Period Of Hypothermic Circulatory Arrest Research Articles

A Case of Severe Diffuse Venous Thromboembolism Associated with Aprotinin and Hypothermic Circulatory Arrest in a Cardiac Surgical Patient with Factor V Leiden

A Case of Severe Diffuse Venous Thromboembolism Associated with Aprotinin and Hypothermic Circulatory Arrest in a Cardiac Surgical Patient with Factor V Leiden

Hypertonic Saline Dextran Improves Outcome After Hypothermic Circulatory Arrest: A Study in a Surviving Porcine Model

Hypertonic saline dextran (HSD) has been shown to have neuroprotective properties. In the present study we have assessed its potential neuroprotective efficacy in the setting of hypothermic circulatory arrest in a surviving porcine model. Twenty-four pigs were randomized to receive two 5-minute intravenous infusions (4 mL/kg) of either HSD (7.5 % saline, 6% dextran 70) or normal saline immediately after and 4 hours after a 75-minute period of hypothermic circulatory arrest at a brain temperature of 18 degrees C. The 7-day survival was 75% in the HSD group and 66% in the control group (p > 0.9). Brain total histopathologic score was lower in the HSD group (p = 0.01). Postoperative behavioral scores were higher in the HSD group on the second day after surgery (p = 0.03). Intracranial pressure was lower in the HSD group from 45 minutes to 8 hours after hypothermic circulatory arrest (p = 0.03). Cerebral perfusion pressure was higher in the HSD group from 45 minutes to 3 hours after hypothermic circulatory arrest (p = 0.06). Brain lactate concentration was lower in the HSD group when compared with controls (p = 0.05). Furthermore, brain glucose levels tended to be higher and brain lactate-pyruvate ratio and lactate-glucose ratio were lower in the HSD group. Brain tissue oxygen partial pressures were somewhat higher in the HSD group (p = 0.08). The use of HSD in experimental hypothermic circulatory arrest is associated with significantly better neurologic recovery, better histopathology, lower intracranial pressure, higher cerebral perfusion pressure, and better preservation of brain metabolism.

Long-Term Results After Primary One-Stage Repair of Transposition of the Great Arteries and Aortic Arch Obstruction

The study was designed to evaluate perioperative and late results after primary, single-stage arterial switch operation (ASO) associated with aortic arch obstruction repair. Outcome of patients with more than five years of follow-up were analyzed. The treatment of patients with transposition of the great arteries, or other forms of ventriculoarterial discordance suitable for an ASO, with coexisting arch obstruction is a difficult task. Single-stage repair has become the treatment of choice at many institutions, but large series with long-term results are seldom reported. Between 1990 and 1998, a primary operation including aortic arch repair through a midline sternotomy was performed in 38 patients. The relief of arch obstruction was accomplished during a period of hypothermic circulatory arrest, employing a wide pericardial patch to enlarge the inner curvature of the entire arch in most patients. There were nine (24%) hospital deaths. None could be directly related to aortic arch repair, but additional risk factors for an ASO were common (right ventricular hypoplasia, complex coronary anatomy, uncommon relationship between the great vessels or severe pulmonary hypertension). There were no late deaths. Four patients required cardiac reoperation, whereas three underwent successful treatment of recurrent coarctation with balloon angioplasty. Infants with ventriculoarterial discordance and aortic arch obstruction represent a high-risk subgroup of candidates for an ASO. Despite a non-negligible operative mortality, single-stage primary repair represents the treatment of choice, and follow-up of operative survivors is favorable. Pericardial patch enlargement is a reliable technique for arch obstruction repair.

