Cerebral air emboli differentially alter outcome after cardiopulmonary bypass in rats compared with normal circulation

BACKGROUND: Cerebral air emboli (CAE) are thought to contribute to adverse cerebral outcomes following cardiac surgery with cardiopulmonary bypass (CPB). This study was designed to investigate the effect of escalating volumes of CAE on survival and neurologic and histologic outcomes. In addition, the effect of xenon administration during CAE on these outcomes was determined. METHODS: With institutional review board approval, four groups were studied (n = 15). In two CPB-CAE groups, rats were subjected to 90 min CPB with 10 repetitively administered CAE. Rats in two sham-CAE groups were also exposed to CAE but not to CPB. Rats were randomly assigned to sequential dose cohorts receiving CAE ranging from 0.2 to 10 microl in a dose-escalating fashion. Groups were further subdivided into xenon (56%) and nitrogen groups. Rats with severe neurologic damage were killed; others were neurologically tested until postoperative day 7, when infarct volumes were determined. Survival and neurologic and histologic outcomes were tested with logistic regression analyses (P < 0.05). RESULTS: This study demonstrates a dose-dependent relation between CAE volumes and survival, neurologic outcome, and histologic outcome. For all outcomes, CPB adversely affected the dose-effect curves compared with sham-CAE groups (P < 0.05). Xenon demonstrated no impact on either outcome. CONCLUSIONS: This study describes the successful incorporation of CAE in a rodent CPB model and allows identifying suitable CAE volumes for subsequent studies. CAE exhibit a differential effect on outcome in rats undergoing CPB versus those not exposed to CPB. Perioperative administration of xenon remained without any effect on outcome.     

Xenon Impairs Neurocognitive and Histologic Outcome after Cardiopulmonary Bypass Combined with Cerebral Air Embolism in Rats

Background: The neuroprotective properties of xenon may improve cerebral outcome after cardiac surgery using cardiopulmonary bypass (CPB). However, its disposition to expand gaseous bubbles that during CPB present as cerebral air emboli (CAE) could abolish any beneficial effect or even worsen cerebral outcome. Therefore, the authors studied the impact of xenon on neurologic, cognitive, and histologic outcome after CPB combined with CAE in rats.

Methods: With institutional review board approval, 40 rats were assigned to four groups (n = 10). In two CPB-CAE groups, rats were subjected to 90 min of normothermic CPB with 10 repetitively administered CAEs (0.3 [mu]l/bolus). Rats in two sham groups were not exposed to CPB and CAE. Groups were further subdivided into xenon (56%; 20 min before, during, and 30 min after CPB) and nitrogen groups. Neurologic and cognitive function was tested until postoperative day 14, when cerebral infarct volumes were determined.

Results: Animals of the CPB-CAE groups showed transient deficits in gross neurologic function. Further, rats of the CPB-CAE-xenon group demonstrated impaired fine motor and cognitive performance persisting until postoperative day 14. Consistently, infarct volumes were larger in the CPB-CAE-xenon group compared with the CPB-CAE-nitrogen group (P = 0.03).     

Xenon impairs neurocognitive and histologic outcome after cardiopulmonary bypass combined with cerebral air embolism in rats

