Anterior fontanel pressure and visual evoked potentials in neonates and infants undergoing profound hypothermic circulatory arrest

To determine the effects of cardiopulmonary bypass with profound hypothermic circulatory arrest (PHCA) on anterior fontanel pressure (AFP) and visual evoked potentials (VEPs), 21 neonates and infants undergoing cardiopulmonary bypass (CPB) with PHCA for surgical correction of congenital heart defects were studied. Mean (+/- SD) minimum nasopharyngeal, esophageal, and rectal temperatures of 16.4 +/- 2.2, 11.2 +/- 2.7, and 17.7 +/- 1.9 degrees C, respectively, were achieved for a mean duration of PHCA of 51.6 +/- 18.7 min. AFP increased significantly above pre-CPB values for the first 21.7 +/- 8.1 min of rewarming. The duration of this increase in AFP was related logarithmically and directly to the product of the nasopharyngeal temperature (NPT) at the end of PHCA and the duration of PHCA (r2 = 0.82, P less than 0.0001). Nineteen of these patients had simultaneous monitoring of VEPs. The latency of both the N70 and P100 components of the VEPs increased as temperature decreased. The cerebral perfusion pressure was linearly and inversely related to the AFP (r2 = 0.72, P less than 0.01). The VEPs disappeared as a nasopharyngeal temperature (NPT) of 18.9 +/- 2.8 degrees C and reappeared after 21.9 +/- 8.8 min post-PHCA at an NPT of 32.8 +/- 1.4 degrees C. There was no significant difference between duration of increased AFP (20.9 +/- 8.1 min) and the duration of absence of VEPs during the post-PHCA period. The duration of increased AFP correlated linearly and directly with the duration of absence of VEPs (r2 = 0.84, P less than 0.005). These data demonstrate that transient neurophysiologic dysfunction occurs after PHCA. This dysfunction is related to the duration of elevation of the AFP and cannot be explained solely by a temperature effect.     

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.     

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.     

Reduced jugular venous oxygen saturation during rewarming from deep hypothermic circulatory arrest: cerebral overextraction?

Deep hypothermic circulatory arrest may impair cerebral cellular functions, and physiological parameters following circulatory arrest may deviate from the normal. The intention of this study was to monitor jugular venous oxygen saturation during cardiopulmonary bypass before and after deep hypothermic circulatory arrest. Jugular venous oxygen saturation were obtained on 18 patients by using a retrograde jugular vein catheter during replacement of the ascending aorta. Indications for operations were ascending aortic dilatation (n=15) and acute aortic dissection (n=3). Hypothermic cardiopulmonary bypass (233+/-60 min), cardioplegic arrest (105+/-37 min) and circulatory arrest (22+/-7 min) were utilized during the operations. Jugular venous oxygen saturation increased during hypothermia and decreased during rewarming. Compared with cooling, jugular venous oxygen saturation during the initial part of rewarming were significantly lower (87+/-5% vs. 97+/-1%, 89+/-4% vs. 95+/-2%, 81+/-4% vs. 87+/-5% at 16, 20 and 24 degrees C respectively, p<0.05). One patient required re-exploration because of bleeding. All patients were found neurologically normal before being discharged from the hospital (mean 14+/-7 days). In conclusion, jugular venous oxygen saturation is inversely related to the body temperature in patients undergoing hypothermic cardiopulmonary bypass. Significantly decreased jugular venous oxygen saturation during the initial part of rewarming may signify an increased cerebral extraction of oxygen.     

Cerebral perfusion during canine hypothermic cardiopulmonary bypass: effect of arterial carbon dioxide tension