Brain, spine, and muscle cytochrome Cu-A redox patterns of change during hypothermic circulatory arrest in swine

Past near infrared spectroscopy (NIRS) studies have reported different changes in cytochrome C oxidase (Cyt) redox status during similar interventions that cause tissue ischaemia. We investigated whether there were distinctive differences when NIRS signals were obtained simultaneously from different tissues during total circulatory arrest. Forty-two healthy 10 kg commercial swine ( Sus scrofa) on cardiopulmonary bypass, each underwent 2 to 8 sequential periods of hypothermic circulatory arrest for 7.5 min. Prior to each arrest, key physiologic variables were adjusted to 1 of 81 combinations of high, normal, or low levels of core temperature, hematocrit, pH, and serum glucose. Each combination was repeated at least twice. Simultaneous NIRS monitoring yielded 202 brain, 191 spine, and 199 muscle Cyt data sets, which were then classified into 13 distinctive patterns of change. The data sets always differed between tissues in the same arrest trial and subject. Typically, brain Cyt rapidly became more reduced at the start of arrest and changed little thereafter, muscle Cyt behaved comparably to brain Cyt but continued to become reduced throughout the arrest, and spine Cyt either did not change status or gradually became more reduced over the course of arrest. The spine pattern's mean rate of change was 12 times slower than those of the brain or muscle. The Cyt patterns of change were classified into 13 groups which were significantly related to core temperature in the brain and spine, and hematocrit in muscle. The respiratory response in mitochondria during systemic circulatory arrest differs between brain, spine and muscle tissues in the same subject.

Aortic Arch Replacement Using a Trifurcated Graft: Simple, Versatile, and Safe

Hypothermic selective antegrade cerebral perfusion during aortic arch replacement may prevent adverse neurologic sequelae. It can be provided via balloon-tipped catheters or a branched graft sewn to the brachiocephalic vessels. We report a consecutive series of total arch replacement using a trifurcated graft. From September 1999 through October 2004, 109 patients underwent nonemergent total arch replacement using this technique. The graft, placed during a period of hypothermic circulatory arrest, was used for selective cerebral perfusion during the arch reconstruction. Adverse outcomes were seen in 9 (8.3%) patients: hospital death in 5 (4.6%), and stroke in 5 (4.6%). Transient neurologic dysfunction was noted in 6 (5.5%) patients. Mean duration of hypothermic circulatory arrest was 31.2 +/- 6.6 minutes and selective cerebral perfusion was 65.3 +/- 20.9 minutes. Reoperation for bleeding was required in 3 (2.8%) patients and prolonged intubation in 15 (13.8%). Median intensive care unit stay was 3 days (interquartile range 2-4; range, 1 to 108) and hospital stay was 9 (interquartile range 8-15; range, 5 to 108). The trifurcated graft technique results in low rates of perioperative mortality, temporary neurologic dysfunction, and stroke. It may reduce cerebral embolization as it requires no instrumentation of the aortic arch to establish selective cerebral perfusion and, although it mandates hypothermic circulatory arrest to place the graft, this interval is reliably brief enough to fall within accepted safe limits. This strategy leaves no residual arch tissue behind, and allows placement of an elephant trunk proximal to one or more arch vessels if anatomically indicated.

Repair of the symptomatic aberrant aortic arch aneurysm without hypothermic circulatory arrest

Manifestation of anomalies of the aortic arch in adulthood has been reported in the literature. The symptoms stem from the compression of the trachea and esophagus or peripheral arterial ischemia associated with coarctation of the aberrant arch. The aberrant arch aneurysms are subject to complications of rupture or dissection. This may be the first reported case of a large complex aneurysm of an anomalous aortic arch resected on cardiopulmonary bypass without any period of hypothermic circulatory arrest or distal ischemia.

Ph-stat versus alpha-stat perfusion strategy during experimental hypothermic circulatory arrest: a microdialysis study

Background The superiority of the pH-stat to the α-stat acid-base strategy during cardiopulmonary bypass as a neuroprotective method during hypothermic circulatory arrest is still controversial. In the present study, brain metabolism and outcome have been evaluated in a surviving model of experimental hypothermic circulatory arrest. Methods Twenty pigs undergoing 75-minutes of hypothermic circulatory arrest at a brain temperature of 18°C were randomly assigned to the α-stat (n = 10) or pH-stat (n = 10) strategy during cardiopulmonary bypass. Results The 7-day survival rate was 90% (9 of 10) in the pH-stat group and 10% (1 of 10) in the α-stat group. At the end of cooling, pH-stat strategy was associated with significantly lower brain lactate and pyruvate concentrations and brain lactate-glucose ratio. After reperfusion, brain concentrations of glycerol, lactate, pyruvate, and lactate-glucose ratio were significantly lower in the pH-stat group. This strategy was associated with a faster rise of brain tissue temperature and reoxygenation on reperfusion, which is likely secondary to improved cerebral perfusion. Conclusions During cardiopulmonary bypass before and after a period of hypothermic circulatory arrest, acid-base management according to the pH-stat principles seemed to be associated with less derangements in cerebral metabolism, lower intracranial pressures, and excellent behavioral recovery and survival outcome. Because there is strong evidence of the beneficial metabolic effects related to this method, further studies using an experimental model of combined HCA and embolic brain injury are required to exclude a possible increased risk of cerebral embolism associated with the pH-stat strategy.

