Pharmacokinetics and interaction pharmacodynamics of dexmedetomidine in humans

Dexmedetomidine is a potent and highly selective α₂-adrenoceptor agonist with a selectivity ratio of 1600:1 (α₂:α₁). Dexmedetomidine is a highly lipophylic agent that is rapidly distributed to tissues with a distribution half-life (t_1/2α) of approximately 6 minutes. It is extensively distributed and rapidly eliminated, with a mean elimination half-life (t_1/2) of 2–2.5 hours. This rapid distribution and short elimination kinetics makes dexmedetomidine amenable to frequent titration allowing adjustability of dosage and effects. Generally, dexmedetomidine does not exhibit pharmacokinetic-based interactions; however, dosage modifications of some concomitant medications may be needed to be adjusted due primarily to common pharmacological actions of the two drugs. Dexmedetomidine is eliminated by metabolism to inactive metabolites, primarily glucuronides. Eighty to ninety percent of an administered dose is excreted in the urine and 5%–13% in the faeces.     

Isoflurane alters the amount of dopamine transporter expressed on the plasma membrane in humans

BACKGROUND: Isoflurane increases extracellular dopamine concentration and causes trafficking of the dopamine transporter (DAT) in transfected cells. Also, the binding potentials of highly specific positron-emitting DAT ligands are altered by isoflurane in rhesus monkeys. The purpose of this study was to determine the dose-response curve for isoflurane altering the binding potential of one of these ligands ([F-18]FECNT) in humans. METHODS: Twenty human volunteers underwent positron emission tomography using [F-18]FECNT. All subjects were scanned while awake and then again after assignment to one of four groups (n = 5 each): awake-control, propofol-control, or light or deep isoflurane anesthesia as defined by Bispectral Index monitoring. Bispectral Index values in the light anesthesia group were 40 +/- 7 (end-tidal isoflurane, 1.02 +/- 0.08) versus 27 +/- 10 (end-tidal isoflurane, 1.6 +/- 0.3) in the deep anesthesia group. The within-subject percent change in putamen binding potential between the awake and second scans was determined for each subject, averaged within groups, and compared across groups. RESULTS: The [F-18]FECNT binding potential exhibited a biphasic shape as a function of anesthetic dose. The binding potential for the second scan in the awake-control and propofol-control groups was significantly less than the initial scan; for the light anesthesia group, the binding potential was significantly increased during anesthesia, and no change was detected between the two scans in the deeper anesthesia group. CONCLUSION: Isoflurane causes a dose-dependent change in the [F-18]FECNT binding potential for DAT consistent with isoflurane causing trafficking of the DAT between the plasma membrane and the cell interior. Concentrations of isoflurane below minimum alveolar concentration causes DAT to be trafficked to the plasma membrane from the cell interior, but no net trafficking occurs at higher concentrations. The data are most easily explained if isoflurane alters the amount of functionally expressed DAT through an indirect pathway. This phenomena should be more fully explored to help make the next generation of anesthetics more mechanistically specific and to reduce undesired side effects.     

异丙酚对多巴胺转运蛋白转运功能的影响

目的 研究异丙酚对多巴胺转运蛋白(DAT)转运功能的影响。方法 ①应用高表达DAT的中华仓鼠卵巢(CHO)细胞,在给予异丙酚后,测定 DAT摄取氢~3H标记的多巴胺(~3H-DA)功能;②应用非线性动力学方法,观测异丙酚作用时,DAT最大摄取速度(Vmax)和米氏常数(Km)的变化。结果 异丙酚显著降低了高表达多巴胺转运蛋白的中华仓鼠卵巢(CHO/DAT)细胞对多巴胺(DA)的摄取能力;异丙酚药物转运动力学实验表明,异丙酚降低了CHO/DAT对~H-DA的Vmax,对照细胞和异丙酚用药细胞Vmax分别为16.67pmol·min~(-1)·10~(-5)cells和11.6pmol·min~(-1)·10~(-5)cells,但与DAT的亲和力未发生改变,Km分别为0.46pmol·L~(-1)和0.53pmol·L~(-1)。结论 异丙酚以非竞争性的方式抑制了DAT的转运功能,降低了多巴胺(DA)的再摄取,导致突触间隙DA浓度升高,从而增强了中枢多巴胺能神经信息的传递。     

