Circulatory arrest and low-flow cardiopulmonary bypass alter CREB phosphorylation in piglet brain.
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BACKGROUND: The purpose of this study was to determine the effects of low-flow cardiopulmonary bypass (CPB) and deep hypothermic circulatory arrest followed by postbypass recovery on the phosphorylation state of transcription factor, cyclic adenosine 3', 5'-monophosphate response element-binding protein (CREB), in the striatum of neonatal brain. METHODS: Neonatal piglets (1.4 to 2.5 kg) anesthetized with isoflurane and fentanyl were put on CPB. The animals were cooled to 18 degrees C during a 20-minute period. The CPB circuit flow was then either reduced to 20 mL.kg(-1).min(-1) for 90 minutes (low-flow CPB) or turned off for 90 minutes (deep hypothermic circulatory arrest), following with a gradual increase in the flow and rewarming during a 30-minute period and a 2-hour recovery. At the end of the recovery period, the animals were rapidly euthanized, and the striata were removed and frozen for immunochemical analysis by Western blot technique using antibodies against phosphorylated and total CREB. The results are presented as mean +/- standard deviation (p < 0.05 was significant). RESULTS: Deep hypothermic circulatory arrest did not result in alteration in either the level of CREB or its degree of phosphorylation in the piglet striatum whereas after low-flow CPB, CREB phosphorylation was significantly increased (p < 0.005) and there was also an increase in CREB expression (p < 0.01). CONCLUSIONS: This study indicates that at 2 hours of recovery, low-flow CPB but not deep hypothermic circulatory arrest causes an increase in CREB phosphorylation and expression. Future studies will determine the degree to which the increase in CREB phosphorylation correlates with cell survival and neuronal injury after CPB. (+info)
Effects of cold cardioplegia on pH, Na, and Ca in newborn rabbit hearts.
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Many studies suggest myocardial ischemia-reperfusion (I/R) injury results largely from cytosolic proton (H(i))-stimulated increases in cytosolic Na (Na(i)), which cause Na/Ca exchange-mediated increases in cytosolic Ca concentration ([Ca]i). Because cold, crystalloid cardioplegia (CCC) limits [H]i, we tested the hypothesis that in newborn hearts, CCC diminishes H(i), Na(i), and Ca(i) accumulation during I/R to limit injury. NMR measured intracellular pH (pH(i)), Na(i), [Ca]i, and ATP in isolated Langendorff-perfused newborn rabbit hearts. The control ischemia protocol was 30 min for baseline perfusion, 40 min for global ischemia, and 40 min for reperfusion, all at 37 degrees C. CCC protocols were the same, except that ice-cold CCC was infused for 5 min before ischemia and heart temperature was lowered to 12 degrees C during ischemia. Normal potassium CCC solution (NKCCC) was identical to the control perfusate, except for temperature; the high potassium (HKCCC) was identical to NKCCC, except that an additional 11 mmol/l KCl was substituted isosmotically for NaCl. NKCCC and HKCCC were not significantly different for any measurement. The following were different (P < 0.05). End-ischemia pH(i) was higher in the CCC than in the control group. Similarly, CCC limited increases in Na(i) during I/R. End-ischemia Na(i) values (in meq/kg dry wt) were 115 +/- 16 in the control group, 49 +/- 13 in the NKCCC group, and 37 +/- 12 in the HKCCC group. CCC also improved [Ca]i recovery during reperfusion. After 40 min of reperfusion, [Ca](i) values (in nmol/l) were 302 +/- 50 in the control group, 145 +/- 13 in the NKCCC group, and 182 +/- 19 in the HKCCC group. CCC limited ATP depletion during ischemia and improved recovery of ATP and left ventricular developed pressure and decreased creatine kinase release during reperfusion. Surprisingly, CCC did not significantly limit [Ca]i during ischemia. The latter is explained as the result of Ca release from intracellular buffers on cooling. (+info)
Increasing duration of deep hypothermic circulatory arrest is associated with an increased incidence of postoperative electroencephalographic seizures.