Topical head cooling during rewarming after experimental hypothermic circulatory arrest

Background The aim of this study was to evaluate the potential neuroprotective effect of topical head cooling during the first 2 postoperative hours after experimental hypothermic circulatory arrest. Methods Twenty pigs underwent a 75-minute period of hypothermic circulatory arrest and were randomly assigned to rewarming to 37°C or to undergo topical cooling of the head for 2 hours from the start of rewarming followed by a period of external rewarming to 37°C. Results The 7-day survival rate was 70% in the control group and 60% in the topical head cooling group. Despite brain tissue oxygenation, intracranial pressures, mixed oxygen venous saturation, oxygen consumption, and extraction tended to be favorable in the topical head cooling group as a clear effect of mild hypothermia. The latter group had significantly higher postoperative brain lactate and pyruvate ratios, and lactate and glucose ratios. Furthermore, the topical head cooling group had worse fluid balance throughout the postoperative period. Brain histopathologic scores were comparable with the study groups, but among 7-days survivors these scores tended to be worse in the topical head cooling group. Conclusions Topical cooling of the head during the first 2 postoperative hours after experimental hypothermic circulatory arrest does not appear to provide any neuroprotective effect.

Fructose-1,6-bisphosphate for improved outcome after hypothermic circulatory arrest in pigs

Objective: Fructose-1,6-bisphosphate is a high-energy intermediate in the anaerobic metabolism. It enhances glycolysis, preserves cellular adenosine triphosphate, and prevents the increase of intracellular calcium during ischemia. The potential neuroprotective effect of fructose-1,6-bisphosphate during hypothermic circulatory arrest was evaluated in a surviving porcine model. Methods: Twenty-four pigs were randomly assigned to receive two intravenous infusions of either fructose-1,6-bisphosphate (500 mg/kg) or saline solution. The first infusion was given immediately before a 75-minute period of hypothermic circulatory arrest and the second was given immediately after hypothermic circulatory arrest. Results: The 7-day survivals were 83.3% in the fructose-1,6-bisphosphate group and 41.7% in the control group (P =.09). The treated animals had significantly better postoperative behavioral scores. The administration of fructose-1,6-bisphosphate was associated with higher venous phosphate and sodium levels, lower venous ionized calcium levels, higher blood osmolarity, and a better fluid balance. Intracranial pressure and venous creatine kinase isoenzyme MB were significantly lower in the fructose-1,6-bisphosphate group during rewarming (P =.01 and P =.001, respectively). Among the treated animals, brain glucose, pyruvate and lactate levels tended to be higher, brain glycerol levels tended to be lower, and the histopathologic score of the brain was significantly lower (P =.04). Conclusions: Intravenous administration of fructose-1,6-bisphosphate at 500 mg/kg before and after hypothermic circulatory arrest in a surviving porcine model was associated with better survival, behavioral outcome, and histopathologic score. The observed lower blood creatine kinase isoenzyme MB and brain glycerol levels and the higher brain glucose, pyruvate, and lactate levels in the fructose-1,6-bisphosphate group suggest that this drug has supportive effects on myocardial and brain metabolisms.J Thorac Cardiovasc Surg 2003;125:686-98

S100β and NSE: Stroke surrogate signals or natal neural noise?

S100β and NSE: Stroke surrogate signals or natal neural noise?