BACKGROUND: The neuroprotective properties of xenon may improve cerebral outcome after cardiac surgery using cardiopulmonary bypass (CPB). However, its disposition to expand gaseous bubbles that during CPB present as cerebral air emboli (CAE) could abolish any beneficial effect or even worsen cerebral outcome. Therefore, the authors studied the impact of xenon on neurologic, cognitive, and histologic outcome after CPB combined with CAE in rats. METHODS: With institutional review board approval, 40 rats were assigned to four groups (n = 10). In two CPB-CAE groups, rats were subjected to 90 min of normothermic CPB with 10 repetitively administered CAEs (0.3 microl/bolus). Rats in two sham groups were not exposed to CPB and CAE. Groups were further subdivided into xenon (56%; 20 min before, during, and 30 min after CPB) and nitrogen groups. Neurologic and cognitive function was tested until postoperative day 14, when cerebral infarct volumes were determined. RESULTS: Animals of the CPB-CAE groups showed transient deficits in gross neurologic function. Further, rats of the CPB-CAE-xenon group demonstrated impaired fine motor and cognitive performance persisting until postoperative day 14. Consistently, infarct volumes were larger in the CPB-CAE-xenon group compared with the CPB-CAE-nitrogen group (P = 0.03). CONCLUSIONS: This is the first demonstration in which the neurologic effects of CAE have been examined in a rat model of CPB. Xenon exposure aggravated the neurologic dysfunction that is produced by CAE during CPB; potential neuroprotective effects of xenon may have been masked by the effects of xenon on CAE.     

Xenon Attenuates Cardiopulmonary Bypass-induced Neurologic and Neurocognitive Dysfunction in the Rat

Background: With clinical data suggesting a role for excitatory amino acid neurotransmission in the pathogenesis of cardiopulmonary bypass (CPB)-associated brain injury, the current study was designed to determine whether xenon, an N-methyl-d-aspartate receptor antagonist, would attenuate CPB-induced neurologic and neurocognitive dysfunction in the rat.

Methods: Following surgical preparation, rats were randomly divided into four groups: (1) sham rats were cannulated but did not undergo CPB; (2) CPB rats were subjected to 60 min of CPB using a membrane oxygenator receiving a gas mixture of 30% O2, 65% N2, and 5% CO2; (3) CPB + MK801 rats received MK801 (0.15 mg/kg intravenous) 15 min prior to 60 min of CPB with the same gas mixture; and (4) CPB + xenon rats underwent 60 min of CPB using an oxygenator receiving 30% O2, 60% xenon, 5% N2, and 5% CO2. Following CPB, the rats recovered for 12 days, during which they underwent standardized neurologic and neurocognitive testing (Morris water maze).

Results: The sham and CPB + xenon groups had significantly better neurologic outcome compared to both the CPB and CPB + MK801 groups on postoperative days 1 and 3 (P < 0.05). Compared to the CPB group, the sham, CPB + MK801, and CPB + xenon groups had better neurocognitive outcome on postoperative days 3 and 4 (P < 0.001). By the 12th day, the neurocognitive outcome remained significantly better in the CPB + xenon group compared to the CPB group (P < 0.01).     

Xenon attenuates cardiopulmonary bypass-induced neurologic and neurocognitive dysfunction in the rat

BACKGROUND: With clinical data suggesting a role for excitatory amino acid neurotransmission in the pathogenesis of cardiopulmonary bypass (CPB)-associated brain injury, the current study was designed to determine whether xenon, an N-methyl-D-aspartate receptor antagonist, would attenuate CPB-induced neurologic and neurocognitive dysfunction in the rat. METHODS: Following surgical preparation, rats were randomly divided into four groups: (1) sham rats were cannulated but did not undergo CPB; (2) CPB rats were subjected to 60 min of CPB using a membrane oxygenator receiving a gas mixture of 30% O2, 65% N2, and 5% CO2; (3) CPB + MK801 rats received MK801 (0.15 mg/kg intravenous) 15 min prior to 60 min of CPB with the same gas mixture; and (4) CPB + xenon rats underwent 60 min of CPB using an oxygenator receiving 30% O2, 60% xenon, 5% N2, and 5% CO2. Following CPB, the rats recovered for 12 days, during which they underwent standardized neurologic and neurocognitive testing (Morris water maze). RESULTS: The sham and CPB + xenon groups had significantly better neurologic outcome compared to both the CPB and CPB + MK801 groups on postoperative days 1 and 3 (P < 0.05). Compared to the CPB group, the sham, CPB + MK801, and CPB + xenon groups had better neurocognitive outcome on postoperative days 3 and 4 (P < 0.001). By the 12th day, the neurocognitive outcome remained significantly better in the CPB + xenon group compared to the CPB group (P < 0.01). CONCLUSION: These data indicate that CPB-induced neurologic and neurocognitive dysfunction can be attenuated by the administration of xenon, potentially related to its neuroprotective effect via N-methyl-D-aspartate receptor antagonism.     

