Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P17174 (aspartate aminotransferase)
 14,872 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cardiac metabolism following hypothermic potassium cardioplegia with blood as cardioplegia vehicle was studied in two groups of patients undergoing aortic valve replacement. In 15 patients, blood was given as single dose infusion (single dose group) and in 18 patients the same initial bolus was followed by a continuous perfusion (25-30 ml/min) with modified blood from the heart-lung machine (continuous blood group). Simultaneous samples were drawn from arterial and coronary sinus blood before and during the first 60 min after cardioplegia. In the continuous blood group, samples were also drawn during the period of cardioplegic perfusion. The samples were analyzed for PO 2, O2-saturation and content, PCO2, pH, lactate, pyruvate, glucose, potassium, myoglobin, creatine kinase (CK), its isoenzyme MB, and aspartate aminotransferase (ASAT). In addition myoglobin and enzymes were followed in peripheral venous blood for 24 hours. Myocardial biopsies were taken from the left ventricle at the beginning and end of cardioplegia and analyzed for adenosine triphosphate (ATP), creatine (C) and creatinephosphate (CP). The pattern of metabolic changes after cardioplegia was similar in both groups with decreased myocardial oxygen extraction, marked lactate and potassium release, increased glucose uptake and significant enzyme and myoglobin release. However, the degree of changes was significantly smaller in the continuous blood group. The myocardial biopsies also showed significantly less ATP and CP decrease in the continuous blood group, suggesting, together with the other metabolic results, that the myocardial protection afforded by continuous blood cardioplegia was superior to that of the single dose group. Furthermore, continuous perfusion permitted easy control of myocardial temperature during the period of aortic cross-clamping.
Scand J Thorac Cardiovasc Surg 1981
PMID:Myocardial protection during aortic valve replacement. Cardiac metabolism and enzyme release following continuous blood cardioplegia. 733 85

Cardiac metabolism following hypothermic potassium cardioplegia was studied in 23 patients undergoing isolated aortic valve replacement. All had normal coronary arteries. Cardioplegia was induced by infusing 700-1 000 ml of cold Ringer's acetate containing 20 mekv K+ selectively into the left coronary artery. Simultaneous blood samples were taken from the radial artery, a central vein and from the coronary sinus before and after cardioplegia. The PO2, O2-saturation and content, PCO2, pH, lactate, glucose, potassium, myoglobin, total creatine kinase (CK), its isoenzyme CK-MB, aspartate aminotransferase (ASAT) and alanine aminotransferase (ALAT) were assessed. Before bypass lactate was extracted by the heart. During the initial 10 to 20 min after cardioplegia there was a marked release of lactate in the coronary sinus. Myoglobin concentration and CK-MB serum activity peaked during the first 4 hours after the release of the aortic cross-clamping. In order to determine the best indicator of myocardial damage after cardioplegia, duration of extracorporeal circulation (ECC-time), aortic occlusion time (AOT), mean myocardial temperature (MMT) and the product of AOT and MMT, referred to as time-temperature area (TTA), were related to possible indicators of myocardial injury, such as enzyme and myoglobin release. The TTA was the best way of expressing the degree of exposure of the heart to ischaemia. The CK-MB to peak area (CK-MB max area) was the best indicator of the degree of ischaemic injury sustained by the heart during operation.
Scand J Thorac Cardiovasc Surg 1980
PMID:Myocardial protection during aortic valve replacement. Cardiac metabolism and enzyme release following hypothermic cardioplegia. 737 90