Effect of acute hyperglycemia on insulin secretion in humans

First-phase insulin response to intravenous glucose is impaired both in type 2 diabetic patients and in subjects at risk for the disease. Hyperglycemia can modify beta-cell response by either inhibiting or potentiating both first- and second-phase insulin release. In normal subjects, the effect of acute hyperglycemia on insulin secretion is controversial. We measured (in 13 healthy volunteers) insulin secretion (by deconvolution of plasma C-peptide concentrations) during three consecutive 30-min hyperglycemic steps (2.8, 2.8, and 5.6 mmol/l), followed by an intravenous arginine bolus. First-phase insulin secretion in response to the first hyperglycemic step (456 +/- 83 pmol.min(-1).m(-2)) was significantly larger than that in response to the second step (311 +/- 37 pmol.min(-1).m(-2), P < 0.01); the subsequent increase in glycemia failed to stimulate first-phase secretion any further (377 +/- 60 pmol.min(-1).m(-2), NS vs. the previous value). This inhibition was also evident when insulin release rates were corrected for the respective increments (absolute or percentage) in plasma glucose levels and was not due to beta-cell exhaustion because the arginine bolus still elicited a large peak of insulin secretion (4,790 +/- 2,330 pmol.min(-1).m(-2)). In contrast, second-phase insulin secretion was related to the prevailing glucose levels across the three hyperglycemic steps in a direct quasilinear manner. We conclude that first-phase insulin secretion is inhibited by short-term modest hyperglycemia, whereas the second-phase insulin secretion increases linearly with hyperglycemia.     

Effect of propofol anesthesia on baroreflex activity in humans

Previous studies have shown that infusions of propofol, a new intravenous anesthetic, were associated with decreased arterial pressure and slow heart rates. To evaluate the role of baroreflex mechanisms in sustaining these conditions, the effects of two infusion rates of propofol (54 and 108 micrograms.kg-1.min-1) to supplement 66% nitrous oxide in oxygen anesthesia were studied in twelve ASA class I patients having a mean age of 34 years. Baroreflex control of heart rate was studied by perturbing the patients' arterial pressure with phenylephrine or sodium nitroprusside. Valsalva maneuvers were used to assess the response of the systemic arterial system. Steady state anesthesia at both infusion rates was not associated with decreased sensitivity of the baroreflex control of heart rate, but resetting of the reflex occurred to allow lower arterial pressures for a given heart rate than in the awake state. During propofol infusions at either rate, the diastolic pressure overshoot normally associated with the relief of raised airway pressure in the Valsalva maneuver was significantly reduced. It is concluded that propofol/nitrous oxide anesthesia is not associated with impairment of baroreflex sensitivity, but that central sympatholytic and/or vagotonic mechanisms enable low heart rates to be sustained despite decreased arterial pressures.     

维生素K在人类骨健康中的作用

骨质疏松及其引发的骨折高发病率巳成为世界公共健康问题,探索营养物质对骨健康的有效性具有重要意义。本文综述的目的是对维生素K在人类骨健康中的防治作用进行评价分析。虽然大量观察性研究显示膳食叶绿醌（维生素K1)或 MK-7与人体骨密度的提高或骨折发生率的下降有着密切关系,但干预性研究尚不能明确维生素K1或MK-4补剂对骨骼的保护作用。此外,研究资料也未证实维生素K营养状况与骨健康之间的关联性。目前相关研究资料不充分,研究方案及研究结 论不一致,维生素K在人类骨健康中的有效防治作用仍存在争议。     

Effects of dopamine on oxygen consumption and gastric mucosal blood flow during cardiopulmonary bypass in humans

We investigated the effects of flow rate and dopamine on systemic oxygen delivery (DO2) oxygen consumption (VO2) and gastric mucosal microcirculatory blood flow (gMCF), measured by laser Doppler flowmetry in 12 patients undergoing mild hypothermic (34 degrees C) cardiopulmonary bypass (CPB). The first intervention comprised increasing CPB flow rates from 2.4 to 3.0 litre min-1 m-2, and the second intervention administering dopamine 6 micrograms kg-1 min-1. Measurements were made before and 10 min after the start of one of the two interventions. The heart remained in cardioplegic arrest throughout the study. There were no significant differences in variables between the two baseline measurements preceding the interventions. The increase in CPB flow rate increased DO2 and gMCF without affecting VO2. At constant flow rate, dopamine also increased gMCF with no change in VO2, DO2 or mean arterial pressure. Our data suggested that dopamine had no flow-independent effect on VO2 and that it increased gMCF during constant flow hypothermic CPB.      