Cardiopulmonary Bypass Induces Neurologic and Neurocognitive Dysfunction in the Rat

Background : Neurocognitive dysfunction is a common complication of cardiac surgery using cardiopulmonary bypass (CPB). Elucidating injury mechanisms and developing neuroprotective strategies have been hampered by the lack of a suitable long-term recovery model of CPB. The purpose of this study was to investigate neurologic and neurocognitive outcome after CPB in a recovery model of CPB in the rat.

Methods : Fasted rats (n = 10) were subjected to 60 min of normothermic (37.5[degrees]C) nonpulsatile CPB using a roller pump and a membrane oxygenator. Sham-operated controls (n = 10) were not subjected to CPB. Neurologic outcome was assessed on days 1, 3, and 12 after CPB using standardized functional testing. Neurocognitive outcome, defined as the time (or latency) to finding a submerged platform in a Morris water maze (an indicator of visual-spatial learning and memory), was evaluated daily from post-CPB days 3-12. Histologic injury in the hippocampus was also evaluated.

Results : Neurologic outcome was worse in the CPB versus the sham-operated controls at all three measurement intervals (P < 0.001). The CPB group also had longer water maze latencies compared with the sham-operated controls (P = 0.004), indicating significant neurocognitive dysfunction after CPB. No difference in histologic injury between groups was observed.     

Desflurane Confers Neurologic Protection for Deep Hypothermic Circulatory Arrest in Newborn Pigs

Background: Cardiopulmonary bypass (CPB) and deep hypothermic circulatory arrest (DHCA), as used for infant heart surgery, carry a risk of ischemic neurologic injury. Volatile anesthetics have neuroprotective properties against both global and focal ischemia at normothermia. The authors examined the hemodynamic and neuroprotective effects of desflurane in a piglet CPB-DHCA model.

Methods: Twenty piglets aged 5-10 days received a desflurane- (6-9% expired) or fentanyl-based anesthetic before and during CPB (before and after DHCA). DHCA lasted 90 min at 19[degrees]C brain. Cardiovascular variables (heart rate, arterial pressure, blood gases, glucose, brain temperature) were monitored. On postoperative day 2, neurologic and histologic outcomes were determined.

Results: Cardiovascular variables before, during, and after CPB were physiologically similar between groups. The desflurane group had better neurologic performance (P = 0.023) and greater postoperative weight gain (P = 0.04) than the fentanyl group. In neocortex, the desflurane group had less tissue damage (P = 0.0015) and fewer dead neurons (P = 0.0015) than the fentanyl group. Hippocampal tissue damage was less in the desflurane group (P = 0.05), but overall, neuronal cell counts in the CA1 sector of the right hippocampus were similar to those in the fentanyl group.     

Desflurane confers neurologic protection for deep hypothermic circulatory arrest in newborn pigs