Cerebral blood flow (radioactive microspheres), intracranial pressure (subdural bolt), and retinal histopathology were examined in 20 dogs undergoing 150 minutes of hypothermic (28 degrees C) cardiopulmonary bypass to compare alpha-stat (arterial carbon dioxide tension, 40 +/- 1 mm Hg; n = 10) and pH-stat (arterial carbon dioxide tension, 61 +/- 1 mm Hg; n = 10) techniques of arterial carbon dioxide tension management. Pump flow (80 mL.kg-1.min-1), mean aortic pressure (78 +/- 2 mm Hg), and hemoglobin level (87 +/- 3 g/L [8.7 +/- 0.3 g/dL]) were maintained constant. During bypass, intracranial pressure progressively increased in the alpha-stat group from 6.0 +/- 1.0 to 13.9 +/- 1.8 mm Hg (p less than 0.05) and in the pH-stat group from 7.7 +/- 1.1 to 14.7 +/- 1.4 mm Hg (p less than 0.05), although there was no evidence of loss of intracranial compliance or intracranial edema formation as assessed by brain water content. With cooling, cerebral blood flow decreased by 56% to 62% in the alpha-stat group (p less than 0.05) and by 48% to 56% in the pH-stat group (p less than 0.05). However, 30 minutes after rewarming to 37 degrees C, cerebral blood flow in both groups failed to increase and remained significantly depressed compared with baseline values. Both groups showed similar amounts of ischemic retinal damage, with degeneration of bipolar cells found in the inner nuclear layer in 67% of animals. We conclude that, independent of the arterial carbon dioxide tension management technique, (1) cerebral perfusion decreased comparably during prolonged hypothermic bypass, (2) intracranial pressure increases progressively, (3) ischemic damage to retinal cells occurs despite maintenance of aortic pressure and flow, and (4) a significant reduction in cerebral perfusion persists after rewarming.     

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.     

Changes in cerebral and somatic oxygenation during stage 1 palliation of hypoplastic left heart syndrome using continuous regional cerebral perfusion

OBJECTIVES: Stage 1 palliation of hypoplastic left heart syndrome requires the interruption of whole-body perfusion. Delayed reflow in the cerebral circulation secondary to prolonged elevation in vascular resistance occurs in neonates after deep hypothermic circulatory arrest. We examined relative changes in cerebral and somatic oxygenation with near-infrared spectroscopy while using a modified perfusion strategy that allowed continuous cerebral perfusion. METHODS: Nine neonates undergoing stage 1 palliation for hypoplastic left heart syndrome had regional tissue oxygenation continuously measured by frontal cerebral and thoraco-lumbar (T10-L2) somatic (renal) reflectance oximetry probes (rSO(2), INVOS; Somanetics, Troy, Mich). Surgery was accomplished using cardiopulmonary bypass with whole-body cooling (18 degrees C-20 degrees C) and regional cerebral perfusion through the innominate artery at flow rates guided by estimated minimum flow requirements and measured rSO(2) during reconstruction of the aortic arch. Data were logged at 1-minute intervals and analyzed using repeated measures analysis of variance. RESULTS: A total of 3176 minutes of data were analyzed. Prebypass cerebral rSO(2) was 65.4 +/- 8.9, and somatic rSO(2) was 58.9 +/- 12.4 (P <.001, cerebral vs somatic). During regional cerebral perfusion, cerebral rSO(2) was 80.7 +/- 8.6, and somatic rSO(2) was 41.4 +/- 7.1 (P <.001). Postbypass cerebral rSO(2) was 53.2 +/- 14.9, and somatic rSO(2) was 76.4 +/- 7.7 (P <.001). The risk of cerebral desaturation was significantly increased after cardiopulmonary bypass. CONCLUSIONS: Cerebral oxygenation was maintained during regional cerebral perfusion at prebypass levels with deep hypothermia. However, after rewarming and separation from cardiopulmonary bypass, cerebral oxygenation was lower compared with prebypass or somatic values. These results indicate that cerebrovascular resistance is increased after deep hypothermic cardiopulmonary bypass, even with continuous perfusion techniques, placing the cerebral circulation at risk postoperatively.     

