Pharmacokinetics of 0.5% levobupivacaine following ilioinguinal-iliohypogastric nerve blockade in children.

BACKGROUND: Bupivacaine (2 mg kg(-1)) has been recommended for blockade of the ilioinguinal and iliohypogastric nerves in paediatric patients undergoing inguinal surgery. We determined the plasma concentrations of levobupivacaine following ilioinguinal-iliohypogastric block. METHODS: Twenty children scheduled for elective surgery for inguinal surgery received 2 mg kg(-1) of 0.5% levobupivacaine. Surgical anaesthesia was maintained with mask inhalation of oxygen, nitrous oxide and sevoflurane. Venous blood samples were drawn at regular intervals up to 2 h and plasma was separated. Total venous plasma concentrations were determined by gas chromatography. Bupivacaine concentrations from a study with a similar protocol were used as historical controls for comparison. RESULTS: The groups were similar with respect to age, weight and dosage of local anaesthetic. The initial distribution half-time (Talpha), the peak plasma concentration (Cmax) achieved, the time to the peak plasma concentration were similar (Tmax), and the mean areas under the concentration time curve (AUC) were similar between the two local anaesthetics. CONCLUSIONS: Levobupivacaine and bupivacaine are equally absorbed to similar maximum concentrations.

Pharmacokinetics of 0.75% ropivacaine and 0.5% bupivacaine after ilioinguinal-iliohypogastric nerve block in children.

BACKGROUND: Blockade of the ilioinguinal and iliohypogastric nerves is a useful procedure in paediatric patients undergoing inguinal surgery. Bupivacaine 2 mg kg-1 has been recommended for this block. We compared the plasma concentrations of ropivacaine and bupivacaine following an ilioinguinal-iliohypogastric block. METHODS: Forty children scheduled for elective inguinal surgery were randomized to receive 2 mg kg-1 of either 0.75% ropivacaine or 0.5% bupivacaine. Surgical anaesthesia was maintained with mask inhalation of oxygen, nitrous oxide and sevoflurane. Venous blood samples were drawn at regular intervals for up to 2 h and plasma was separated. Total venous plasma concentrations were determined by gas chromatography. RESULTS: The groups were similar with respect to age, weight and dose of local anaesthetic. The peak plasma concentration achieved was significantly higher in the bupivacaine group compared with the ropivacaine group (2.2 vs 1.2 micrograms ml-1, P = 0.025). The time to peak plasma concentration was significantly shorter in the bupivacaine group (24 vs 35 min, P = 0.024). The initial distribution half time of bupivacaine was significantly shorter (3.6 vs 6.5 min, P = 0.020) compared with that of ropivacaine. CONCLUSIONS: Bupivacaine is more rapidly absorbed from the injection site and leads to higher plasma concentrations than ropivacaine.

Apoptotic activity is increased in brain cortex infarct after hypothermic circulatory arrest in a porcine model.

OBJECTIVE: It has been shown that apoptosis contributes to neuronal cell death after ischemia, and we evaluated the degree of apoptotic activity occurring in brain cortex of pigs after hypothermic circulatory arrest (HCA). DESIGN: Thirty-one pigs underwent 75 min of HCA at 20 degrees C. Histological examination of the brain was performed, and slides of brain cortex were evaluated for apoptotic activity by the TUNEL method. RESULTS: Ten animals died during the first postoperative day and 21 survived until the seventh postoperative day. Brain cortex infarcts were found in animals that survived 7 days and these were included in this study. The median histopathological score among animals that died on the first postoperative day was 3.0 (range, 2-4), whereas it was 4.0 (range, 2-4) among survivors (p = 0.019). The apoptotic index was particularly high in the area of the infarct, whereas only a few TUNEL-stained cells were observed in noninfarcted areas. The apoptotic index was nil in all pigs that died in the first postoperative period, whereas it was 2.0 (range, 0-6) among the animals that survived until the seventh postoperative day (p < 0.0001). CONCLUSION: The apoptotic index was significantly increased in brain cortex infarcts of animals that survived 7 days after HCA, whereas only a few apoptotic cells were observed in noninfarcted areas of these animals as well as in animals that died on the first postoperative day. Further studies are required to elucidate the timing of development of brain infarction after HCA and whether neuroprotective strategies targeting the apoptotic process may mitigate brain damage.