BACKGROUND: Cardiopulmonary bypass (CPB) and deep hypothermic circulatory arrest (DHCA), as used for infant heart surgery, carry a risk of ischemic neurologic injury. Volatile anesthetics have neuroprotective properties against both global and focal ischemia at normothermia. The authors examined the hemodynamic and neuroprotective effects of desflurane in a piglet CPB-DHCA model. METHODS: Twenty piglets aged 5-10 days received a desflurane- (6-9% expired) or fentanyl-based anesthetic before and during CPB (before and after DHCA). DHCA lasted 90 min at 19 degrees C brain. Cardiovascular variables (heart rate, arterial pressure, blood gases, glucose, brain temperature) were monitored. On postoperative day 2, neurologic and histologic outcomes were determined. RESULTS: Cardiovascular variables before, during, and after CPB were physiologically similar between groups. The desflurane group had better neurologic performance (P = 0.023) and greater postoperative weight gain (P = 0.04) than the fentanyl group. In neocortex, the desflurane group had less tissue damage (P = 0.0015) and fewer dead neurons (P = 0.0015) than the fentanyl group. Hippocampal tissue damage was less in the desflurane group (P = 0.05), but overall, neuronal cell counts in the CA1 sector of the right hippocampus were similar to those in the fentanyl group. CONCLUSIONS: Desflurane-based anesthesia yields hemodynamics during CPB with DHCA that are similar to those with fentanyl-based anesthesia. However, desflurane-based anesthesia improves neurologic and histologic outcomes of CPB-DHCA in comparison with outcomes with fentanyl-based anesthesia.     

Cardiopulmonary bypass induces neurologic and neurocognitive dysfunction in the rat.

BACKGROUND: Neurocognitive dysfunction is a common complication of cardiac surgery using cardiopulmonary bypass (CPB). Elucidating injury mechanisms and developing neuroprotective strategies have been hampered by the lack of a suitable long-term recovery model of CPB. The purpose of this study was to investigate neurologic and neurocognitive outcome after CPB in a recovery model of CPB in the rat. METHODS: Fasted rats (n = 10) were subjected to 60 min of normothermic (37.5 degrees C) nonpulsatile CPB using a roller pump and a membrane oxygenator. Sham-operated controls (n = 10) were not subjected to CPB. Neurologic outcome was assessed on days 1, 3, and 12 after CPB using standardized functional testing. Neurocognitive outcome, defined as the time (or latency) to finding a submerged platform in a Morris water maze (an indicator of visual-spatial learning and memory), was evaluated daily from post-CPB days 3-12. Histologic injury in the hippocampus was also evaluated. RESULTS: Neurologic outcome was worse in the CPB versus the sham-operated controls at all three measurement intervals (P < 0.001). The CPB group also had longer water maze latencies compared with the sham-operated controls (P = 0.004), indicating significant neurocognitive dysfunction after CPB. No difference in histologic injury between groups was observed. CONCLUSIONS: CPB caused both neurologic and neurocognitive impairment in a rodent recovery model. This model could potentially facilitate the investigation of CPB-related injury mechanisms and possible neuroprotective interventions.     

Progesterone is neuroprotective after acute experimental spinal cord trauma in rats.

STUDY DESIGN: A standardized rat contusion model was used to test the hypothesis that progesterone significantly improves neurologic recovery after a spinal cord injury that results in incomplete paraplegia. OBJECTIVES: To compare the effect of progesterone versus a variety of control agents to determine its effectiveness in promoting neurologic recovery after an incomplete rat spinal cord injury. SUMMARY OF BACKGROUND DATA: Progesterone is a neurosteroid, possessing a variety of functions in the central nervous system. Exogenous progesterone has been shown to improve neurologic function after focal cerebral ischemia and facilitates cognitive recovery after cortical contusion in rats. METHODS: A standardized rat contusion model of spinal cord injury using the New York University impactor that resulted in rats with incomplete paraplegia was used. Forty mature male Sprague-Dawley rats were randomly assigned to four groups: laminectomy with sham contusion, laminectomy with contusion without pharmacologic treatment, laminectomy with contusion treated with dimethylsulfoxide and dissolved progesterone, and laminectomy with contusion treated with dimethylsulfoxide. Functional status was assessed weekly using the Basso-Beattie-Bresnehan (BBB) locomotor rating scale for 6 weeks, after which the animals were killed for histologic studies. RESULTS: Rats treated with progesterone had better outcomes (P = 0.0017; P = 0.0172) with a BBB score of 15.5, compared with 10.0 in the dimethylsulfoxide control group and 12.0 in the spinal cord contusion without pharmacologic intervention group. This was corroborated in histologic analysis by relative sparing of white matter tissue at the epicenter of the injury in the progesterone-treated group (P < 0.05). CONCLUSIONS: Rats treated with progesterone had a better clinical and histologic outcome compared with the various control groups. These results indicate potential therapeutic properties of progesterone in the management of acute spinal cord injury.     