Three hundred and two consecutive patients who had undergone cardiac operation for various cardiac lesions were studied prospectively to evaluate the incidence, risk factors, and the associated mortality of postoperative hyperbilirubinemia after cardiopulmonary bypass. Concentrations of the serum total (conjugated and unconjugated) bilirubin, alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase, alkaline phosphatase, albumin, globulin, and serum haptoglobin were measured before the operation and again on the first, second, and seventh postoperative days. Postoperative hyperbilirubinemia was defined as occurrence of a serum total bilirubin concentration of more than 3 mg/dl in any measurement during the postoperative period. Logistic regression was done to identify possible risk factors for postoperative hyperbilirubinemia. Overall incidence of postoperative hyperbilirubinemia was 35.1%; the incidence of postoperative hyperbilirubinemia was higher in patients whose valves were replaced with mechanical prostheses than in those without prostheses (p < 0.00001). In patients with postoperative hyperbilirubinemia, 70% of the increase of total bilirubin on the first postoperative day came about from an increase in unconjugated bilirubin. Serum haptoglobin decreased significantly at the same time (p < 0.01). Development of the postoperative hyperbilirubinemia was associated with a higher mortality (5.6% versus 0.5%, p < 0.01) and higher frequency of use of intraaortic balloon counterpulsation, especially for patients in whom the highest postoperative total bilirubin occurred after the first 2 days. The numbers of valves replaced, preoperative right atrial pressure, and preoperative total bilirubin concentration are the significant risk factors that, in combination, correctly predict the occurrence of postoperative hyperbilirubinemia in 80% of the patients. We concluded that postoperative hyperbilirubinemia results mainly from an increase in unconjugated bilirubin and is associated with higher mortality, especially for patients in whom highest postoperative total bilirubin occurred late after operation. Patients with the higher preoperative right atrial pressure and total bilirubin level who then underwent multiple valve replacement procedures are at greater risk for development of postoperative hyperbilirubinemia.
J Thorac Cardiovasc Surg 1994 Sep
PMID:Hyperbilirubinemia after cardiac operation. Incidence, risk factors, and clinical significance. 766 5

Cardiopulmonary and other organ dysfunction often occurs after operation on the descending thoracic aorta. Though there are multiple causes of organ dysfunction in this setting, free radical injury may play a prominent role. Xanthine oxidoreductase, an enzyme that generates oxidants after exposure to ischemia, could be released from ischemic liver and intestine during reperfusion. To test this hypothesis, we created aortic occlusion in eight rabbits for 40 minutes by inflation of a 4F Fogarty balloon catheter in the descending thoracic aorta. Eight sham-operated rabbits served as a control group. Two hours of reperfusion followed removal of the balloon catheter. Hemodynamic and acid-base status were maintained near baseline values during reperfusion. Plasma samples were obtained for determination of the activity of the hepatocellular enzymes xanthine oxidoreductase, aspartate aminotransferase, alanine transferase, and lactate dehydrogenase. Plasma xanthine oxidoreductase activity increased significantly (p < 0.001) during reperfusion (729 +/- 140 microU/ml, mean +/- standard error of the mean) compared with baseline (132 +/- 18 microM/mL). The other enzymes followed a similar pattern of release. We report the release of xanthine oxidoreductase in an animal model that simulates the situation of human thoracic aorta operations. The oxidants produced by the circulating xanthine oxidoreductase observed during reperfusion would likely be toxic to vascular endothelium, potentially contributing to multiple organ dysfunction.
J Thorac Cardiovasc Surg 1994 May
PMID:Xanthine oxidoreductase release after descending thoracic aorta occlusion and reperfusion in rabbits. 817 64

University of Wisconsin (UW) solution was compared with modified St. Thomas cardioplegic solution for 6-hour preservation of isolated working rat hearts. The hearts (9 in each group) were arrested with the respective solution and stored, still cannulated, for 6 hours at 4 degrees C. After retrograde reperfusion for 30 minutes, antegrade perfusion was begun at constant left atrial and aortic pressures. Following 25 minutes of antegrade perfusion the hemodynamic recovery of the UW-preserved hearts was superior to that of the other hearts (cardiac output 46.0 +/- 4.8% of the preischemic control values in the UW group and 10.0 +/- 6.0% in the St. Thomas group, p < 0.01). The adenosine triphosphate content was significantly higher in the UW-preserved hearts (18.8 +/- 0.9 vs. 14.7 +/- 1.6 mumol/g dry weight, p < 0.05). No significant intergroup difference was found in aspartate aminotransferase leak or tissue glycogen. The study demonstrated both better function and enhancement of high-energy phosphates with UW solution vs. modified St. Thomas solution in isolated rat hearts, although without difference in enzyme leakage or tissue glycogen, after 6-hour preservation.
Scand J Thorac Cardiovasc Surg 1993
PMID:Six-hour preservation of the isolated working rat heart improved with University of Wisconsin solution. 849 91