Determinants of mortality after hypothermic circulatory arrest in a chronic porcine model.

OBJECTIVE: Beside neurological morbidity, mortality is a relevant end-point of experimental porcine model of hypothermic circulatory arrest (HCA) and this study was conducted to identify the determinants for postoperative death. METHODS: One hundred and thirty-five pigs underwent a 75-min period of HCA at 20 degrees C to evaluate the efficacy of different methods of cerebral protection. RESULTS: Survival rate at 7-day follow-up was 52%. Lower oxygen extraction, oxygen consumption/kg, and venous lactate at the end of cooling and higher oxygen delivery rates were significantly associated with better outcome. Logistic regression showed that the oxygen consumption/kg at the end of cooling was the only predictor of mortality (P=0.046). Animals with an oxygen consumption/kg rate less than 1.43 ml/min per kg at the end of cooling had a mortality rate of 28%, whereas it was 50% among animals with an oxygen consumption/kg rate higher or equal to 1.43 ml/min per kg (P=0.020). The latter had even an increased 1-day mortality rate (40% vs. 26%) (P not significant). The mortality rate after anesthesia induction with ketamine plus 100% of oxygen was 38%, 45% after anesthesia induction with ketamine plus 35% oxygen, and 53% after anesthesia with medetomidine plus 35% oxygen (P not significant). CONCLUSIONS: Parameters of oxyhemodynamics should be monitored especially from the induction of anesthesia to the end of cooling before a 75-min period of HCA. The use of medetomidine and/or 35% of oxygen at induction of anesthesia should be avoided in favor of ketamine plus 100% of oxygen.

The haemodynamic effects of losartan after right ventricle infarct in young pigs.

The effect of an intravenous bolus injection of the type 1 angiotensin II receptor antagonist, losartan on haemodynamics after right heart infarct was studied in an experimental setting. Right heart infarct was induced in twelve young swine and losartan was given in a bolus intravenous dose one hr later to five animals, while seven animals served as controls. Haemodynamics were then followed for one hr at 15 min intervals. Losartan was subsequently shown to decrease central venous pressure and wedge pressure, while cardiac output, left ventricle stroke work and stroke volume all showed improvement. Compared to the control animals, pulmonary vascular resistance, systemic vascular resistance and systemic pressures were unaffected by the drug, as was heart rate. The use of losartan shortly after right heart infarct reduced both right and left heart preload as well as inducing an improvement in cardiac performance. At the same time, systemic pressures and heart rate were maintained. We conclude that an inhibition of angiotensin II action may be a benefit in the treatment of right heart failure symptoms during the first hours after right heart infarct.

Inhaled nitric oxide effectively decreases right heart afterload following right heart infarct in pigs.

OBJECTIVE: To test the hypothesis that nitric oxide is beneficial in acute right heart failure after right ventricle infarct. Right ventricle infarct results in a decrease in right heart function with a subsequent reduction in ejection fraction and cardiac index. The pulmonary circulation is compromised as the right ventricle weakens, and the resulting stasis and further weakening of the ventricle present clinically as an increase in right heart afterload. Pulmonary vasodilation should ease these hemodynamic symptoms of right heart infarct. DESIGN: Ten 3-4-month-old pigs were chosen as experimental animals. All animals were cannulated, a sternotomy was performed and branches of the right main coronary were ligated to cause infarct of the right ventricle. After a 4-h stabilization period, all animals received fluid preload with a dextrose-based solution after which control hemodynamic measurements were recorded. Treatment with inhaled nitric oxide was begun at progressive concentrations and hemodynamic measurements recorded at 30-min intervals. RESULTS: Nitric oxide treatment significantly reduced right heart afterload, which was also apparent as a reduction in left heart preload. A significant deterioration was observed in cardiac output as well as in left and right ventricle stroke work indices. CONCLUSION: The use of nitric oxide in this model of right heart infarct in previously healthy young swine effected a decrease in both right heart afterload and left heart preload, with an overall deterioration in global hemodynamics.

