Epsilon-aminocaproic acid improves postrecirculation hemodynamics by reducing intraliver activated protein C consumption in orthotopic liver transplantation.

BACKGROUND: Activated protein C (APC) is related to regulating the inflammatory response and hemodynamic stability upon reperfusion in cardiac operations and orthotopic liver transplantation (OLT). Epsilon-aminocaproic acid (EACA) is frequently used to treat fibrinolysis during OLT. It also has inhibitory effects related to the inflammatory response. However, it remains to be determined whether EACA can attenuate intraliver APC consumption and improve hemodynamic stability after reperfusion during OLT. METHODS: Fifty-nine recipients were randomized to receive either EACA (150 mg kg(-1) given intravenously prior to incision, followed by 15 mg kg(-1) h(-1) infusion until 2 h after the graft reperfusion) or the same volume of saline. Blood samples to assess plasma APC and protein C were obtained immediately before and after reperfusion from the inferior caval effluent or the portal veins for calculation of transliver differences (Δ). Hemodynamics and vasoactive medication use during the reperfusion period were observed in both groups. RESULTS: No transhepatic changes in protein C were found in either group. Immediately after reperfusion, a marked intraliver consumption of APC was noted in all recipients (P < 0.001), and intraliver consumption of APC in the control group was greater than that in the EACA-treated group (P < 0.05). Fewer requirements for vasoactive medication use after reperfusion and better initial graft function were noted in the EACA-treated group (P < 0.05). CONCLUSIONS: EACA can attenuate intraliver APC consumption and improve hemodynamic stability after reperfusion and initial graft function during OLT.

Homocysteine levels and cognitive function scores measured with MMSE and BCAT of middle-aged and elderly subjects in Tianjin City.

OBJECTIVE: China is proceeding into the aging society. There are near 6 million elderly suffering senile dementia,while cognitive impairment is an important clinical feature in dementia. The factors involved in cognitive dysfunction in the middle-aged and the elderly persons were investigated. DESIGN: Cross-sectional study. SETTING: Community dwellers and nursing home residents in Tianjin, China. SUBJECTS: Total of 662 subjects(284 men and 378 women) aged 55-93. METHODS: A designed questionnaire was used to collect their demographic data, information of disease and medication, and life style. Mini-mental state examination (MMSE) and Basic Cognitive Aptitude Tests (BCAT) software were applied to evaluate their cognitive function. Serum total homocysteine (tHcy) level was quantified by enzyme conversion method. A multiple linear stepwise regression analysis was applied to find the influencing factors of cognitive function. RESULTS: The average serum tHcy concentrations was 15.95±7.29 µmol/L, while the prevalence of hyperhomocysteinemia (HHE) was 45.4%. The average serum tHcy level and prevalence of HHE were higher in men than those in women after ruling out the age differences. The mean MMSE and BCAT scores were 26.74±2.71 and 50.26±18.84 respectively. The BCAT score was negatively correlated with age and positively correlated with education. Multiple linear stepwise regression equations showed that the P value was less than 0.001, the BCAT regression equation showed that the R2=0.453. Serum tHcy concentration was negatively correlated with total scores of BCAT, digit copy, Chinese character comparison, mental arithmetic, Chinese character rotation and recall answer of mental arithmetic test. Total scores of BCAT were negatively correlated with education, inhabitancy, serum tHcy concentration and age. In addition, Chinese character rotation was correlated with tea consumption. Remembrance and recognition of dual words and nonsense figures was correlated with income level. CONCLUSIONS: Hyperhomocysteinemia is associated with cognitive impairment in the middle-aged and the elderly persons in Tianjin. The BCAT scores could well represent the detailed cognitive function in elderly and negatively correlate with age, but positively correlated with education level. Serum tHcy concentration was negatively correlated with total BCAT scores.

Role of anhepatic time in endothelial-related coagulation in liver transplantation.

BACKGROUND: Disturbances in coagulation homeostasis are common in patients undergoing orthotopic liver transplantation (OLT) and anhepatic period is one of the important factors related to the coagulation abnormalities. The endothelium can regulate hemostasisby producing substances such as thrombomodulin (TM). The primary aim was to evaluate the effect of an hepatic time on the thrombomodulin-protein C system in patients undergoing OLT. METHODS: Fifty patients undergoing OLT were stratified in two groups: anhepatic time ≥ 60 min (N.=18) or anhepatic stage <60 min (N.=32). TM, protein C, activated protein C (APC) and (free) protein S plasma concentrations were measured by enzymelinked immunosorbent assays (ELISA) at the start of the surgery (To); immediately before the anhepatic period (A1); immediately before reperfusion (A2); 5 minutes; 15 minutes; 30 minutes after reperfusion of the graft (R1; R2; R3); at the end of operation (R4); the first day after operation (R5). RESULTS: Blood loss and transfusion were significantly greater in patients whose anhepatic time ≥ 60 min during the operation. TM levels increased most in patients whose anhepatic time ≥ 60 min. Protein C levels remained low throughout the surgery and decreased significantly at other points compared with To (P<0.05). There were no differences in protein C levels between groups except R5. The ratio of circulating APC activity to protein C antigen (APC/PC) increased significantly during the surgery. APC/PC ratio in the neohepatic stage increased significantly in patients whose anhepatic time ≥ 60 min (P<0.05). CONCLUSION: Patients with prolonged anhepatic time had greater changes in the thrombomodulin-protein C system.

Sevoflurane protects against acute kidney injury in a small-size liver transplantation model.