EEG burst recovery is predictive of brain injury after experimental hypothermic circulatory arrest

Objective--To evaluate whether electroencephalography (EEG) recovery could be considered a reliable marker of brain injury after experimental hypothermic circulatory arrest (HCA). Design--Cortical electrical activity was registered before and after a 75-min period of HCA in 27 pigs that survived 7 days after the experiment. The sum of EEG bursts was counted as a percentage of the sum of artifact-free bursts and suppressions, and this percentage was used as a measure of EEG activity in the analysis. Results--Brain infarction developed in 13 animals (48.1%), in 12 cases (44.4%) having involved the cortex, in 1 case the thalamus (3.7%) and in another the hippocampus (3.7%). The mean EEG burst percentage significantly correlated with the total brain histopathological score (ρ = −0.588, P = 0.001). EEG burst percentage from the 2 h 20 min to the 7 h 20 min interval correlated with the total brain histopathological score and with the cortex, brainstem and cerebellum scores. The mean EEG burst percentage rate was higher, but not significantly, among the animals without brain infarction (38.5% vs 32.4%), but such a difference was significant at the 3 h 20 min postoperative interval (P = 0.02). The mean EEG burst percentage significantly correlated with brain glucose concentration at the 1 h interval (ρ = 0.387; P = 0.046), brain lactate concentration at the 2 h interval (ρ = −0.431; P = 0.025), and the brain lactate/glucose ratio at the 1 h 30 min interval from the start of rewarming (ρ = −0.433; P = 0.024). Conclusion--A decreased EEG burst percentage seems to be associated with an increased risk of developing histologically evident brain ischemic injury in the cortex, brainstem and cerebellum after experimental HCA.

Perioperative risk factors for mortality in patients with acute type a aortic dissection

Background This study was undertaken to identify the perioperative risk factors for death in patients with acute type A aortic dissection (AADA). Methods Between 1993 and 2001, 108 consecutive patients (86 men; mean age, 53 years) underwent emergent operations for AADA. All patients but 2 underwent replacement of the ascending aorta with an open distal anastomosis during a period of hypothermic circulatory arrest. In addition, 22 patients had hemiarch and 5 had total arch replacement. Aortic root was replaced in 20 and repaired with gelatin-resorcinol-formaldehyde glue in 39 patients; aortic valve was separately replaced in 3, resuspended in 24, and remained untouched in 22 patients. Results Overall in-hospital mortality was 25%. Mortality rate was significantly higher in patients with preoperative dissection complications than in those without (21/36 [58%] vs 6/72 [8%], p < 0.001). In multivariate analysis, predictors of mortality were presence of rupture, renal failure, and intestinal malperfusion, duration of cardiopulmonary bypass ≥200 minutes, blood loss ≥500 mL, and transfusion of blood ≥4 units. Location of the intimal tear, extent of the replacement, type of the aortic root repair, and duration of hypothermic circulatory arrest did not emerge as predictors of mortality. Conclusions Major determinants of surgical mortality in patients with AADA are preoperative complications. Earlier diagnosis remains essential to improve the survival rate.

Potential neuroprotective benefits of erythropoietin during experimental hypothermic circulatory arrest

Objective: Recent studies have shown that erythropoietin protects neurons from glutamate toxicity and ischemia. This study was performed to evaluate the potential neuroprotective effect of erythropoietin during experimental hypothermic circulatory arrest. Methods: Twenty pigs were randomized to receive intravenously either 500 IU/kg recombinant human erythropoietin or saline before a 75-minute period of hypothermic circulatory arrest at an intracerebral temperature of 18°C. Results: After the administration of erythropoietin, its concentration in the cerebrospinal fluid increased 4.5-fold 8 hours after the start of rewarming, whereas it did not increase in control animals. The 7-day survival rate was 60% in the erythropoietin group and 70% in the control group (P = 1.0). No significant differences were observed between the study groups in terms of electroencephalography, behavioral score, and histopathologic score. The erythropoietin group had higher vascular resistance and mean arterial pressure values, lower intracerebral concentrations of glutamate and glycerol, higher brain tissue oxygen tension, and lower apoptotic index. Conclusions: Administration of 500 IU/kg erythropoietin intravenously before hypothermic circulatory arrest was followed by an increased erythropoietin concentration in the cerebrospinal fluid. Although previous studies have demonstrated neuroprotective effects of erythropoietin during brain ischemia, the present study, using a chronic porcine model, failed to show any significant benefit after administration of erythropoietin in terms of mortality or brain histopathology. Lower intracerebral concentrations of glutamate and glycerol, higher brain tissue oxygen tension, and lower apoptotic index observed in the erythropoietin group, however, suggest that a distinct neuroprotective effect of erythropoietin might be achieved at different dosages and timing of administration.J Thorac Cardiovasc Surg 2002;124:714-23