The Neuroprotective Effect of Xenon Administration during Transient Middle Cerebral Artery Occlusion in Mice

Background: Xenon has been shown to be neuroprotective in several models of in vitro and in vivo neuronal injury. However, its putative neuroprotective properties have not been evaluated in focal cerebral ischemia. The purpose of this study was to determine if xenon offers neuroprotection in a mouse model of middle cerebral artery occlusion.

Methods: C57BL/6 mice underwent 60 min of middle cerebral artery occlusion. The animals (n = 21 per group) were randomized to receive either 70% xenon + 30% O2, 70% N2O + 30% O2, or 35% xenon + 35% N2O + 30% O2. After 24 h, functional neurologic outcome (on three independent scales: four-point, general, and focal deficit scales) and cerebral infarct size were evaluated.

Results: The 70% xenon + 30% O2 group showed improved functional outcome (median [interquartile range], four-point scale: 2 [2], 70% xenon + 30% O2versus 3 [2], 70% N2O + 30% O2, P = 0.0061; general deficit scale: 9 [6], 70% xenon + 30% O2versus 10 [4], 70% N2O + 30% O2, P = 0.0346). Total cerebral infarct volumes were reduced in the 70% xenon + 30% O2 group compared with the 70% N2O + 30% O2 group (45 +/- 17 mm3versus 59 +/- 11 mm3, respectively; P = 0.0009).     

Desflurane improves neurologic outcome after low-flow cardiopulmonary bypass in newborn pigs

BACKGROUND: Despite improvements in neonatal heart surgery, neurologic complications continue to occur from low-flow cardiopulmonary bypass (LF-CPB) and deep hypothermic circulatory arrest (DHCA). Desflurane confers neuroprotection against ischemia at normothermia and for DHCA. This study compared neurologic outcome of a desflurane-based with a fentanyl-based anesthetic for LF-CPB. METHODS: Thirty piglets aged 1 week received either fentanyl-droperidol (F/D), desflurane 4.5% (Des4.5), or desflurane 9% (Des9) during surgical preparation and CPB. Arterial blood gases, glucose, heart rate, arterial pressure, brain temperature, and cerebral blood flow (laser Doppler flowmetry) were recorded. After CPB cooling (22 degrees C brain) using pH-stat strategy, LF-CPB was performed for 150 min followed by CPB rewarming, separation from CPB, and extubation. On postoperative day 2, functional and histologic outcomes were assessed. RESULTS: Cardiovascular variables were physiologically similar between groups before, during, and after LF-CPB. Cerebral blood flow during LF-CPB (13% of pre-CPB value) did not differ significantly between the groups. Functional disability was worse in F/D than in Des9 (P = 0.04) but not Des4.5 (P = 0.1). In neocortex, histopathologic damage was greater in F/D than in Des4.5 (P = 0.03) and Des9 (P = 0.009). In hippocampus, damage was worse in F/D than in Des9 (P = 0.01) but not Des4.5 (P = 0.08). The incidences of ventricular fibrillation during LF-CPB were 90, 60, and 10% for F/D, Des4.5 (P = 0.06), and Des9 (P = 0.0002), respectively. CONCLUSIONS: Desflurane improved neurologic outcome following LF-CPB compared with F/D in piglets, indicated by less functional disability and less histologic damage, especially with Des9. Desflurane may have produced cardiac protection, suggested by a lower incidence of ventricular fibrillation.     

Modified ultrafiltration may not improve neurologic outcome following deep hypothermic circulatory arrest.