We determined whether the paracrine liver endothelin (ET) system participates in the pathogenesis of CCl4-induced hepatotoxicity. Wistar-Kyoto rats were divided into four groups: a bosentan-treated group with CCl4 intoxication, a vehicle-treated group with CCl4 intoxication, a nontreated control group, and a bosentan-treated control group. Hepatotoxicity was assessed by determination of serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and lactate dehydrogenase (LDH). Tissue ET-1 concentrations and expression of endothelin receptor subtypes were analyzed. The liver tissue levels of ET-1 in rats with CCl4 intoxication were significantly higher than in normal rats. Scatchard analysis revealed no differences in the density and binding constants of ETA and ETB receptors between rats with CCl4 intoxication and controls. Bosentan treatment of rats undergoing CCl4 inhalation resulted in significant protection against elevation of ALT, AST, LDH, and bilirubin. In conclusion, this study showed that the paracrine ET system in involved in the pathogenesis of CCl4-induced hepatotoxicity and that blockade of the stimulated liver endothelin system reduces CCl4-induced liver injury.
J Cardiovasc Pharmacol 1995
PMID:Protective effects of the mixed endothelin receptor antagonist bosentan in rats with CCL4-induced liver injury. 858 41

Microdialysis probes permeable to large molecules (m.w. cut-off > 200 kD) were introduced into the myocardium of anaesthetized pigs in order to evaluate their potential for early detection of myocardial ischaemia and enzyme markers for infarction. The left anterior descending coronary artery was occluded for 30 min and the myocardium was reperfused for 3 h. The concentrations of aspartate aminotransferase (ASAT), lactate, glucose and selected free amino acids were measured. The levels in the interstitium of ischaemic and non-ischaemic myocardium were compared with those in plasma from the coronary sinus as well as from a peripheral vein. Twelve probes were inserted in six pigs and withdrawn after 8-72 hours of sampling. No complications occurred. Simultaneous 100% increase of ASAT and lactate was found in myocardial dialysates after 30 min of ischaemia. ASAT activity remained at that level until the end of reperfusion. The plasma peak ASAT level was not attained until after 3 h. Glutamate was the only amino acid which increased significantly in the myocardial interstitium during ischaemia, peaking after 30 min of reperfusion. Dialysates from the unaffected myocardium showed no effects on lactate, ASAT or glutamate. The use of myocardial microdialysis for pre- and postoperative recordings in man is discussed.
Scand Cardiovasc J 1997
PMID:In situ detection of myocardial infarction in pig by measurements of aspartate aminotransferase (ASAT) activity in the interstitial fluid. 945 83

BACKGROUND: The metabolic and hemodynamic effects of nisoldipine supplementation in cardioplegia after ischemic injury were investigated in 13 isolated rabbit hearts. Group 1 consisted of 6 hearts, which received St. Thomas II cardioplegic solution. In group 2, nisoldipine was added to the cardioplegic solution at a concentration of 0.1 mg/kg in 7 hearts. METHODS: The explanted hearts were suspended from Langendorff apparatus and were perfused with Krebs-Henseleit solution. Left ventricular pressure, heart rate, malondialdehyde, glutathione peroxidase, glutathione reductase, reduced glutathione, oxidized glutathione, creatine kinase MB, (CK-MB), aspartate transaminase, and lactate dehydrogenase (LDH) were measured before and after 60 minutes of ischemia. Peak generated pressure after ischemia was significantly higher in group 2 versus group 1 while end-diastolic pressure was significantly lower in group 2 after ischemic arrest (P <.05). RESULTS: Malondialdehyde levels were lower in group 2 (P <.05). Glutathione peroxidase and glutathione reductase levels were significantly higher in group 2 (P <.05). The only enzymatic significant difference was observed between the preischemic and postischemic levels of aspartate transaminase in group 2 (P <.05). CONCLUSIONS: These findings show beneficial effects of nisoldipine cardioplegia, although its use as a cardioplegic additive is not yet possible. We believe, however, the effects of oral nisoldipine before cardiac surgery can be studied in a clinical setting.
J Cardiovasc Pharmacol Ther 1997 Oct
PMID:Nisoldipine Cardioplegia in the Isolated Rabbit Heart. 1068 69