Increase of Intracranial Pressure after Hypothermic Circulatory Arrest in a Chronic Porcine Model

Objective: An increase in intracranial pressure has been shown to threaten the outcome of patients with ischemic or traumatic brain injury. Its impact on the outcome of pigs undergoing hypothermic circulatory arrest has been evaluated in this study. Design: Fifty-six pigs underwent a 75-min period of hypothermic circulatory arrest at 20°C. Intracranial pressure, cerebral microdialysis, hemodynamic and metabolic parameters were monitored throughout the experiment. The animals were allowed to survive until the 7th postoperative day and, then, electively killed. Results: The 7-day survival rate was 60.7%, and among survivors, 20 of them (58.8%) developed brain infarction. A significant increase in intracranial pressure as compared with the baseline level was observed since the end of cooling ( p = 0.047) and the difference became larger during all the postoperative intervals ( p < 0.0001). Animals that died postoperatively tended to have higher intracranial pressure levels during all the postoperative intervals, but such a difference reached significance only at the 4-h postoperative interval ( p = 0.040). The same tendency was observed among animals that survived until the 7th postoperative day and that developed brain infarction or not, but the difference between these two groups did not reach statistical significance. The animals that died or developed postoperatively brain infarction had higher intracranial pressure values postoperatively as compared with those that survived without developing brain infarction and such a difference reached significance at the 2-h ( p = 0.015) and 4-h postoperative intervals ( p = 0.035). The peak intracranial pressure was 17.2 mmHg (IQR, 13.7-20.8) in animals that died or developed brain infarction and 14.1 mmHg (IQR, 11.8-16.4) in those that survived 7 days without developing brain infarction ( p = NS). Conclusion: Intracranial pressure increases significantly after 75 min of experimental hypothermic circulatory arrest and such an increase is associated with a high risk of postoperative death and brain infarction.

The N-methyl-D -aspartate antagonist memantine has no neuroprotective effect during hypothermic circulatory arrest: A study in the chronic porcine model

Glutamate excitotoxicity has an important role in the development of brain injury after prolonged hypothermic circulatory arrest. The goal of the present study was to determine the potential efficacy of memantine, an N -methyl-D -aspartate receptor antagonist, to mitigate cerebral injury after hypothermic circulatory arrest. Twenty pigs (23-33 kg) were randomly assigned to receive memantine (5 mg/kg) or placebo in a blinded fashion before a 75-minute period of hypothermic circulatory arrest at 20 degrees C. Hemodynamic, electroencephalographic, and metabolic monitoring were carried out. The intracerebral concentrations of glucose, lactate, glutamate, and glycerol were measured by means of enzymatic methods on a microdialysis analyzer. Daily behavioral assessment was performed until the animals died or were put to death on day 7. Histologic analysis of the brain was carried out in all animals. In the memantine group, 5 of 10 animals survived 7 days compared with 9 of 10 in the placebo group. The median behavioral score at day 7 was 3.5 in the memantine group and 7.5 in the placebo group (P >.2). Among the surviving animals, medians were 9.0 and 8.0 on day 7 (P >.2), respectively. The medians of recovered electroencephalographic bursts were equal in both groups. The median of total histopathologic score was 16 in the memantine group and 14 in the placebo group (P >.2). There was a negative correlation between glutamate levels and electroencephalographic burst recovery (tau = -0.377, P =.043). A positive correlation was found between the highest individual glutamate value and histopathologic score (tau = 0.336, P =.045). The present study demonstrates that memantine has no neuroprotective effect after hypothermic circulatory arrest in the pig. In addition, we have shown the accuracy of cerebral glutamate measurements to predict histopathologic injury after hypothermic ischemia.

