of high-energy phosphate compounds and the intracellular pH. The degree of cerebral protection during deep hypothermic cardiopulmonary bypass at low flow rates was compared with that obtained with a period of circulatory arrest interrupted by intermittent systemic perfusion. Sheep were instrumented with cannulas for cardiopulmonary bypass, and a radiofrequency coil was positioned on the skull. Animals were placed in the bore of a 4.7 Tesla magnet, cooled with the aid of cardiopulmonary bypass to 15 degrees C, and had either circulatory arrest (n = 5) or continuous low flow rates of 5 ml/kg/min (n = 6) or 10 ml/kg/min (n = 7) for 2 hours. A fourth group (n = 5) underwent 1 hour of circulatory arrest, systemic reperfusion for 30 minutes, then another hour of circulatory arrest. Both circulatory arrest and a flow rate of 5 ml/kg/min resulted in severe intracellular acidosis and depletion of high-energy phosphates. A flow of 10 ml/kg/min preserved high-energy phosphates and intracellular pH. Therefore deep hypothermia with cardiopulmonary bypass flows as low as 10 ml/kg/min can maintain brain high-energy phosphate concentrations and intracellular pH for 2 hours in sheep, whereas flows of 5 ml/kg/min or intermittent full-flow systemic perfusion between periods of circulatory arrest offers less protection. Previous studies from our laboratory have shown that improvement in nuclear magnetic resonance parameters positively correlates with improved survival and preservation of neurologic function.     

Cold cerebroplegia. A new technique of cerebral protection during operations on the transverse aortic arch

Profound hypothermia associated with circulatory arrest is the commonest method of cerebral protection during operations on the aortic arch. This technique allows a limited time to perform the aortic repair, however. It also necessitates prolonged cardiopulmonary bypass to rewarm the patient. This may be the cause of coagulation disorders or infection. Selective perfusion of the carotid arteries can also be used. When the perfusion is derived from the main arterial line, however, the repair of the aorta requires that the vessel be crossclamped, and cannot be performed in an "open, bloodless" manner. To avoid the disadvantages of both techniques, we have developed a new technique of cerebral protection. After a regular cardiopulmonary bypass has been established, the carotid arteries are cannulated and perfused with blood cooled at 6 degrees to 12 degrees C, through a separate heat exchanger, while the core temperature is maintained at moderate hypothermia (25 degrees to 28 degrees C, rectal). To perform the "open" distal repair, the cardiopulmonary bypass is discontinued while the carotid perfusion is maintained (250 to 350 ml/min). When the distal repair is completed, cardiopulmonary bypass is resumed and the carotid perfusion is discontinued. Between 1984 and June 1989, 54 patients (mean age 55 years) were operated on with this method (45 elective operations, 9 emergency procedures). Mean duration of cardiopulmonary bypass was 121 minutes (65 to 248), and mean duration of circulatory arrest was 22 minutes (10 to 51). The electroencephalogram, routinely recorded, showed return of the cerebral activity after a mean time of 12 minutes and normal activity after a mean time of 66 minutes. There was no intraoperative death. Hospital mortality rate was 13% (7/54). One death was related to neurologic disorders. All patients but one awakened normally within 8 hours after operation. Two patients (4.3%) experienced a transient neurologic episode (lateral hemianopia) 9 and 11 days postoperatively. There was no hemorrhagic complication (24-hour average blood loss: 840 +/- 540 ml). In our experience the technique of "cold cerebroplegia" has been demonstrated to provide excellent cerebral protection. It requires no prolonged cardiopulmonary bypass and does not limit the time necessary to perform the aortic repair. It may be considered as a safe alternative to profound hypothermia associated with circulatory arrest.     

Hippocampal neuronal death following deep hypothermic circulatory arrest in dogs: involvement of apoptosis.