Pharmacologic cerebral capillary blood flow improvement after deep hypothermic circulatory arrest: an intravital fluorescence microscopy study in pigs

BACKGROUND: Despite meticulous investigation of bypass techniques for deep hypothermic circulatory arrest, unfavorable long-term neurologic deficits have been well documented. Our aim was to improve brain perfusion by reducing platelet plugging with a glycoprotein IIb/IIIa inhibitor (eptifibatide) in an experimental model of deep hypothermic circulatory arrest-reperfusion in pigs. METHODS: Two groups of 12 piglets each (eptifibatide group [eptifibatide + unfractionated heparin] vs UFH group [only unfractionated heparin]) underwent 10 minutes of normothermic bypass, 40 minutes of cooling during cardiopulmonary bypass (hematocrit, 30%; cardiopulmonary bypass flow, 100 mL x kg(-1) x min(-1)), 60 minutes of circulatory arrest at 15 degrees C, and a 40-minute rewarming period. Intravital fluorescence microscopy of pial vessels at set intervals was performed. RESULTS: During the cooling period, there was a tendency toward reduced functional capillary density values without statistical significance in both groups. During reperfusion, the eptifibatide group demonstrated a significantly decreased platelet adhesion and aggregation (at 30 minutes of reperfusion: functional capillary density, 104% +/- 3% vs 77% +/- 4% relative to baseline, P = .02; red blood cell velocity, 0.65 vs 0.30 mm/s, P < .004). A more rapid recovery of tissue oxygenation (P < .001) was documented. Furthermore, a significant microvascular permeability reduction was achieved compared with that seen in the UFH group (P < .02). The use of eptifibatide resulted in fewer ultrastructural changes in hippocampal tissue, which is demonstrated by histologic examination. CONCLUSIONS: Platelet plugging reduction with the glycoprotein IIb/IIIa inhibitor eptifibatide improves cerebral capillary blood flow and reduces cerebral ischemia in the setting of deep hypothermic circulatory arrest. Furthermore, significant endothelial cell injury and perivascular edema reduction can be achieved.     

Blood flow distribution in infant pigs subjected to surface cooling, deep hypothermia, and circulatory arrest. Deleterious effects in pigs with left-to-right shunts

Surface cooling, deep hypothermia and circulatory arrest have been used effectively for correction of congenital heart defects in infancy. Which patients are best suited for this technique has not been addressed. The addition of surface cooling to deep hypothermia and circulatory arrest provides homogeneous cooling and avoids swelling due to reperfusion injury after circulatory arrest. However, surface cooling in patients with large left-to-right shunts causes increased peripheral resistance and increased shunting which can result in decreased perfusion of vital organs. The purpose of this study is to measure the effect of a large left-to-right shunt on total organ blood flow distribution in infant piglets during surface cooling, deep hypothermia, and circulatory arrest. Eleven 2-week-old piglets had surface cooling, deep hypothermia, and circulatory arrest for 45 minutes, followed by rewarming and weaning from cardiopulmonary bypass. Microspheres (15 mu) were injected before surface cooling, at 28 degrees C, at 15 degrees C, and after weaning from cardiopulmonary bypass. Group I (five piglets) was the control. Group II (six piglets) had a large (6 mm) left-to-right aortopulmonary shunt established before microsphere injection. Cardiac outputs in both Groups I and II decreased with surface cooling. The distribution of cardiac output in Group I did not change with surface cooling; however, Group II pigs showed marked change in distribution of cardiac output, resulting in decreased renal, visceral, and pulmonary flow (p less than 0.05). Amylase determinations before and after surface cooling, deep hypothermia, and circulatory arrest were unchanged in Group I but elevated in Group II (p less than 0.05). These observations suggest altered cellular metabolism in visceral organs during the period of surface cooling which may be compounded by circulatory arrest and rewarming.     

Auditory brainstem evoked responses and temperature monitoring during pediatric cardiopulmonary bypass