The Role of Cerebral Microdialysis in Predicting the Outcome after Experimental Hypothermic Circulatory Arrest

Objective –To evaluate whether and which of the cerebral microdialysis parameters are predictive of postoperative outcome after an experimental 75-min period of hypothermic circulatory arrest (HCA) in a chronic porcine model. Design –Seventy-four juvenile female pigs underwent a 75-min period of HCA at 20°C. A microdialysis catheter was placed into the cortex gray matter and brain extracellular concentrations of glucose, lactate, glycerol and glutamate were measured throughout the experiment by enzymatic methods using a microdialysis analyzer. Surviving animals were sacrificed on the 7th postoperative day and histopathological examination of the brain was performed. Results –Brain glucose concentrations were higher in animals that survived ( p = 0.017), especially from the 90-min until the 7-h interval after the start of rewarming. The blood venous concentrations of glucose were also higher among survivors, and correlated significantly with the brain glucose levels at 2-h and 4-h intervals after the start of rewarming. Higher concentrations of brain lactate, glycerol and glutamate were observed throughout the study among animals that died postoperatively. Brain glutamate and glycerol concentrations were significantly, negatively correlated with brain glucose concentrations. The lactate/glucose ratio was significantly lower among survivors during the postoperative period ( p = 0.014). Furthermore, brain glucose concentrations were higher and brain glycerol concentrations lower among the animals that did not develop brain infarction, but such differences did not reach statistical significance. Conclusion –Cerebral microdialysis is a useful tool for cerebral monitoring during experimental HCA. Low brain glucose concentrations and high brain lactate/glucose ratios after HCA are strong predictors of postoperative death. Brain glucose concentrations are negatively correlated with brain glycerol and glutamate concentrations.

Leukocyte filtration improves brain protection after a prolonged period of hypothermic circulatory arrest: A study in a chronic porcine model

Background: Ischemic cerebral injury follows a well-attested sequence of events, including 3 phases: depolarization, biochemical cascade, and reperfusion injury. Leukocyte infiltration and cytokine-mediated inflammatory reaction are known to play a pivotal role in the reperfusion phase. These events exacerbate the brain injury by impairing the normal microvascular perfusion and through the release of cytotoxic enzymes. The aim of the present study was to determine whether a leukocyte-depleting filter (LeukoGuard LG6, Pall Biomedical, Portsmouth, United Kingdom) could improve the cerebral outcome after hypothermic circulatory arrest. Methods: Twenty pigs (23-30 kg) were randomly assigned to undergo cardiopulmonary bypass with or without a leukocyte-depleting filter before and after a 75-minute period of hypothermic circulatory arrest at 20°C. Electroencephalographic recovery, S-100β protein levels, and cytokine levels (interleukin 1β, interleukin 8, and tumor necrosis factor α) were recorded up to the first postoperative day. Postoperatively, all animals were evaluated daily until death or until electively being put to death on day 7 by using a quantitative behavioral score. A postmortem histologic analysis of the brain was carried out on all animals. Results: The rate of mortality was 2 of 10 in the leukocyte-depletion group and 5 of 10 in control animals. The risk for early death in control animals was 2.5 (95% confidence interval, 0.63-10.0) times higher than that of the leukocyte-depleted animals. The median behavioral score at day 7 was higher in the leukocyte-depletion group (8.5 vs 3.5; P = .04). The median of total histopathologic score was 8.5 in the leukocyte-depletion group and 15.5 in the control group (P = .005). Conclusion: A leukocyte-depleting filter improves brain protection after a prolonged period of hypothermic circulatory arrest. (J Thorac Cardiovasc Surg 2000;120:1131-41)

The atherosclerotic aorta at aortic valve replacement: surgical strategies and results.