During ischemia-reperfusion an imbalance between endothelin (ET) and nitric oxide (NO) can be responsible for microcirculatory disturbances. The aim of this study was to restore the ET/NO balance to reduce the ischemia-reperfusion injury. Hepatic ischemia was induced for 30 min in 56 Wistar rats. Sham operation, ischemia and treatment groups with the ET receptor antagonist (ERA) bosentan (1 mg/kg body weight i.v.) and the NO donor L-arginine (400 mg/kg body weight i.v.) were performed. For evaluation of hepatic microcirculation in vivo microscopy was carried out 30-90 min after reperfusion. Local hepatic tissue PO2, laser Doppler flow and aspartate aminotransferase/alanine aminotransferase (AST/ALT) levels were measured. Increased ET caused sinusoidal constriction after reperfusion to 76% of the sham group (p < 0.05), leading to significant decrease in perfusion rate (82%), liver tissue PO2 (6.9 mmHg) and erythrocyte flux (45.2% of sham group). Hepatocellular damage could be detected 6 h after reperfusion by AST/ALT increase (p < 0.05). Sinusoidal diameters were maintained at baseline in the ERA (98%) and NO (102%) groups (p < 0.05). Increased percentage of leukocytes sticking in sinusoids (144%) and venules (435%) was reduced by therapy to 110/253% (ERA) and 111/324% (NO), respectively (p < 0.05). Perfusion rate was increased to 93 and 94% (p < 0.05 vs ischemia). Local hepatic tissue PO2 was improved 30 min after reperfusion in the ERA (11.0 mmHg) as well as in the NO group (11.5 mmHg; p < 0.05 vs ischemia). Measurement with a laser Doppler flow meter revealed significant improved erythrocyte flux in both therapy groups (p < 0.05 vs ischemia). Also, the post-ischemic AST/ALT increase was reduced by therapy. In conclusion, ET evokes strong constriction of post-ischemic sinusoids, leading to microcirculatory disturbances. The maintenance of the ET/NO balance by blocking ET receptors, or providing an NO donor, protects liver microcirculation and reduces hepatic ischemia-reperfusion injury.
J Cardiovasc Pharmacol 2000 Nov
PMID:Endothelin/nitric oxide balance influences hepatic ischemia-reperfusion injury. 1107 80

Ischemia leads to profound endothelin- (ET) related constriction of hepatic microvessels, causing disturbances in blood and oxygen supply. The aim of the study was to modulate hepatic microvascular diameters by blocking ET receptors to find the optimal therapeutic vessel width for reduction of ischemia-reperfusion injury. In an in vivo model (84 female Wistar rats, 250-300 g) with portal decompression by means of a splenocaval shunt, normothermic hepatic ischemia was induced for 30 min by crossclamping of the hepatoduodenal ligament. The ET receptor antagonist (ERA) bosentan was administered before induction of ischemia in different dosages [0.1, 1.0 and 10.0 mg/kg body weight (BW) i.v. and 10 mg/kg BW intraportally (i.p.)]. The effect on microcirculation was assessed by in vivo microscopy and influence on hepatocellular function by measurement of aspartate aminotransferase (AST) levels. Sinusoidal diameters were reduced as a result of ischemia to 76.3 +/- 7.4% compared with values received from sham-operated animals. After application of 0.1 mg/kg of bosentan, sinusoids remained constricted (89.7 +/- 9.9%, AST 255.0 +/- 12.8 U/l). Blocking ET receptors with 1 mg/kg bosentan avoided sinusoidal constriction (99.0 +/- 8.8%, p < 0.05) and led to the most effective reduction of AST level peak after 6 h of reperfusion (244.0 +/- 34.2 U/l vs 422.9 +/- 163.3 U/l in untreated ischemia). Bosentan (10 mg/kg i.v.) caused an increase in sinusoidal diameter to 109.1 +/- 6.4% (AST 311.7 +/- 33.6 U/l) and 10 mg/kg i.p. to 136.8 +/- 19.3% and even increase AST levels (618.90 +/- 209.32 U/l). After intravenous application of 1 and 10 mg/kg BW bosentan the perfusion rate was significantly increased and sticking of leukocytes in sinusoids and venules reduced (p < 0.05). In our model, diameters of sinusoids and postsinusoidal venules could be regulated gradually. We conclude that the avoidance of constriction, but not an excessive vasodilation leads to increased perfusion rate and hence improved hepatocellular function.
J Cardiovasc Pharmacol 2000 Nov
PMID:Endothelin receptor blockade as a therapeutic strategy in ameliorating postischemic damage to the liver microcirculation. 1107 18


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