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OBJECTIVE: Electroencephalographic seizures have been shown to occur in 5% to 20% of neonates and infants after biventricular repair of a variety of cardiac defects. Occurrence of a seizure is a predictor of adverse long-term neurodevelopmental sequelae. The contemporary incidence of postoperative seizures after repair of cardiac defects such as hypoplastic left heart syndrome and other forms of single ventricle is not known. METHODS: A prospective study of 178 patients less than 6 months of age undergoing cardiopulmonary bypass with or without deep hypothermic circulatory arrest (DHCA) was conducted at a single institution from September 2001 through March 2003 to identify postoperative seizures assessed by 48-hour continuous video electroencephalographic monitoring. RESULTS: Cardiac defects included transposition of the great arteries with or without a ventricular septal defect (n = 12), ventricular septal defect with or without coarctation (n = 28), tetralogy of Fallot (n = 24), hypoplastic left heart syndrome or variant (n = 60), other functional single ventricle (n = 14), and other defects suitable for biventricular repair (n = 40). Median age at the time of the operation was 7 days (range, 1-188 days) and was 30 days or less in 110 (62%) patients. DHCA was used in 117 (66%) patients, with multiple episodes in 9 patients. Median total duration of DHCA was 40 minutes (range, 1-90 minutes). Electroencephalographic seizures were identified in 20 (11.2%) patients. Seizures occurred in 15 (14%) of 110 neonates and 5 (7%) of 68 older infants. Seizures occurred in 1 (4%) of 24 patients with tetralogy of Fallot, 1 (8%) of 12 with transposition of the great arteries, and 11 (18%) of 60 with hypoplastic left heart syndrome or variant. By stepwise logistic regression analysis, once increasing duration of total DHCA (P = .001) was considered, no other variable improved prediction of occurrence of a seizure. Patients with DHCA duration of more than 40 minutes had an increased incidence of seizures (14/58 [24.1%]) compared with those with a DHCA duration of 40 minutes or less (4/59 [6.8%], P = .04). The incidence of seizures for patients with a DHCA duration of 40 minutes or less was not significantly different from those in whom DHCA was not used (2/61 [3.3%], P = .38). CONCLUSIONS: In the current era, continuous electroencephalographic monitoring demonstrates early postoperative seizures in 11.2% of a heterogeneous cohort of neonates and infants with complex congenital heart defects. Increasing duration of DHCA was identified as a predictor of seizures. However, the incidence of seizures in children with limited duration of DHCA was similar to that in infants undergoing continuous cardiopulmonary bypass alone. (+info)
Brain oxygen and metabolism during circulatory arrest with intermittent brief periods of low-flow cardiopulmonary bypass in newborn piglets.
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OBJECTIVE: We performed this study to determine whether brief intermittent periods of low-flow cardiopulmonary bypass during deep hypothermic circulatory arrest would improve cortical metabolic status and prolong the "safe" time of deep hypothermic circulatory arrest. METHODS: After a 2-hour baseline, newborn piglets were placed on cardiopulmonary bypass and cooled to 18 degrees C. The animals were then subjected to 80 minutes of deep hypothermic circulatory arrest interrupted by 5-minute periods of low-flow cardiopulmonary bypass at either 20 mL x kg(-1) x min(-1) (LF-20) or 80 mL x kg(-1) x min(-1) (LF-80) during 20, 40, 60, and 80 minutes of deep hypothermic circulatory arrest. All animals were rewarmed, separated from cardiopulmonary bypass, and maintained for 2 hours (recovery). The oxygen pressure in the cerebral cortex was measured by the quenching of phosphorescence. The extracellular dopamine level in the striatum was determined by microdialysis. Results are means +/- SD. RESULTS: Prebypass oxygen pressure in the cerebral cortex was 65 +/- 7 mm Hg. During the first 20 minutes of deep hypothermic circulatory arrest, cortical oxygen pressure decreased to 1.3 +/- 0.4 mm Hg. Four successive intermittent periods of LF-20 increased cortical oxygen pressure to 6.9 +/- 1.2 mm Hg, 6.6 +/- 1.9 mm Hg, 5.3 +/- 1.6 mm Hg, and 3.1 +/- 1.2 mm Hg. During the intermittent periods of LF-80, cortical oxygen pressure increased to 21.1 +/- 5.3 mm Hg, 20.6 +/- 3.7 mm Hg, 19.5 +/- 3.95 mm Hg, and 20.8 +/- 5.5 mm Hg. A significant increase in extracellular dopamine occurred after 45 minutes of deep hypothermic circulatory arrest alone, whereas in the groups of LF-20 and LF-80, the increase in dopamine did not occur until 52.5 and 60 minutes of deep hypothermic circulatory arrest, respectively. CONCLUSIONS: The protective effect of intermittent periods of low-flow cardiopulmonary bypass during deep hypothermic circulatory arrest is dependent on the flow rate. We observed that a flow rate of 80 mL x kg(-1) x min(-1) improved brain oxygenation and prevented an increase in extracellular dopamine release. (+info)
Management of air embolism during HeartMate XVE exchange.
