Blockade of P-Glycoprotein Decreased the Disposition of Phenformin and Increased Plasma Lactate Level

This study aimed to investigate the in vivo relevance of P-glycoprotein (P-gp) in the pharmacokinetics and adverse effect of phenformin. To investigate the involvement of P-gp in the transport of phenformin, a bi-directional transport of phenformin was carried out in LLC-PK1 cells overexpressing P-gp, LLC-PK1-Pgp. Basal to apical transport of phenformin was 3.9-fold greater than apical to basal transport and became saturated with increasing phenformin concentration (2-75 µM) in LLC-PK1-Pgp, suggesting the involvement of P-gp in phenformin transport. Intrinsic clearance mediated by P-gp was 1.9 µL/min while passive diffusion clearance was 0.31 µL/min. Thus, P-gp contributed more to phenformin transport than passive diffusion. To investigate the contribution of P-gp on the pharmacokinetics and adverse effect of phenformin, the effects of verapamil, a P-gp inhibitor, on the pharmacokinetics of phenformin were also examined in rats. The plasma concentrations of phenformin were increased following oral administration of phenformin and intravenous verapamil infusion compared with those administerd phenformin alone. Pharmacokinetic parameters such as Cmax and AUC of phenformin increased and CL/F and Vss/F decreased as a consequence of verapamil treatment. These results suggested that P-gp blockade by verapamil may decrease the phenformin disposition and increase plasma phenformin concentrations. P-gp inhibition by verapamil treatment also increased plasma lactate concentration, which is a crucial adverse event of phenformin. In conclusion, P-gp may play an important role in phenformin transport process and, therefore, contribute to the modulation of pharmacokinetics of phenformin and onset of plasma lactate level.

Plasma Lactate and Base Deficit: Early Predictors of Morbidity in Burn Patients

PURPOSE: Plasma lactate and base deficit has been used as a marker to determine the status of tissue perfusion in trauma and clinically ill patients and also to predict the outcome of these patients. This study was performed to investigate the effect of plasma lactate and base deficit in predicting burn patients outcome. METHODS: A retrospective review was performed on 102 patients from January 2012 to December 2013 who were admitted as severe burn patients to our burn care unit. Plasma lactate and base deficit were measured upon admission to the hospital and SIRS score, hospital day, ABSI and TBSA were collected after admission. RESULTS: 102 patients were enrolled. Initial base deficit, hospital day, burn surface area and ABSI score showed statistical differences between low SIRS group and high SIRS group. The SIRS score, hospital day and ABSI score showed statistical differences between high base deficit group and low base deficit group (P0.05). CONCLUSION: In this study, initial base deficit but not plasma lactate, was predictor of morbidity following burn injury.

Serum Lactate and Base Deficit: Early Predictors of Morbidity and Mortality in Burn Patients with Inhalation Injury

PURPOSE: The aim of this study was to elucidate whether plasma lactate (PL) and base deficit (BD) are useful early parameters to predict the prognosis of burn patients with inhalation injury. In addition, one of the main objectives was to evaluate if PL and its change, BD and its change due to fluid resuscitation, adds additional information. METHODS: A retrospective review was performed on 151 patients admitted to our burn intensive care unit who were suspected to have inhalation burn injury, and then were confirmed by fibreoptic bronchoscopy between 1 Jan 2008 and 31 Dec 2008. All patients received proper fluid and electrolyte resuscitation, pain management, nutritional support, wound care and surgical debridement of dead tissue by burn surgeon. RESULTS: Initial PL, PL1 (24 hours later) and initial BD show statistical differences between survivors group and non-survivors group. A better chance of survival occurs when resuscitation results in normal PL values within 24 h. Moreover, an outcome predictor of shock and effective resuscitation could be defined by evaluating the changes of BD on Day 1. Normalization of the BD within 24 h is associated with a better chance of survival. CONCLUSION: Measuring PL, BD and their changes may help to identify burn patients either for adequacy of treatment, or selection of other therapeutic options. Therefore titration of burn resuscitation to normalize PL and BD levels may be a reasonable method to improve burn mortality.

Effect of increases in plasma lactate concentration on intravascular hemolysis during exhaustive exercise / 体力科学

A study was performed to examine the effect of plasma lactate concentration on intravascular hemolysis during exercise. Seven men performed maximal and submaximal exercise on a cycle ergometer. The maximal exercise was performed as a graded exercise until exhaustion. The mean performance time of the maximal exercise was 15 min and 4 s. The submaximal exercise was performed for 30 min at 50% HRmax. Blood samples were obtained before, immediately after, and one hour after exercise. Plasma lactate concentration, hematocrit (Ht), and serum haptoglobin concentration (Hp) were measured. Hp was corrected by Ht for hemoconcentration and expressed as HpC. Plasma lactate concentration was elevated significantly (p<0.05) immediately after maximal exercise, and returned to the baseline values one hour after exercise, whereas plasma lactate concentration did not change after submaximal exercise. Hp and HpC did not change even after maximal exercise. These results suggest that the elevation in plasma lactate concentration may not affect intravascular hemolysis during exercise.

Energy systems during the last spurt (exertion) in an 800-m race / 体力科学

A study was conducted to investigate the relationship between energy systems and running performance, especially during the last spurt in an 800-m race. The subjects were separated into good 800-m runners (group A n=5: best record, 1′54″3±1.4) and a second group of slower 800-m runners (group B n=4: best record, 2′02″1±1.3) . Each group executed two types of running test (600m test and 800m test) . To simulate an 800-m race, the running speed up to 600m was set by means of a lamp pace maker system. The last spurt was running 200m at maximal voluntary running speed. Plasma lactate, plasma ammonia, serum glucose and blood pH were assayed at rest, after warming up, and 6 and 10min after the running test.<BR>The following results were obtained:<BR>1) The last spurt time of group A was significantly faster than that of group B (p<0.01) . 2) In group A, plasma lactate and plasma ammonia concentrations increased significantly during the last spurt (p<0.05) . In group B, however, plasma lactate and plasma ammonia concentrations before the last spurt (600m test values) were very close to the values after the last spurt (800m test values), 3) Last spurt times were significantly related to changes in plasma lactate concentration (r=-0.870, p<0.01) and O<SUP>2</SUP> debt (r=-0.799, p<0.01) during the last spurt.<BR>These results suggest that running performance during the last spurt in an 800-m race depends on anaerobic energy ability, as reflected by plasma lactate, plasma ammonia and O<SUP>2</SUP> debt before the last spurt.