This study was undertaken to evaluate the histological nature of brain damage caused by deep hypothermic circulatory arrest during cardiopulmonary bypass. Total body cooling to 15 degrees C and rewarming were performed with a conventional cardiopulmonary bypass technique using the femoral artery and vein. Dogs were assigned to one of three groups. In group 1 (n = 4), cardiopulmonary bypass was maintained in a state of deep hypothermia (15 degrees C) for 90 min, group 2 animals (n = 5) underwent 60 min of deep hypothermic circulatory arrest at 15 degrees C, and group 3 (n = 6) underwent 90 min of deep hypothermic circulatory arrest at 15 degrees C. All dogs were killed by perfusion fixation 72 h after cardiopulmonary bypass. The CA1 regions of the hippocampi were examined by light and electron microscopy. Biotinylated dUTP was used for nick-end labeling of apoptotic cells mediated by terminal deoxytransferase. No morphological change was observed in group 1 dogs, and very little in group 2 dogs. More severe neuronal damage was observed in group 3. The nuclei of many cells were shrunken and showed nick-end labeling. Dense chromatin masses were detected electron microscopically in the nuclei of CA1 pyramidal cells. Neuronal cell death observed in CA1 pyramidal cells 72 h after 90 min of deep hypothermic circulatory arrest at 15 degrees C involves apoptosis. Therefore, according to this model, the maximum duration of deep hypothermic circulatory arrest should not be allowed to exceed 60 min.     

The effects of deep hypothermic cardiopulmonary bypass and total circulatory arrest on cerebral blood flow in infants and children

Cardiopulmonary bypass management in infants and children involves extensive alterations in temperature, hemodilution, and perfusion pressure, with occasional periods of circulatory arrest. Despite the use of these biologic extremes of temperature and perfusion, their effects on cerebral blood flow are unknown. This study was designed to examine the relationship of mean arterial pressure and nasopharyngeal temperature to cerebral blood flow during deep hypothermic cardiopulmonary bypass (18 degrees to 22 degrees C) with and without periods of total circulatory arrest. Cerebral blood flow was measured before, during, and after deep hypothermic cardiopulmonary bypass using xenon clearance techniques in 25 children, aged 2 days to 60 months. Fourteen patients underwent repair with circulatory arrest. There was a highly significant correlation of cerebral blood flow with temperature during cardiopulmonary bypass (p = 0.007). During deep hypothermic bypass there was a significant association between cerebral blood flow and mean arterial pressure (p = 0.027). In infants undergoing repair with deep hypothermia alone, cerebral blood flow returned to prebypass levels in the rewarming phase of bypass. However, in patients undergoing repair with circulatory arrest, no significant increase in cerebral blood flow during rewarming or even after bypass was observed (p = 0.01). These data show that deep hypothermic cardiopulmonary bypass significantly decreases cerebral blood flow because of temperature reduction. Under conditions of deep hypothermia, cerebral pressure-flow autoregulation is lost. This study also demonstrates that cerebral reperfusion after deep hypothermia is impaired if the patient is exposed to a period of total circulatory arrest.     

Kinetics of cerebral deoxygenation during deep hypothermic circulatory arrest in neonates.

Brain injury associated with neonatal congenital heart operations performed during deep hypothermia and/or total circulatory arrest is often attributed to cerebral hypoxia. We studied the kinetic changes in cerebrovascular hemoglobin O2 saturation (HbO2%) and total hemoglobin concentration (Hbtotal) in 17 neonates undergoing cardiac surgery as they were cooled to 15 degrees C, underwent total circulatory arrest, and were rewarmed. HbO2% and Hbtotal in brain vasculature were monitored noninvasively by near-infrared spectroscopy. Neonates were cooled over 12 min and rewarmed over 15 min while being perfused using cardiopulmonary bypass (CPB). Total circulatory arrest lasted from 20 to 70 min. We found that HbO2% in brain vasculature increased during the initial 8 min of CPB as nasopharyngeal temperature decreased, and then remained constant until circulatory arrest. After the onset of circulatory arrest, cerebrovascular HbO2% decreased curvilinearly for 40 min; no further hemoglobin desaturation was observed from 40 to 70 min of arrest. The changes in cerebrovascular Hbtotal were quite different from those in HbO2%, as Hbtotal decreased during the initial minute of CPB and circulatory arrest and then remained constant until recirculation. Brain intravascular HbO2% and Hbtotal increased within 3 min after the onset of recirculation to prearrest levels, and during rewarming, HbO2% decreased to normothermic baseline values. The results demonstrate that cerebral oxygenation increased during CPB cooling; O2 was consumed by the neonatal brain during the initial 40 min of deep hypothermic circulatory arrest; and cerebral oxygenation was restored on recirculation. These observations may be important in identifying the etiologies of brain injury during neonatal congenital heart surgery.     

Barbiturates impair cerebral metabolism during hypothermic circulatory arrest.