Effect of etomidate on hepatic drug metabolism in humans

The authors studied the effect of etomidate on drug metabolism in vivo in humans and in vitro using human liver microsomes. When these liver microsomes were incubated with different concentrations of etomidate, dose-dependent inhibition of ketamine N-demethylation, a cytochrome P-450-dependent enzymatic process, was produced. Cytochrome P-450 binding spectra displayed type II binding with a UV light absorption maximum (lambda max) at a wavelength of 424 nm in the presence of etomidate. In vivo studies were conducted using ketamine and antipyrine as substrates. Evaluation of antipyrine's pharmacokinetic variables after an intravenous infusion of etomidate (0.34 +/- 0.17 mg/kg) revealed an 18% increase in its elimination half-life (P = 0.04). In addition, there were 16% and 11% decreases in the area under the curve (P = 0.05) and in the clearance rate (P = 0.07) for antipyrine, respectively. In patients administered a bolus dose of ketamine during brief outpatient operations, etomidate produced no significant changes in ketamine's pharmacokinetics compared to thiopental. The authors conclude that the etomidate-induced inhibition of hepatic drug metabolism can prolong the elimination of drugs with low hepatic clearance rates (e.g., antipyrine). However, etomidate would not be expected to alter the rate of elimination of high clearance anesthetics and analgesic drugs (e.g., ketamine, fentanyl).     

Effect of recombinant human erythropoietin on renal function in humans

To assess the effect of recombinant human erythropoietin (r-HuEPO) treatment on renal function, the slopes of the regression lines of the reciprocal of serum creatinine versus time were compared in 26 patients with renal insufficiency (serum creatinine ranged from 2.3 to 11.7 mg/dl) followed for a period of 2.7 to 24 months. Ten patients received r-HuEPO and the anemia was corrected (Group I). Sixteen patients did not receive r-HuEPO. Ten of them were anemic (Group II) and six had normal hematocrits (Group III). All study groups were matched for age, diagnosis and degree of renal insufficiency. All cohorts were followed prospectively (Period B, from the first day of the study to the time of data analysis or dialysis and transplantation); renal function was also examined retrospectively (Period A, from the first day of the study to the time of first renal function measurement). Hematocrit was lowest in Group II control patients, 27%, highest in the Group III control subjects, 43%, and intermediate in Group I EPO-treated patients, 36%. Serum creatinine uniformly increased in all three groups of patients. The rate of progression, as measured by the slopes of the reciprocal of serum creatinine versus time, however, was similar in all three groups of subjects and during both periods. The mean slopes for Group I patients before and after r-HuEPO were, respectively, -0.0058 and -0.0054, that of the control cohorts with low and normal hematocrit during period B were -0.0063 and -0.0010, respectively. Thus, it appeared that neither r-HuEPO administration nor a normal hematocrit accelerated the deterioration of renal function in these patients with renal insufficiency.     

Intestinal hemodynamics during laparotomy: effects of thoracic epidural anesthesia and dopamine in humans

The effects of thoracic epidural anesthesia (TEA) and dopamine infusion (4 micrograms.kg-1.min-1) on superior mesenteric artery blood flow (SMABF), the mesenteric arteriovenous oxygen difference (AVDO2), and the mesenteric venous lactate concentration were studied in nine patients before abdominal aortic reconstruction. Thoracic epidural anesthesia reduced SMABF, as measured by electromagnetic flowmetry, to 77% +/- 8% (mean +/- SEM) of control (P less than 0.05), and mean arterial pressure to 46% +/- 4% of control (P less than 0.01). The mesenteric AVDO2 increased from 27 +/- 3 to 39 +/- 6 mL/L (P less than 0.05) and superior mesenteric venous lactate from 1.03 +/- 0.11 to 1.60 +/- 0.38 mmol/kg (P less than 0.05); systemic AVDO2 and lactate did not change. Dopamine had no significant effect on SMABF and mean arterial pressure before TEA. However, dopamine increased SMABF during TEA (from 77% +/- 8% to 137% +/- 21% of control; P less than 0.01), returned mesenteric AVDO2 to 27 +/- 3 mL/L (P less than 0.05), and elevated mean arterial pressure to 62% +/- 4% of control (P less than 0.05). It is concluded that the decrease in perfusion pressure during TEA reduces SMABF with resultant evidence of intestinal reductive metabolism. The intestinal blood flow during TEA was improved by dopamine.     