PURPOSE: To examine the effects of temperature on auditory brainstem responses (ABRs) in infants during hypothermic cardiopulmonary bypass for total circulatory arrest (TCA). The relationship between ABRs (as a surrogate measure of core-brain temperature) and body temperature as measured at several temperature monitoring sites was determined. METHODS: In a prospective, observational study, ABRs were recorded non-invasively at normothermia and at every 1 or 2 degrees C change in ear-canal temperature during cooling and rewarming in 15 infants (ages: 2 days to 14 months) that required TCA. The ABR latencies and amplitudes and the lowest temperatures at which an ABR was identified (the threshold) were measured during both cooling and rewarming. Temperatures from four standard temperature monitoring sites were simultaneously recorded. RESULTS: The latencies of ABRs increased and amplitudes decreased with cooling (P < 0.01), but rewarming reversed these effects. The ABR threshold temperature as related to each monitoring site (ear-canal, nasopharynx, esophagus and bladder) was respectively determined as 23 +/- 2.2 degrees C, 20.8 +/- 1.7 degrees C, 14.6 +/- 3.4 degrees C, and 21.5 +/- 3.8 degrees C during cooling and 21.8 +/- 1.6 degrees C, 22.4 +/- 2.0 degrees C, 27.6 +/- 3.6 degrees C, and 23.0 +/- 2.4 degrees C during rewarming. The rewarming latencies were shorter and Q10 latencies smaller than the corresponding cooling values (P < 0.01). Esophageal and bladder sites were more susceptible to temperature variations as compared with the ear-canal and nasopharynx. CONCLUSION: No temperature site reliably predicted an electrophysiological threshold. A faster latency recovery during rewarming suggests that body temperature monitoring underestimates the effects of rewarming in the core-brain. ABRs may be helpful to monitor the effects of cooling and rewarming on the core-brain during pediatric cardiopulmonary bypass.     

Cold retrograde cerebral perfusion improves cerebral protection during moderate hypothermic circulatory arrest: A long-term study in a porcine model.

BACKGROUND: Deep hypothermic circulatory arrest is an effective method of cerebral protection, but it is associated with long cardiopulmonary bypass times and coagulation disturbances. Previous studies have shown that retrograde cerebral perfusion can improve neurologic outcomes after prolonged hypothermic circulatory arrest. We tested the hypothesis that deep hypothermic retrograde cerebral perfusion could improve cerebral outcome during moderate hypothermic circulatory arrest. METHODS: Twelve pigs (23-29 kg) were randomly assigned to undergo either retrograde cerebral perfusion (15 degrees C) at 25 degrees C or hypothermic circulatory arrest with the head packed in ice at 25 degrees C for 45 minutes. Flow was adjusted to maintain superior vena cava pressure at 20 mm Hg throughout retrograde cerebral perfusion. Hemodynamic, electrophysiologic, metabolic, and temperature monitoring were carried out until 4 hours after the start of rewarming. Daily behavioral assessment was performed until elective death on day 7. A postmortem histologic analysis of the brain was carried out on all animals. RESULTS: In the retrograde cerebral perfusion group, 5 (83%) of 6 animals survived 7 days compared with 2 (33%) of 6 in the hypothermic circulatory arrest group. Complete behavioral recovery was seen in 4 (67%) animals after retrograde cerebral perfusion but only in 1 (17%) animal after hypothermic circulatory arrest. Postoperative levels of serum lactate were higher, and blood pH was lower in the hypothermic circulatory arrest group. There were no significant hemodynamic differences between the study groups. CONCLUSIONS: Cold hypothermic retrograde cerebral perfusion during moderate hypothermic circulatory arrest seems to improve neurologic outcome compared with moderate hypothermic circulatory arrest with the head packed in ice.     

Brain oxygenation and metabolism during selective cerebral perfusion in neonates.