BACKGROUND: Living donor liver transplantation (LDLT) patients run the risk of developing acute kidney injury (AKI) and subsequent chronic kidney disease, affecting morbidity and mortality. Sevoflurane has anti-inflammation properties, and renal ischemia/reperfusion under sevoflurane anesthesia resulted in drastic improvements in renal function. Extrahepatic metabolism of sevoflurane has been reported in patients undergoing liver transplantation, and might lead to nephrotoxicity. However, whether sevoflurane anesthesia is safe with regard to renal function in small-size liver transplantation needs further investigation. As neutrophil gelatinase-associated lipocalin (NGAL) is an early predictive biomarker of AKI, we looked at the renal effects of sevoflurane in a rat liver transplantation model using small-for-size grafts to investigate the changes of NGAL level and kidney histology. METHODS: Sixty male Sprague-Dawley rats were randomly divided into 2 groups after 50% size liver transplantation. Rats were anesthetized with chloral hydrate or with sevoflurane and subjected to liver transplantation. Twelve rats in each group were used for the survival study and 6 rats were used for the hemodynamic study. Six rats in each group were sacrificed 2 or 24 h after reperfusion. We harvested kidneys and serum for further analysis, including histological and functional parameters; TNF-α, IL-6 and NGAL immunoassay; expressions of myeloperoxidase (MPO) activity; and NF-κB in renal tissues. RESULTS: Rats in the sevoflurane group had significantly lower Scr 24 h after reperfusion compared with those in the chloral hydrate group. Rats in the sevoflurane group demonstrated significantly reduced NGAL concentrations compared with rats in the chloral hydrate group 2 h after reperfusion. Epithelial necrosis in the chloral hydrate group (3.2 ± 0.8) was greater than that in the sevoflurane group (1.5 ± 1.1; p < 0.05). Sevoflurane anesthesia resulted in significantly lower plasma TNF-α and IL-6 concentrations and reduced MPO concentrations 2 h after reperfusion (p < 0.05). NF-κB protein levels 2 h after reperfusion increased by at least 110% in the chloral hydrate group relative to the sevoflurane group 2 h after reperfusion (p < 0.05). However, the urine inorganic fluoride concentrations increased significantly (p < 0.001) 2 h after reperfusion in the sevoflurane group (6.1 ± 1.5 µmol·l⁻¹) compared with the chloral hydrate group. CONCLUSIONS: Sevoflurane anesthesia can attenuate renal injury and modulate inflammatory cascades in small-size liver transplantation using rat models.

[Effect of Astragalan on secretion of tumor necrosis factors in human peripheral blood mononuclear cells].

The extracts of Astragalus membranaceus have been further isolated by liquid chromatography. One of the fractions (Astragalan, M.W. 20,000-25,000) could enhance the secretion of tumor necrosis factor (TNF) from human peripheral blood mononuclear cells (PBMC) in vitro. After isolation of adherent and nonadherent mononuclear cells from PBMC, Astragalan increased the secretion of TNF-alpha and TNF-beta respectively. These results suggest further study of Astragalan would promote the application of Astragalan in cancer immunotherapy.

Expression and pharmacological characterization of a stimulatory subtype of adenosine receptor in fetal chick ventricular myocytes.

Ventricular and atrial myocytes cultured from chick embryos 14 days in ovo were used as model systems to study cardiac adenosine receptors. In membranes of ventricular cultures, blocking of the A1-adenosine receptor pathway by the A1-selective antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) or by pertussis toxin treatment of the myocyte resulted in a significant adenosine agonist-mediated stimulation of the adenylate cyclase activity. The maximal increases in adenylate cyclase activity caused by the equipotent or the A2-adenosine receptor-selective agonists (from 52.1 +/- 3% to 63 +/- 10% [mean +/- SEM]) were significantly greater than those caused by the A1-selective agonists (from 11 +/- 5% to 34.6 +/- 7%) (p less than 0.01, by t test, n = 4-8). However, in membranes of atrial myocytes, when A1-subtype had been blocked, the various adenosine agonists had no effect on the adenylate cyclase activity. Whether the stimulatory adenylate cyclase-coupled adenosine receptor is also capable of stimulating contractility in the intact ventricular myocyte was next investigated. In ventricular but not in atrial cells, the various adenosine agonists caused an increase in the contractile amplitude in the presence of DPCPX or in myocytes preexposed to pertussis toxin. The increase in contraction amplitude caused by each agonist was expressed as percent of maximum (maximum is the increase in contractility caused by 2.4 mM calcium). In the pertussis toxin-treated myocyte, the maximal increases caused by the equipotent or A2-agonists (NECA, MECA, CV-1808, and CGS21680, from 49.6 +/- 3% to 52.5 +/- 6%, n = 8-12) were significantly greater than those elicited by the A1-agonists (2-CADO, S-PIA, R-PIA, and DCCA, from 12 +/- 4% to 37 +/- 3%, n = 8) (p less than 0.05, by t test). These data demonstrated that a stimulatory adenosine receptor, likely the A2-adenosine receptor, was present on the ventricular but not the atrial myocytes and was linked directly to a stimulation of the cardiac contractility. The functional effects mediated by the A1-subtype became manifested in the presence of isoproterenol, as evidence by an inhibition of the isoproterenol-stimulated increases in adenylate cyclase activity and in cardiac contractility by adenosine agonists. Thus, both subtypes of adenosine receptors, each mediating opposing responses, were present on the ventricular myocytes, whereas only the A1-subtype was found in the atria. The presence of a stimulatory functional A2-adenosine receptor may help explain the absence of a direct negative inotropic response to adenosine in the ventricle.