Barbiturates have been used as a method of cerebral protection in patients undergoing open heart operations. Phosphorus 31 nuclear magnetic resonance spectroscopy was used to assess barbiturate-induced alterations in the cerebral tissue energy state during cardiopulmonary bypass, hypothermic circulatory arrest, and subsequent reperfusion. Sheep were positioned in a 4.7-T magnet with a radiofrequency coil over the skull. Nuclear magnetic resonance spectra were obtained at 37 degrees C, during cardiopulmonary bypass before and after drug administration at 37 degrees C and 15 degrees C, throughout a 1-hour period of hypothermic circulatory arrest, and during a 2-hour reperfusion period. A group of animals (n = 8) was administered a bolus of sodium thiopental (40 mg/kg) during bypass at 37 degrees C followed by an infusion of 3.3 mg.kg-1 x min-1 until hypothermic arrest. A control group of animals (n = 8) received no barbiturate. The phosphocreatine/adenosine triphosphate ratio, reflecting tissue energy state, was lower during cardiopulmonary bypass at 15 degrees C in the treated animals compared with controls (1.06 +/- 0.08 versus 1.36 +/- 0.17; p < 0.001). Lower phosphocreatine/adenosine triphosphate ratios were observed throughout all periods of arrest and reperfusion in the barbiturate-treated animals compared with controls (p < or = 0.01). Thiopental prevented the increase in cerebral energy state normally observed with hypothermia and resulted in a decrease in the energy state of the brain during hypothermic circulatory arrest and subsequent reperfusion. These results suggest that thiopental administration before a period of hypothermic circulatory arrest may prove detrimental to the preservation of the energy state of the brain.     

Power spectral analysis of EEG during simple deep hypothermia under ether anesthesia

Power spectral analysis of electroencephalogram was performed during simple deep hypothermia under ether anesthesia, compared with that during hypothermic cardiopulmonary bypass under morphine anesthesia. In ether anesthesia group, EEG isoelectricity developed at average esophageal temperature of 27.2 degrees C which is higher than the temperature previously reported. This remarkable depression of the EEG may be due to deep ether anesthesia, because severe hypotension episodes were not associated with this and no neurological complication was noticed post-operatively. In cardiopulmonary bypass group, EEG activity persisted throughout the procedures even at the lowest esophageal temperature reached of 22.3 degrees C. In ether anesthesia group, the temperature at which EEG activity reappeared correlated with the duration of circulatory arrest. During simple deep hypothermia under ether anesthesia, the EEG is not useful to detect brain ischemia during cooling period, because EEG activity was lost in the early course of cooling, but during rewarming period the EEG demonstrated depression of cerebral function due to total circulatory arrest.     

A novel protocol of retrograde cerebral perfusion with intermittent pressure augmentation for brain protection

OBJECTIVES: We examined a novel protocol of retrograde cerebral perfusion with intermittent pressure augmentation to improve the clinical usefulness of this procedure, in a canine model, because a high retrograde cerebral perfusion pressure may be required to open cerebral vessels. METHODS: Eighteen dogs (25.2 +/- 4.1 kg) were randomly divided into the following 3 groups: circulatory arrest group (circulatory arrest alone), conventional-retrograde cerebral perfusion group (conventional retrograde cerebral perfusion at 25 mm Hg), and intermittent-retrograde cerebral perfusion group (retrograde cerebral perfusion at 15 mm Hg with intermittent pressure augmentation to 45 mm Hg). The animals were cooled down to 26 degrees C under cardiopulmonary bypass and underwent 60 minutes of circulatory arrest with or without retrograde cerebral perfusion in accordance with the protocol described. They were weaned from cardiopulmonary bypass after rewarming and observed for 12 hours after the procedures. The retinal vessels were observed as a means of noninvasive direct visualization of the cerebral vascular system. The level of Tau proteins in the cerebrospinal fluid was measured as a marker of neuronal damage. RESULTS: While the retinal vessels were fully distended with blood (100%) at a retrograde cerebral perfusion pressure of 45 mm Hg in the intermittent-retrograde cerebral perfusion group, full distension of the retinal vessels was not observed in the conventional-retrograde cerebral perfusion group (67%). The level of Tau proteins, measured 12 hours after the operation, was lower in the intermittent-retrograde cerebral perfusion group (247 +/- 70 pg/mL) than in the circulatory arrest group (1313 +/- 463 pg/mL; P < .05) or the conventional-retrograde cerebral perfusion group (1449 +/- 693 pg/mL; P < .05). Histopathologic examination revealed that the most effective brain protection was obtained in the intermittent-retrograde cerebral perfusion group (P < .05). CONCLUSIONS: Intermittent-retrograde cerebral perfusion effectively opens up cerebral vessels to allow adequate blood supply to the brain, thereby minimizing brain damage. This novel method may protect the cerebral system effectively from ischemia during circulatory arrest.     