OBJECTIVE: Modified ultrafiltration (MUF) improves systolic blood pressure and left ventricular performance, as well as lowering transfusion requirements, after cardiopulmonary bypass (CPB). MUF has also been shown to enhance acute cerebral metabolic recovery after deep hypothermic circulatory arrest (DHCA), but whether this improves neurologic outcome is unknown. METHODS: Sixteen neonatal piglets underwent CPB and 90 min of DHCA. The hematocrit was maintained between 25 and 30%. Alpha-stat blood gas management was used. After separation from CPB, animals were randomized to 15 min of MUF (n = 8) or no intervention (n = 8). Neurologic injury was assessed with behavior scores and histologic examination. Standardized behavior scores were obtained on post-operative days 1, 3, and 6 (0 = no deficit to 95 = brain death). The percentage of injured neurons by hematoxylin and eosin staining and the degree of reactive astrocytosis by glial filbrillary acidic protein (GFAP) immunohistochemistry were assessed to determine histologic scores in the neocortex and hippocampus (0 = no injury to 4 = diffuse injury). RESULTS: There were no statistically significant differences between groups during CPB. After MUF, the hematocrit was significantly higher (40% +/- 5.7 vs. 28% +/- 3.9, P < 0.001). There were no significant differences in behavior scores between groups (p > 0.1). There was resolution of deficits by day 6 in all animals. Neuronal injury was present in 81% (13/16) of the animals with no statistically significant differences between groups in incidence or severity. CONCLUSIONS: Use of MUF after DHCA does not prevent neuronal injury or improve neurologic outcome in this neonatal swine model.     

Desflurane Improves Neurologic Outcome after Low-flow Cardiopulmonary Bypass in Newborn Pigs

Background: Despite improvements in neonatal heart surgery, neurologic complications continue to occur from low-flow cardiopulmonary bypass (LF-CPB) and deep hypothermic circulatory arrest (DHCA). Desflurane confers neuroprotection against ischemia at normothermia and for DHCA. This study compared neurologic outcome of a desflurane-based with a fentanyl-based anesthetic for LF-CPB.

Methods: Thirty piglets aged 1 week received either fentanyl-droperidol (F/D), desflurane 4.5% (Des4.5), or desflurane 9% (Des9) during surgical preparation and CPB. Arterial blood gases, glucose, heart rate, arterial pressure, brain temperature, and cerebral blood flow (laser Doppler flowmetry) were recorded. After CPB cooling (22[degrees]C brain) using pH-stat strategy, LF-CPB was performed for 150 min followed by CPB rewarming, separation from CPB, and extubation. On postoperative day 2, functional and histologic outcomes were assessed.

Results: Cardiovascular variables were physiologically similar between groups before, during, and after LF-CPB. Cerebral blood flow during LF-CPB (13% of pre-CPB value) did not differ significantly between the groups. Functional disability was worse in F/D than in Des9 (P = 0.04) but not Des4.5 (P = 0.1). In neocortex, histopathologic damage was greater in F/D than in Des4.5 (P = 0.03) and Des9 (P = 0.009). In hippocampus, damage was worse in F/D than in Des9 (P = 0.01) but not Des4.5 (P = 0.08). The incidences of ventricular fibrillation during LF-CPB were 90, 60, and 10% for F/D, Des4.5 (P = 0.06), and Des9 (P = 0.0002), respectively.     

Cerebral Oxygenation during Pediatric Cardiac Surgery Using Deep Hypothermic Circulatory Arrest

Background: Deep hypothermic circulatory arrest is a widely used technique in pediatric cardiac surgery that carries a risk of neurologic injury. Previous work in neonates identified distinct changes in cerebral oxygenation during surgery. This study sought to determine whether the intraoperative changes in cerebral oxygenation vary between neonates, infants, and children and whether the oxygenation changes are associated with postoperative cerebral dysfunction.