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Air embolism is a rare and usually fatal complication of major cardiac surgery. We present a case in which a 45-year-old man supported by a HeartMate(R) XVE left ventricular assist device required a pump exchange due to failure of the device motor. During pump dissection, a massive amount of air entered the systemic circulation. Urgent cannulation for cardiopulmonary bypass was performed, and cardiopulmonary bypass was initiated, followed by profound hypothermia, circulatory arrest, retrograde cerebral perfusion, retrograde coronary sinus perfusion, and then barbiturate coma and steroid therapy. The HeartMate XVE left ventricular assist device was removed, and a HeartMate II was implanted. After 5 days, the patient awoke with left hemiparesis, which nearly resolved with aggressive physical therapy. Forty-four days after the pump exchange operation, the patient was discharged from the hospital with only mild left hemiparesis. Exposure of the left ventricular assist device or its external components requires careful monitoring, because air can enter the pump-particularly in a hypovolemic patient. Rapid response after massive air entry into the left ventricular assist device system, as in our patient, can result in a successful outcome. (+info)
Response of brain oxygenation and metabolism to deep hypothermic circulatory arrest in newborn piglets: comparison of pH-stat and alpha-stat strategies.
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BACKGROUND: To determine the effect of pH-stat as compared with alpha-stat management on brain oxygenation, level of striatal extracellular dopamine, phosphorylation, and levels of protein kinase B (Akt) and cyclic adenosine 3', 5'-monophosphate response element-binding protein (CREB), and levels of extracellular signal-regulated kinase (ERK)1/2, Bcl-2, and Bax in a piglet model of deep hypothermic circulatory arrest (DHCA). METHODS: The piglets were placed on cardiopulmonary bypass (CPB), cooled with pH-stat or alpha-stat to 18 degrees C, subjected to 90 minutes of DHCA, rewarmed, weaned from CPB, and maintained for two hours recovery. The cortical oxygen was measured by: quenching of phosphorescence; dopamine by microdialysis; phosphorylation of CREB (p-CREB), ERK (p-ERK) 1/2, Akt (p-Akt), and level of Bcl-2, Bax by Western blots. RESULTS: Oxygen pressure histograms for the microvasculature of the cortex show substantially higher oxygen levels during cooling and during the oxygen depletion period after cardiac arrest (up to 15 minutes) when using pH-stat compared with alpha-stat management. Significant increases in dopamine occurred at 45 minutes and 60 minutes of DHCA in the alpha-stat and pH-stat groups, respectively. The p-CREB and p-Akt in the pH-stat group were significantly higher than in the alpha-stat group (140 +/- 9%, p < 0.05 and 125 +/- 6%, p < 0.05, respectively). There was no significant difference in p-ERK1/2 and Bax. The Bcl-2 increased in the pH-stat group to 121 +/- 4% (p < 0.05) compared with the alpha-stat group. The ratio Bcl-2:Bax increased in the pH-stat group compared with the alpha-stat group. CONCLUSIONS: The increase in p-CREB, p-Akt, Bcl-2, Bcl-2/Bax, and delay in increase of dopamine indicated that pH-stat, in the piglet model, prolongs "safe" time of DHCA and provides some brain protection against ischemic injury. (+info)
Giant size abdominal aortic aneurysm repair using open proximal anastomosis under hypothermic circulatory arrest: a report of two cases.
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Hypothermic total circulatory arrest and open proximal anastomosis techniques are not commonly used in abdominal or juxtarenal abdominal aortic aneurysm repair. Proximal aortic clamping is usually adequate for surgical repair of abdominal aortic pathologies. We present two cases of giant-sized abdominal aortic aneurysms, one was juxtarenal and one was a Crawford type IV thoracoabdominal aneurysm, that were repaired by using open proximal anastomosis under hypothermic total circulatory arrest and a transabdominal approach. This technique may be useful for both thoracoabdominal and large abdominal aortic aneurysms because it offers the opportunity to not clamp the aorta and operate in bloodless surgical field. (+info)
Hybrid antegrade repair of the arch and descending thoracic aorta with a new integrated stent-Dacron graft in acute type A aortic dissection: a look into the future with new devices.
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A young male patient underwent supracoronary replacement of the ascending aorta for acute type A dissection under hypothermic circulatory arrest. After discharge, he was readmitted two weeks later due to severe aortic regurgitation and acute arch redissection. Under a second period of hypothermic circulatory arrest three weeks after the initial operation, radical treatment with aortic valve replacement, replacement of the ascending aorta and arch, together with antegrade deployment of a stent-graft in the true lumen for frozen elephant-trunk technique, were successfully performed. Computed tomography at four weeks showed complete proximal repair and thrombosis of the false lumen. Transesophageal echocardiography at eight weeks confirmed repair. The patient is currently leading an active life. A hybrid approach for complex cases of acute type A dissection with arch involvement can be considered for the future. (+info)