OBJECTIVE: To investigate the possible neuroprotective effects of selective cerebral perfusion (SCP) during deep hypothermic circulatory arrest on brain oxygenation and metabolism in newborn piglets. METHODS: Newborn piglets 2-4 days of age, anesthetized and mechanically ventilated, were used for the study. The animals were placed on cardiopulmonary bypass, cooled to 18 degrees C and put on SCP (20 ml/(kg min)) for 90 min. After rewarming, the animals were monitored through 2h of recovery. Oxygen pressure in the microvasculature of the cortex was measured by oxygen-dependent quenching of phosphorescence. The extracellular level of dopamine in striatum was measured by microdialysis and hydroxyl radicals by ortho-tyrosine levels. Levels of phosphorylated cAMP response element binding protein (pCREB) in striatal tissue were measured by Western blots using antibodies specific for phosphorylated CREB. The results are presented as mean+/-SD (p<0.05 was significant). RESULTS: Pre-bypass cortical oxygen pressure was 48.9+/-11.3 mmHg and during the first 5 min of SCP, the peak of the histogram, corrected to 18 degrees C, decreased to 11.2+/-3.8 mmHg (p<0.001) and stayed near that value to the end of bypass. The mean value for the peak of the histograms measured at the end of SCP was 8+/-3 mmHg (p<0.001). SCP completely prevented the deep hypothermic circulatory arrest-dependent increase in extracellular dopamine and hydroxyl radicals. After SCP, there was a statistically significant increase in pCREB immunoreactivity (534+/-60%) compared to the sham-operated group (100+/-63%, p<0.005). Measurements of total CREB showed that SCP did induce a statistically significant increase in CREB as compared to sham-operated animals (168+/-31%, p<0.05). CONCLUSION: SCP, as compared to DHCA, improved cortical oxygenation and prevented increases in the extracellular dopamine and hydroxyl radicals. The increase in pCREB in the striatum following SCP may contribute to improved cellular recovery after this procedure.     

Hemodilution elevates cerebral blood flow and oxygen metabolism during cardiopulmonary bypass in piglets

BACKGROUND: Hemodilution continues to be widely used during cardiopulmonary bypass (CPB) for both adults and children. Previous studies with nonbypass models have suggested that an increase in cerebral blood flow (CBF) compensates for the reduced oxygen-carrying capacity; however, this increased CBF is achieved by an increase in cardiac output. We hypothesized that even with the fixed-flow perfusion of CPB, CBF would be increased during hemodilution. METHODS: Two experiments were conducted and analyzed separately. In each experiment, 10 piglets were randomized to two different groups, one with a total blood prime yielding a high hematocrit (25% or 30%), and the other with a crystalloid prime resulting in a low hematocrit (10% or 15%). Animals were cooled with pH-stat strategy at full flow (100 or 150 mL.kg(-1).min(-1)) to a nasopharyngeal temperature of 15 degrees C, a period of low flow (50 mL.kg(-1).min(-1)) preceding deep hypothermic circulatory arrest (45 or 60 minutes), and a period of rewarming at full flow. Cerebral blood flow was measured at the beginning of CPB, at the end of cooling, at the end of low flow, 5 minutes after the start of rewarming, and at the end of rewarming by injection of radioactive microspheres. RESULTS: Mean arterial pressure was significantly greater with higher hematocrit at each time point (p< 0.05). Cerebral blood flow and the cerebral metabolic rate of oxygen decreased during cooling and further during low flow bypass but were significantly greater with lower hematocrit during mild hypothermia and at the end of rewarming (p< 0.05). CONCLUSIONS: Hemodilution is associated with decreased perfusion pressure, increased CBF and increased the cerebral metabolic rate of oxygen during hypothermic CPB.     

The effects of pulsatile pumping on tissue perfusion and renal function during deep hypothermic low flow perfusion

The effects of pulsatile pumping on tissue perfusion and renal function during deep hypothermic low flow perfusion were compared with non-pulsatile pumping. Twelve dogs were classified into 2 groups by the perfusion technique used. Animals were core cooled to 20 degrees C esophageal temperature with 80 ml/kg/min perfusion rate and maintained at the level for 2 hours with low flow perfusion (LFP) (30 ml/kg/min), then rewarmed to 35 degrees C with 80 ml/kg/min flow rate. As compared with the non-pulsatile group, pulsatile group demonstrated greater urine output during rewarming (p less than 0.05) and greater lymph flow during core cooling (p less than 0.05). The non-pulsatile group showed higher lymph/plasma protein concentration ratio (Lc/Pc) during LFP and rewarming (p less than 0.05), and greater plasma protein clearance during rewarming (p less than 0.05), and much higher increase of interstitial fluid pressure. The lesser water retention during bypass was also noted in the pulsatile group (28.6 +/- 27.6 ml/kg vs 85.4 +/- 52.1 ml/kg, p less than 0.05). These findings have suggested that the pulsatile perfusion may be useful for the infant cardiopulmonary bypass reducing tissue edema and preserving better renal function.     

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.     