Methods: The study included eight neonates, ten infants, and eight children without preexisting neurologic disease. Cerebrovascular hemoglobin oxygen saturation (ScO2), an index of brain oxygenation, was monitored intraoperatively by near-infrared spectroscopy. Body temperature was reduced to 15 degrees Celsius during cardiopulmonary bypass (CPB) before commencing circulatory arrest. Postoperative neurologic status was judged as normal or abnormal (seizures, stroke, coma).

Results: Relative to preoperative levels, the age groups experienced similar changes in ScO2 during surgery: Sco sub 2 increased 30 plus/minus 4% during deep hypothermic CPB, it decreased 62 plus/minus 5% by the end of arrest, and it increased 20 plus/minus 5% during CPB recirculation (all P < 0.001); after rewarming and removal of CPB, ScO2 returned to preoperative levels. During arrest, the half-life of ScO2 was 9 plus/minus 1 min in neonates, 6 plus/minus 1 min in infants, and 4 plus/minus 1 min in children (P < 0.001). Postoperative neurologic status was abnormal in three (12%) patients. The ScO2 increase during deep hypothermic CPB was less in these patients than in the remaining study population (3 plus/minus 2% versus 33 plus/minus 4%, P < 0.00l). There were no other significant ScO2 differences between outcome groups.     

Comparison of the Effects of Propofol and Pentobarbital on Neurologic Outcome and Cerebral Infarct Size after Temporary Focal Ischemia in the Rat

Background: Although propofol is known to have effects on cerebral physiology similar to the barbiturates, a direct comparison of the relative effects of these drugs on outcome from cerebral ischemia has not been performed. The authors postulated that pentobarbital or propofol would yield similar effects on neurologic and histologic outcome from temporary focal ischemia in the rat.

Methods: Wistar rats were anesthetized with sufficient doses of pentobarbital (n = 20) or propofol (n = 20) to cause electroencephalographic burst suppression. The middle cerebral artery was then occluded for 75 min. Animals were awakened 4-6 h after onset of reperfusion and allowed to recover for 1 week. Neurologic function and infarct size were then assessed.

Results: Relevant physiologic values were similar between groups during ischemia and early reperfusion. No difference between groups was observed for severity of hemiparesis (P = 0.10). Total cerebral infarct volumes (median +/- quartile deviation) were similar for the two groups (pentobarbital = 190 +/- 36 mm3; propofol = 200 +/- 24 mm3, P = 0.35).     

Prospective Randomized Trial of Normothermic versus Hypothermic Cardiopulmonary Bypass on Cognitive Function after Coronary Artery Bypass Graft Surgery

Background : Despite significant advances in cardiopulmonary bypass (CPB) technology, surgical techniques, and anesthetic management, central nervous system complications occur in a large percentage of patients undergoing surgery requiring CPB. Many centers are switching to normothermic CPB because of shorter CPB and operating room times and improved myocardial protection. The authors hypothesized that, compared with normothermia, hypothermic CPB would result in superior neurologic and neurocognitive function after coronary artery bypass graft surgery.

Methods : Three hundred patients undergoing elective coronary artery bypass graft surgery were prospectively enrolled and randomly assigned to either normothermic (35.5-36.5[degrees]C) or hypothermic (28-30[degrees]C) CPB. A battery of neurocognitive tests was performed preoperatively and at 6 weeks after surgery. Four distinct cognitive domains were identified and standardized using factor analysis and were then compared on a continuous scale.

Results : Two hundred twenty-seven patients participated in 6-week follow-up testing. There were no differences in neurologic or neurocognitive outcomes between normothermic and hypothermic groups in multivariable models, adjusting for covariable effects of baseline cognitive function, age, and years of education, as well as interaction of these with temperature treatment.     