Deep hypothermic circulatory arrest for hemiarch replacement in a pediatric patient with moyamoya disease

Moyamoya disease is a chronic cerebrovascular occlusive disease, occurring predominantly in young populations, that causes cerebral ischemia and hemorrhage. Patients with moyamoya disease are at high risk of neurological complications during cardiac surgery because of perioperative hemodynamic changes. However, there is no established evidence on temperature management during cardiopulmonary bypass. Previous reports described normothermia or mild to moderate hypothermia during cardiopulmonary bypass in patients with moyamoya disease; however, surgical conditions, such as not having enough space to clamp the aorta or a clean surgical field, sometimes force us to use deep hypothermic circuratory arrest. We report a successful case of a pediatric patient with moyamoya disease who underwent deep hypothermic circulatory arrest (18 °C) for hemiarch replacement without neurological complications. Deep hypothermia may be an alternative technique for achieving cerebral protection in the context of moyamoya disease.     

Physiologic effects of deep hypothermia and microwave rewarming: possible application for neonatal cardiac surgery

Deep hypothermia (20 C) without cardiopulmonary bypass is a valuable technique during cardiac surgery in infants but rewarming of the heart following circulatory arrest and cardiac repair has traditionally been a lengthy and difficult process. In experimental animals rewarming the heart with microwave energy, as reported in this work, warms the heart before warming the periphery. In 18 mongrel dogs that were surface cooled to 20 C, we found that during microwave rewarming the core temperature rose 4.7 C per hour. Whole body oxygen consumption, heart rate, and cardiac output returned to normal at rates equal to the rates at which they decreased during surface cooling. Blood pressure and arterial gases remained adequate. Microwave rewarming appears to be a useful method for reestablishment of cardiac function and normothermia following deep hypothermia.     

Hyperglycemia increases cerebral intracellular acidosis during circulatory arrest.

Phosphorus 31 nuclear magnetic resonance spectroscopy was used to assess cerebral high-energy phosphate metabolism and intracellular pH in normoglycemic and hyperglycemic sheep during hypothermic circulatory arrest. Two groups of sheep (n = 8 per group) were placed in a 4.7-T magnet and cooled to 15 degrees C using cardiopulmonary bypass. Spectra were acquired before and during circulatory arrest and during reperfusion and rewarming. Intracellular pH and adenosine triphosphate levels decreased during circulatory arrest. Compared with the normoglycemic animals, the hyperglycemic group was significantly more acidotic with the greatest difference observed during the first 20 minutes of reperfusion (6.40 +/- 0.08 versus 6.08 +/- 0.06; p < 0.001). Intracellular pH returned to baseline after 30 minutes of reperfusion in the normoglycemic group but did not reach baseline until 1 hour of reperfusion in the hyperglycemic animals. Adenosine triphosphate levels were significantly higher in the hyperglycemic group during circulatory arrest. Repletion of adenosine triphosphate during reperfusion was similar for both groups. These results support the hypothesis that hyperglycemia during cerebral ischemia drives anaerobic glycolysis and thus leads to increased lactate production and an increase [corrected] in the intracellular acidosis normally associated with ischemia.     

Neuropsychometric outcome following aortic arch surgery: a prospective randomized trial of retrograde cerebral perfusion

BACKGROUND: Aortic surgery requiring hypothermic circulatory arrest is associated with a high incidence of brain injury. However, knowledge of neuropsychometric outcome is limited. Retrograde cerebral perfusion has become a popular adjunctive technique to hypothermic circulatory arrest. The aim of this study was to assess neuropsychometric outcome and compare the 2 techniques. METHODS: In a prospective randomized trial, 38 patients requiring elective aortic arch surgery were allocated to either hypothermic circulatory arrest plus retrograde cerebral perfusion or hypothermic circulatory arrest alone. Neuropsychometric testing was performed preoperatively, and at 6 weeks and 12 to 24 weeks postoperatively. Deficit was defined as a 20% decline in 2 tests or more. Standardized Z scores were calculated for each patient and test. Eighteen patients underwent hypothermic circulatory arrest and 20 patients underwent hypothermic circulatory arrest plus retrograde cerebral perfusion. The mean cardiopulmonary bypass, hypothermic circulatory arrest, and retrograde cerebral perfusion durations were 169, 30, and 25 minutes, respectively. RESULTS: There were 2 deaths and 2 neurological deficits. At 6 weeks postoperatively, 77% of the hypothermic circulatory arrest group and 93% of the hypothermic circulatory arrest plus retrograde cerebral perfusion group had a deficit (P =.22). At 12 weeks this was reduced to 55% and 56%, respectively (P =.93). There was a worse total Z test score in the hypothermic circulatory arrest plus retrograde cerebral perfusion group at 12 weeks (P =.05). Neuropsychometric change did not correlate with hypothermic circulatory arrest duration, presence of aortic atheroma, cannulation technique, or procedure. CONCLUSIONS: Hypothermic circulatory arrest plus/minus retrograde cerebral perfusion is associated with a high incidence of neuropsychometric change despite ostensibly normal clinical outcomes and apparently safe arrest duration. Retrograde cerebral perfusion did not improve outcome in this small study.     