The N-methyl-D-aspartate antagonist memantine has no neuroprotective effect during hypothermic circulatory arrest: a study in the 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 study was to determine the potential efficacy of memantine, an N -methyl-D -aspartate receptor antagonist, to mitigate cerebral injury after hypothermic circulatory arrest. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Myocardial preservation during coronary surgery with and without cardiopulmonary bypass.

BACKGROUND: There is increased interest in coronary artery bypass grafting (CABG) without cardiopulmonary bypass (CPB), although the preservation of the myocardium under such circumstances has not been properly investigated. The aim of this randomized study was to compare the changes in myocardial metabolism during CABG with and without CPB. METHODS: Myocardial energy metabolism and tissue injury during CABG was monitored in a series of 22 patients (11 with and 11 without CPB). RESULTS: The maximum myocardial lactate production was significantly higher (p = 0.02) in the group operated with CPB (0.56 mmol/L) than without it (0.17 mmol/L). A similar phenomenon was seen in the transcardiac pH differences (0.085 and 0.034 with and without CPB, p = 0.007). The postoperative peak values of creatine kinase-MB mass (15.1 vs 6.3 microg/L) and troponin I (13.8 vs 5.2 microg/L) were significantly higher (p < 0.001 and p = 0.008) with than without CPB. CONCLUSIONS: CABG on a beating heart is associated with better myocardial energy preservation and less myocardial damage compared with conventional CABG with CPB and intermittent antegrade mild hypothermic blood cardioplegia.

Reversible ischemic inhibition of F(1)F(0)-ATPase in rat and human myocardium.

The physiological role of F(1)F(0)-ATPase inhibition in ischemia may be to retard ATP depletion although views of the significance of IF(1) are at variance. We corroborate here a method for measuring the ex vivo activity of F(1)F(0)-ATPase in perfused rat heart and show that observation of ischemic F(1)F(0)-ATPase inhibition in rat heart is critically dependent on the sample preparation and assay conditions, and that the methods can be applied to assay the ischemic and reperfused human heart during coronary by-pass surgery. A 5-min period of ischemia inhibited F(1)F(0)-ATPase by 20% in both rat and human myocardium. After a 15-min reperfusion a subsequent 5-min period of ischemia doubled the inhibition in the rat heart but this potentiation was lost after 120 min of reperfusion. Experiments with isolated rat heart mitochondria showed that ATP hydrolysis is required for effective inhibition by uncoupling. The concentration of oligomycin for 50% inhibition (I(50)) for oxygen consumption was five times higher than its I(50) for F(1)F(0)-ATPase. Because of the different control strengths of F(1)F(0)-ATPase in oxidative phosphorylation and ATP hydrolysis an inhibition of the F(1)F(0)-ATPase activity in ischemia with the resultant ATP-sparing has an advantage even in an ischemia/reperfusion situation.

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 degrees 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 degrees C. Electroencephalographic recovery, S-100beta protein levels, and cytokine levels (interleukin 1beta, interleukin 8, and tumor necrosis factor alpha) 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.

Pharmacokinetics of 0.2% ropivacaine and 0.2% bupivacaine following caudal blocks in children.

BACKGROUND: Ropivacaine is the first S-enantiomer aminoamide local anaesthetic in clinical use, and has been found to be less toxic than bupivacaine. Caudal ropivacine has been shown to cause less motor blockade and longer duration of analgesia in the postoperative period than bupivacaine in children. Plasma levels of ropivacaine and bupivacaine have not been previously compared in children. This study was undertaken to compare the total venous plasma concentrations of similar doses of ropivacaine and bupivacaine following caudal administration. METHODS: Blood samples were obtained to determine the total venous plasma levels of the used local anaesthetic in 30 children, aged 2.3-8.7 years, ASA I, given 1 ml x kg of either 0.2% ropivacaine or 0.2% bupivacaine in a prospective, randomised manner. RESULTS: There were no differences in the individual peak plasma concentrations achieved. Time to the measured peak plasma concentration was significantly shorter in the bupivacaine group. The plasma concentrations of bupivacaine were significantly lower than for ropivacaine at 60, 90 and 120 min after the block. CONCLUSION: Absorption and tissue distribution of ropivacaine is slower than for bupivacaine following caudal administration in children.