The neuroprotective effect of xenon administration during transient middle cerebral artery occlusion in mice

BACKGROUND: Xenon has been shown to be neuroprotective in several models of in vitro and in vivo neuronal injury. However, its putative neuroprotective properties have not been evaluated in focal cerebral ischemia. The purpose of this study was to determine if xenon offers neuroprotection in a mouse model of middle cerebral artery occlusion. METHODS: C57BL/6 mice underwent 60 min of middle cerebral artery occlusion. The animals (n = 21 per group) were randomized to receive either 70% xenon + 30% O2, 70% N2O + 30% O2, or 35% xenon + 35% N2O + 30% O2. After 24 h, functional neurologic outcome (on three independent scales: four-point, general, and focal deficit scales) and cerebral infarct size were evaluated. RESULTS: The 70% xenon + 30% O2 group showed improved functional outcome (median [interquartile range], four-point scale: 2 [2], 70% xenon + 30% O2 versus 3 [2], 70% N2O + 30% O2, P = 0.0061; general deficit scale: 9 [6], 70% xenon + 30% O2 versus 10 [4], 70% N2O + 30% O2, P = 0.0346). Total cerebral infarct volumes were reduced in the 70% xenon + 30% O2 group compared with the 70% N2O + 30% O2 group (45 +/- 17 mm3 versus 59 +/- 11 mm3, respectively; P = 0.0009). CONCLUSIONS: In this model of transient focal cerebral ischemia, xenon administration improved both functional and histologic outcome.     

川芎嗪对大鼠脊髓损伤后神经功能恢复作用的研究

目的探讨川芎嗪(TMP)对大鼠脊髓损伤后后肢运动功能恢复的影响。方法雄性成年SD大鼠24只,随机均分为假手术组、对照组及TMP治疗组。采用改良Allen法建立大鼠胸段脊髓打击模型,HE染色观察伤后4周伤段脊髓残存组织的面积,采用斜板试验和运动功能评分观察大鼠后肢运动功能的恢复情况。结果大鼠脊髓损伤后1～4周,TMP治疗组后肢运动功能评分明显高于对照组,两组间差异有显著性(P<0.05)。伤后4周,TMP组伤段残存脊髓组织的面积大于对照组(P<0.01)。结论TMP能明显减少脊髓损伤后伤区的坏死和萎缩,并促进大鼠后肢运动功能的恢复。     

Neurological outcomes in coronary surgery: independent effect of avoiding cardiopulmonary bypass

BACKGROUND: Recent studies examining neuroprotective effects of off-pump coronary artery bypass grafting (CABG) have shown inconsistent results. We examined our database to quantify the independent effects of avoidance of cardiopulmonary bypass (CPB) and aortic manipulation on neurologic outcomes after CABG. METHODS: A total of 2,327 consecutive cases undergoing isolated CABG between April 1997 and May 2001 were identified at our two institutions. Patients were divided into three groups: on CPB, off-pump with aortic manipulation, and off-pump without aortic manipulation. To control for the confounding effects of other risk factors, we performed a multivariate logistic regression analysis. Potential covariates considered in the logistic model included age, sex, redo operations, diabetes, chronic obstructive pulmonary disease, neurologic disease, peripheral vascular disease, ejection fraction, and priority of operation. RESULTS: A total of 1,210 cases were performed on CPB, compared with 520 off-pump with aortic manipulation, and 597 off-pump without aortic manipulation. The incidence of focal neurologic deficit was 1.6% (n = 19) in the on-pump group, 0.4% (n = 2) in the off-pump with aortic manipulation group, and 0.5% (n = 3) for the off-pump without aortic manipulation group (p for trend = 0.027). The results of the multivariate logistic regression analysis demonstrated that use of CPB was a risk factor for focal neurologic deficit, with an odds ratio of 3.82 (95% confidence interval, 1.41 to 10.34; p = 0.005). Aortic manipulation did not significantly influence neurologic outcome in off-pump patients. CONCLUSIONS: Off-pump operation, with or without aortic manipulation, reduces adverse neurologic outcomes compared with on-pump procedures.