The effects of cardiopulmonary bypass and profound hypothermic circulatory arrest on anterior fontanel pressure in infants

The Ladd transducer was used to measure anterior fontanel pressure in 23 infants undergoing cardiopulmonary bypass and profound hypothermic circulatory arrest for surgical correction of congenital heart disease. Mean (+/- SD) minimum oesophageal and rectal temperatures of 11.3 +/- 1.5 degrees C and 18.1 +/- 2.2 degrees C respectively were achieved with a mean duration of arrest of 53.4 +/- 13.9 minutes. During reperfusion cardiopulmonary bypass after circulatory arrest, mean anterior fontanel pressure (18.3 +/- 6.4 mmHg) increased above baseline pre-bypass values (10.6 +/- 2.9 mmHg) (p less than 0.005). Mean arterial blood pressure decreased significantly from pre-bypass values (57.0 +/- 11.8 mmHg) during both cooling (38.8 +/- 8.4 mmHg) and rewarming cardiopulmonary bypass (45.8 +/- 8.9 mmHg) (p less than 0.005). These changes were associated with a significant decrease in cerebral perfusion pressure during cooling (27.3 +/- 11.0 mmHg) and rewarming cardiopulmonary bypass (27.5 +/- 10.6 mmHg), compared with baseline pre-bypass values (46.5 +/- 12.3 mmHg) (p less than 0.005). The data demonstrate significant but transient decreases in cerebral perfusion pressure during cooling and rewarming bypass.     

Profound hypothermia (less than 10 degrees C) compared with deep hypothermia (15 degrees C) improves neurologic outcome in dogs after two hours' circulatory arrest induced to enable resuscitative surgery

Deaths from uncontrollable hemorrhage might be prevented by arresting the circulation under protective hypothermia to allow resuscitative surgery to repair these injuries in a bloodless field. We have shown previously that in hemorrhagic shock, circulatory arrest of 60 minutes under deep hypothermia (tympanic membrane temperature, Ttm = 15 degrees C) was the maximum duration of arrest that allowed normal brain recovery. We hypothesize that profound cerebral hypothermia (Ttm less than 10 degrees C) could extend the duration of safe circulatory arrest. In pilot experiments, we found that the cardiopulmonary system did not tolerate arrest at a core (esophageal) temperature (Tes) of less than 10 degrees C. Twenty-two dogs underwent 30-minute hemorrhagic shock (mean arterial pressure 40 mm Hg), rapid cooling by cardiopulmonary bypass (CPB), blood washout to a hematocrit of less than 10%, and circulatory arrest of 2 hours. In deep hypothermia group 1 (n = 10), Ttm was maintained at 15 degrees C during arrest. In profound hypothermia group 2 (n = 12), during cooling with CPB, the head was immersed in ice water, which decreased Ttm to 4 degrees-7 degrees C. The Tes was 10 degrees C in all dogs during arrest. Reperfusion and rewarming were by CPB for 2 hours. Controlled ventilation was to 24 hours, intensive care to 72 hours. In the 20 dogs that followed protocol, best neurologic deficit scores (0% = normal, 100% = brain death) at 24-72 hours were 23% +/- 19% in group 1 and 12% +/- 8% in group 2 (p = 0.15). Overall performance categories and histologic damage scores were significantly better in group 2 (p = 0.04 and p less than 0.001, respectively). We conclude that profound cerebral hypothermia with CPB plus ice water immersion of the head can extend the brain's tolerance of therapeutic circulatory arrest beyond that achieved with deep hypothermia.