Aortic valve replacement in patients with severe atherosclerosis of the ascending aorta poses technical challenges. The purpose of this study was to examine operative strategies and results of aortic valve replacement in patients with a severely atherosclerotic ascending aorta that could not be safely crossclamped. From January 1990 to December 1998, 4983 patients had aortic valve surgery; of these, 62 (1.2%) patients had a severely atherosclerotic ascending aorta and required hypothermic circulatory arrest to facilitate aortic valve replacement. They form the study group. All patients had hypothermic circulatory arrest, but several different strategies were used to manage the ascending aorta. These techniques included aortic valve replacement with the use of hypothermic circulatory arrest (39%), ascending aortic endarterectomy (26%), ascending aortic replacement (19%), aortic inspection and crossclamping during hypothermic circulatory arrest (10%), and balloon occlusion of the ascending aorta (6%). Duration of hypothermic circulatory arrest was substantially longer for patients having aortic valve replacement with hypothermic circulatory arrest than for all other strategies. Hospital mortality was 14%, and 10% of patients had strokes. Increasing New York Heart Association functional class and impaired left ventricular function were risk factors for hospital mortality. Choice of operative technique did not influence patient outcome; however, no patient who underwent replacement of the ascending aorta had a stroke. Aortic valve replacement in patients with severe atherosclerosis of the ascending aorta is associated with increased operative morbidity and mortality. Complete aortic valve replacement during hypothermic circulatory arrest, the "no-touch" technique, requires a prolonged period of circulatory arrest. Ascending aortic replacement is a preferred technique, as it requires a short period of hypothermic circulatory arrest and results in comparable mortality with a low risk of stroke.

Lamotrigine improves cerebral outcome after hypothermic circulatory arrest: A study in a chronic porcine model

Background: Glutamate excitotoxicity has an important role in the development of brain injury after prolonged hypothermic circulatory arrest. The goal of the present studies was to determine the potential efficacy of lamotrigine, an Na+ channel blocker, to mitigate cerebral injury after hypothermic circulatory arrest. Methods: Sixteen pigs (21-27 kg) were randomly assigned to receive lamotrigine (20 mg/kg) or placebo in a blinded fashion before a 75-minute period of hypothermic circulatory arrest (20°C). Hemodynamic, electroencephalographic, and metabolic monitoring were carried out. S-100β protein was determined up to the first postoperative morning. Daily behavioral assessment was performed until the animal died or was put to death on day 7. Histologic analysis of the brain was carried out in all animals. Results: Complete behavioral recovery was seen in 5 of 8 (63%) animals after lamotrigine administration, compared with 1 of 8 (13%) in the placebo group (P =.02). Among the animals that survived for 7 days, the median behavioral score was higher in the lamotrigine group (8 vs 7, P =.02). The medians of recovered electroencephalographic bursts in the lamotrigine group were higher than those in the placebo group 4 1/2 hours after the start of rewarming (P =.01). The median S-100β level was lower in the lamotrigine group (0.01 μg/L) than in placebo controls (0.1 μg/L) 20 hours after the start of rewarming (P =.01). The median of total histopathologic score was 5.5 in the lamotrigine group and 7.5 in the placebo group (P =.06). Conclusions: The present data suggest that lamotrigine improves neurologic outcome after a prolonged period of hypothermic circulatory arrest. (J Thorac Cardiovasc Surg 2000;120:247-55)

Intermittent Retrograde Cerebral Perfusion During Prolonged Period of Hypothermic Circulatory Arrest: A Study in a Chronic Porcine Model

Previous studies have shown that although retrograde cerebral perfusion (RCP) improves cerebral outcome during hypothermic circulatory arrest (HCA), RCP exposes the brain to subsequent edema. In this study, we have compared intermittent RCP (I-RCP) with continuous RCP (C-RCP) and HCA alone to determine whether the rate of fluid sequestration can be decreased without losing the beneficial effects of RCP. Eighteen pigs were randomly assigned to undergo 75 min of I-RCP, C-RCP or HCA at 20 degrees C. Hemodynamic and metabolic measurements were carried out for upto 20 h. Behavioral assessments were examined until day 7, when histopathologic analysis of the brain was performed. The median amount of fluid sequestered was 145 ml after C-RCP and -50 ml after I-RCP (p = 0.04). The mean brain weight of the animals that died within the first postoperative day was significantly higher than that in electively sacrificed animals in the C-RCP group (p = 0.04). These data suggest that if RCP is implemented intermittently, the rate of cerebral edema can be decreased, without compromising the benefits of this strategy.