Differences between aortic and radial artery pressure associated with cardiopulmonary bypass.

Previous investigators have identified an aortic-to-radial artery pressure gradient thought to develop during rewarming and discontinuation of cardiopulmonary bypass. The authors measured mean aortic and radial artery pressures before, during, and after cardiopulmonary bypass in 30 patients, to determine when the pressure gradient develops. The pressure gradient was also measured before and after intravenous injections of sodium nitroprusside (1 microgram/kg) and phenylephrine (7 micrograms/kg) to determine the effect of changes in systemic vascular resistance. A significant (P less than 0.05) pressure gradient (mean +/- SEM = 4.9 +/- 0.7 mmHg) developed upon initiation of cardiopulmonary bypass. This gradient did not change significantly during the middle of bypass (4.2 +/- 0.5 mmHg), with rewarming (4.8 +/- 0.7 mmHg), immediately prior to discontinuation of bypass (4.6 +/- 0.7), or 5 and 10 min following bypass (4.9 +/- 0.9 and 4.8 +/- 0.7 mmHg). Sodium nitroprusside significantly decreased systemic vascular resistance, by 15 +/- 2%, during the middle of bypass but did not affect the pressure gradient. Likewise, phenylephrine increased the systemic vascular resistance by 52 +/- 6% and 34 +/- 4% during the middle of bypass and rewarming, respectively, without affecting the pressure gradient. Although the exact mechanisms responsible for the pressure gradient remain unknown, these results suggest its etiology is associated with events occurring during initiation of cardiopulmonary bypass rather than with rewarming or discontinuation of cardiopulmonary bypass.     

Optimal pH strategy for selective cerebral perfusion.

OBJECTIVE: Selective cerebral perfusion (SCP) affords brain protection superior to hypothermic circulatory arrest (HCA) for prolonged aortic arch procedures. Optimal pH strategy for HCA is controversial; for SCP it is unknown. We compared pH strategies during SCP in a survival pig model. METHODS: Twenty juvenile pigs (26+/-2.4 kg), randomized to alpha-stat (n=10) or pH-stat (n=10) management, underwent cooling to 20 degrees C on cardiopulmonary bypass (CPB) followed by 90 min of SCP at 20 degrees C. SCP was conducted with a mean pressure of 50 mmHg and hematocrit of 22.5%. Using fluorescent microspheres and sagittal sinus blood sampling, cerebral blood flow (CBF) and oxygen metabolism (CMRO2) were assessed at the following time points: baseline, after 30 min cooling (20 degrees C), 30 min of SCP, 90 min of SCP, 15 min post-CPB and 2h post-CPB. Visual evoked potentials (VEP) were assessed at baseline and monitored for 2h during recovery. Neurobehavioral recovery (10=normal) was assessed in a blinded fashion for 7 postoperative days. RESULTS: There were no significant differences between the groups at baseline. CBF was significantly higher at the end of cooling, and after 30 and 90 min of SCP in the pH-stat group (P=0.02, 0.007, 0.03). CMRO2 was also higher with pH-stat (P=0.06, 0.04, 0.10). Both groups showed prompt return to values close to baseline after rewarming (P=ns). VEP suggested a trend towards improved recovery in the alpha-stat group at 2h post-CPB, P=0.15. However, there were no significant differences in neurobehavioral score: (alpha-stat versus pH-stat) median values 7 and 7.5 on day 1; 9 and 9 on day 4, and 10 and 10 on day 7. CONCLUSIONS: These data suggest that alpha-stat management for SCP provides more effective metabolic suppression than pH-stat, with lower CBF. Clinically, the better preservation of cerebral autoregulation during alpha-stat perfusion should reduce the risk of embolization.     