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 degrees C). Hemodynamic, electroencephalographic, and metabolic monitoring were carried out. S-100beta 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-100beta level was lower in the lamotrigine group (0.01 microg/L) than in placebo controls (0.1 microg/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.

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.

Is maintained cranial hypothermia the only factor leading to improved outcome after retrograde cerebral perfusion? An experimental study with a chronic porcine model.

BACKGROUND: Previous studies have shown that retrograde cerebral perfusion can improve neurologic outcome after prolonged hypothermic circulatory arrest. Here we have compared two temperatures of retrograde cerebral perfusion (15 degrees C and 25 degrees C) with hypothermic circulatory arrest at systemic hypothermia of 25 degrees C to clarify whether the possible benefit of retrograde cerebral perfusion may only be due to improved cooling effect. METHODS: Eighteen pigs (23-27 kg) were randomly assigned to undergo 15 degrees C retrograde cerebral perfusion at systemic hypothermia of 25 degrees C, 25 degrees C retrograde cerebral perfusion at 25 degrees C systemic hypothermia, or hypothermic circulatory arrest at 25 degrees C for 40 minutes. Flow was adjusted to maintain superior vena cava pressure at 20 mm Hg during retrograde cerebral perfusion. Hemodynamic, electrophysiologic, metabolic, and temperature monitoring were performed until 4 hours after the start of rewarming. Daily behavioral assessment was done until death or until the animals were killed on day 7. Histopathologic analysis of the brain was carried out on all animals. RESULTS: Epidural temperatures were lower in the 15 degrees C retrograde cerebral perfusion group during the intervention (P <.05). In the 15 degrees C retrograde cerebral perfusion group, 4 (67%) of 6 animals survived for 7 days compared with 3 (50%) of 6 in both the 25 degrees C retrograde cerebral perfusion and hypothermic circulatory arrest groups. The median total histopathologic score was 5 in the 15 degrees C retrograde cerebral perfusion group and 7 in the 25 degrees C retrograde cerebral perfusion group (P =.04). CONCLUSIONS: These findings suggest that enhanced cranial hypothermia is the major beneficial factor of retrograde cerebral perfusion when careful attention is paid to its implementation.

The effect of aminophylline on right heart function in young pigs after ligation of the right coronary artery.

An experimental model of right heart failure was developed to determine the effects of fluid loading and aminophylline on right heart function. We hypothesised that aminophylline would specifically improve right heart function through a decrease in pulmonary vascular resistance and, possibly, an increase in cardiac contractility. Right heart infarct was induced in ten experimental pigs and seven control pigs by ligating branches of the right coronary artery. The effect of fluid loading with a colloid solution and subsequent bolus doses of aminophylline on haemodynamics was observed. Fluid loading improved haemodynamics as expected. Aminophylline transiently improved cardiac index and pulmonary vascular resistance, but simultaneously caused an increase in heart rate and a decrease in stroke volume. Although aminophylline may reduce right heart afterload, it did not improve overall cardiac function in this experimental model of right heart infarction.

The hemodynamic effects of adenosine infusion after experimental right heart infarct in young swine.

The use of a vasodilator selective to the pulmonary circulation may be beneficial in cases with right-ventricle failure, as it will decrease right-heart afterload without concurrent systemic hypotension. Adenosine has recently been advocated as such a drug, although its clinical efficacy in this respect is still in question. We therefore devised an experimental protocol of right-heart infarct to test the efficacy of adenosine in alleviating symptoms of right-heart failure. Right-heart infarct was induced experimentally in 17 young pigs. After hemodynamics had stabilized, preload was optimized with a dextrose-based colloid solution. A continuous infusion of adenosine was then begun at doses of 25, 50, 75, and 100 microg/kg/min in a study group of 10 animals, while the remaining seven were monitored as controls. Hemodynamic parameters were followed throughout the study, with particular attention paid to pulmonary and systemic vascular resistance indices (PVRI and SVRI), right ventricle ejection fraction (REF), cardiac index (CI), and heart rate (HR). Cardiac index (CI) showed a tendency to increase during the adenosine infusion, as did REF and stroke index (SI), whereas PVRI and mean pulmonary pressure (MPAP) were decreased. There was a marked decrease in SVRI as a result of the adenosine, as there was in mean arterial pressure at the higher infusion rates. HR remained unchanged by the infusion. Discontinuation of the drug resulted in a rapid increase in MAP, SVRI, MPAP, HR, left ventricle stroke work index (LVSWI), and PVRI and in a modest decrease in CI. The continuous infusion of adenosine appears to cause an effective arterial vasodilation, with a consequent unloading of right-heart afterload. Its use may be beneficial in the treatment of increased pulmonary vascular resistance after right-heart failure.

Serum S-100beta protein predicts brain injury after hypothermic circulatory arrest in pigs.

OBJECTIVE: Serum S-100beta protein is suggested to be a neurobiochemical marker of brain injury after cardiac and aortic arch surgery. The aim of the present study was to investigate the predictive value of S-100beta protein with respect to histopathological analysis of the brain after a prolonged period of hypothermic circulatory arrest (HCA). METHODS: Eighteen pigs (21 to 31 kg) underwent a 75 min period of HCA at 20 degrees C. Serum concentrations of S-100beta were assayed in mixed venous blood before and 2, 4, 7 and 20 h after HCA. A semiquantitative post-mortem histopathological analysis scoring all main regions of the brain was carried out in every animal. RESULTS: All animals were stable during and after cardiopulmonary bypass (CPB) and survived at least to the first postoperative day. Ten of the 18 animals survived 7 days after surgery and were electively sacrificed. Animals with severe histopathological injury showed higher serum S-100beta protein levels at every time point after HCA. The strongest correlation between the total histopathologic score and serum S-100beta levels was found at 7 h after HCA (tau = 0.422 and p = 0.023). CONCLUSION: Serum S-100beta protein levels correlate with histopathological injury after a prolonged period of HCA in pigs. This finding supports the results of previous studies suggesting the potential accuracy of S-100beta in the prediction of brain injury after cardiac surgery.

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.

Myocardial metabolism and hemodynamics during coronary surgery without cardiopulmonary bypass.

BACKGROUND: Although renewed interest has recently been shown in coronary artery bypass grafting without cardiopulmonary bypass, no reports are available on myocardial metabolism and hemodynamics during temporary coronary occlusion and rotation of the contracting heart. METHODS: Changes in myocardial energy metabolism and hemodynamics were monitored in 12 patients undergoing elective coronary artery bypass grafting without cardiopulmonary bypass, and the postoperative efflux of creatine kinase-MB mass and troponin T were also determined. RESULTS: There was a significant increase in myocardial production of ATP degradation products (p = 0.026) and lactate (p = 0.004) during the operation. Myocardial oxygen extraction decreased (p = 0.012) in correlation with use of the short-acting beta-blocker, esmolol (r = -0.71). Apart from a decrease in mean arterial blood pressure (p = 0.002), there were no significant hemodynamic changes during the operation. The overall postoperative troponin T and creatine kinase-MB mass changes remained nonsignificant during the first two postoperative days. One patient had a myocardial infarction, diagnosed by electrocardiography, on the second postoperative day, but otherwise there were no major complications. CONCLUSIONS: Coronary artery bypass grafting without cardiopulmonary bypass seems to be well tolerated as only minor changes in myocardial energy metabolism and hemodynamics are observed during the operation.