Direct visualization of minimal cerebral capillary flow during retrograde cerebral perfusion: an intravital fluorescence microscopy study in pigs

BACKGROUND: Retrograde cerebral perfusion (RCP) is used in some centers during aortic arch surgery for brain protection during hypothermic circulatory arrest. It is still unclear however whether RCP provides adequate microcirculatory blood flow at a capillary level. We used intravital microscopy to directly visualize the cerebral capillary blood flow in a piglet model of RCP. METHODS: Twelve pigs (weight 9.7 +/- 0.9 kg) were divided into two groups (n = 6 each): deep hypothermic circulatory arrest (DHCA) and RCP. After the creation of a window over the parietal cerebral cortex, pigs underwent 10 minutes of normothermic bypass and 40 minutes of cooling to 15 degrees C on cardiopulmonary bypass ([CPB] pH-stat, hemocrit 30%, pump flow 100 mL x kg(-1) x min(-1)). This was followed by 45 minutes of DHCA and rewarming on CPB to 37 degrees C. In the RCP group the brain was retrogradely perfused (pump flow 30 mL x kg(-1) x min(-1)) during DHCA through the superior vena cava after inferior vena cava occlusion. Plasma was labeled with fluorescein-isothiocyanate-dextran for assessing microvascular diameter and functional capillary density (FCD), defined as total length of erythrocyte-perfused capillaries per observation area. Cerebral tissue oxygenation was determined by nicotinamide adenine dinucleotide hydrogen (NADH) autofluorescence, which increases during tissue ischemia. RESULTS: During normothermic and hypothermic antegrade cerebral perfusion the FCD did not significantly change from base line (97% +/- 14% and 96% +/- 12%, respectively). During retrograde cerebral perfusion the FCD decreased highly significantly to 2% +/- 2% of base line values (p < 0.001). Thus there was no evidence of significant capillary blood flow during retrograde cerebral perfusion. The microvascular diameter of cerebral arterioles that were slowly perfused significantly decreased to 27% +/- 6% of base line levels during RCP. NADH fluorescence progressively and significantly increased during RCP, indicating poorer tissue oxygenation. At the end of retrograde cerebral perfusion there was macroscopic evidence of significant brain edema. CONCLUSIONS: RCP does not provide adequate cerebral capillary blood flow and does not prevent cerebral ischemia. Prolonged RCP induces brain edema. However, there might be a role for a short period of RCP to remove air and debris from the cerebral circulation after DHCA because retrograde flow could be detected in cerebral arterioles.     

Is Maintenance of Cerebral Hypothermia the Principal Mechanism by which Retrograde Cerebral Perfusion Provides Better Brain Protection than Hypothermic Circulatory Arrest?

OBJECTIVE: Retrograde cerebral perfusion (RCP) provides better brain protection than hypothermic circulatory arrest (HCA) alone. The mechanism by which RCP improves brain protection during circulatory arrest remains unknown. The purpose of the study in pigs was to determine if RCP improves brain protection mainly as a result of its ability to maintain cerebral hypothermia. METHODS: Fifteen pigs were subjected to 120 minutes of HCA alone (HCA group, n = 5), HCA + RCP at perfusion pressures of 23 to 29 mmHg (RCP-low group, n = 5), or at perfusion pressures of 34-40 mmHg (RCP-high group, n = 5) at 15 degrees C, followed by 60 minutes of normothermic cardiopulmonary bypass (CPB). After brain temperature reached 15 degrees C, HCA was initiated with or without RCP. Temperatures in the brain, esophagus, and perfusate/blood were monitored continuously. Brain tissue blood flow was measured continuously using a laser flowmeter. Brain oxygen extraction was calculated from the oxygen contents in arterial and venous blood samples. RESULTS: During cooling and rewarming, the change in temperature was slower in the brain than in the esophagus. A similar degree of spontaneous rewarming (from 15 degrees C to 17/18 degrees C) occurred in the brain during HCA and RCP. This indicates that RCP does not provide better maintenance of cerebral hypothermia during circulatory arrest than HCA alone. The esophageal temperature rose more slowly during RCP than during HCA alone, indicating that RCP maintains better hypothermia in the body. During RCP, the brain extracted oxygen continuously from the blood, indicating that RCP may provide nutrient flow to the brain. CONCLUSION: In an acute pig model, maintenance of cerebral hypothermia does not appear to be the principal mechanism by which RCP provides better brain protection than HCA alone. Retrograde cerebral perfusion provides nutrient flow/oxygen to brain tissue, leading to better brain protection than HCA alone.     

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.