Effect of suxamethonium on the auditory evoked response in humans

We have studied the arousal effect of suxamethonium on the auditory evoked response (AER) of the electroencephalogram (EEG) in 40 ASA I and II patients during isoflurane anaesthesia. After induction of anaesthesia, the patient's lungs were ventilated for 20 min with 0.6 MAC end-expiratory isoflurane (0.59-0.77% depending on the age of the patient), and 50% nitrous oxide in oxygen. The patients were then allocated randomly to one of two groups: 21 received suxamethonium 1 mg kg-1, while 19 were given saline. The AER before and after administration of suxamethonium or saline was compared to determine the changes in Pa and Nb amplitudes and latencies. Pa amplitude after suxamethonium increased by 53% (95% confidence interval (CI) 15, 104%) compared with a reduction in Pa amplitude in the saline group of 19% (95% CI, -41, 12%) (P = 0.004) suggesting an arousal effect. Similarly, Nb amplitude increased in the suxamethonium group by 47% (95% CI, 3, 110%) and decreased in the saline group by 11% (95% CI, -33, 19%) (P = 0.03). We conclude that suxamethonium caused arousal according to the AER and postulate that this may have been caused by increased muscle afferent activity after stimulation of muscle spindles, although further studies are required to confirm this.      

Effect of a full bladder on urine production in humans

OBJECTIVE: To demonstrate the reduction in urine production in healthy humans upon bladder distension and to identify the factors responsible for this reduction. MATERIALS AND METHODS: Twelve healthy females were investigated twice in a cross-over designed experiment: once with the urinary bladder empty at the start and once pre-filled to 60% of the maximum bladder capacity. Glomerular filtration rate, effective renal plasma flow, urine content of catecholamines, blood pressure, pulse rate, plasma arginine vasopressin (AVP) and plasma concentration of renine and electrolytes were analysed together with serum osmolality. RESULTS: Three subjects failed to reach maximum bladder capacity during the "full bladder" test and were excluded. The urine production in the "full-bladder" test was significantly lower than the "empty-bladder" test (p = 0.024). In the "full-bladder" test a significant increase in mean blood pressure was found (p=0.01). No further significant changes were demonstrated. CONCLUSIONS: Acute bladder distension causes a reduction in urine production or a "pooling of urine" in the upper urinary tract in healthy humans. The mechanism is unknown.     

异氟醚对健康志愿者脑葡萄糖代谢率的影响

目的 应用正电子发射断层扫描技术(PET),研究吸入不同浓度异氟醚麻醉对健康志愿者脑葡萄糖代谢率(CMRGlu)的影响。方法 选择8名志愿者,每位志愿者分别做三次PET扫描,采用MASEP CPET Plus扫描仪及18F-FDG标记技术测定CMRGIu,第一次在清醒状态下扫描作为对照(清醒组),第二、三次分别吸入0.5 MAC和1.0MAC异氟醚(分别为0.5MAC组和1.0MAC组)后进行。结果 清醒组全脑CMRGlu平均为(30.0±1.1)μmol·100mg-1·min-1,与清醒组比较,0.5MAC组降低全脑CMRGlu24%至(23.3±1.4)μmol·100 mg·min-1(P<0.05),1.0MAC组降低41％至(18.4±0.9)μmol·100mg-1·min-1(P<0.01);脑内各区葡萄糖代谢率(CMRGlu)均显著降低,而以丘脑、楔叶和扣带回降低更为显著(P<0.01);与0.5MAC组比较,1.0MAC组全脑及各脑区rCMRGu进一步降低(P<0.05)。结论 全脑及脑内各区葡萄糖代谢率在吸入异氟醚麻醉时均可显著降低,丘脑、楔叶和扣带回对吸入异氟醚麻醉更为敏感。     

Effect of diet on plasma acid-base composition in normal humans

Steady-state plasma and urine acid-base composition was assessed in 19 studies of 16 normal subjects who ingested constant amounts of one of three diets that resulted in different rates of endogenous noncarbonic acid production (EAP) within the normal range. Renal net acid excretion (NAE) was used to quantify EAP since the two variables are positively correlated in normal subjects. A significant positive correlation was observed between plasma [H+] and plasma PCO2, and between plasma [HCO3-] and plasma PCO2, among the subjects. Multiple correlation analysis revealed a significant interrelationship among plasma [H+], plasma PCO2, and NAE (r = 0.71, P less than 0.001), and among plasma [HCO3-], plasma PCO2, and NAE (r = 0.77, P less than 0.001). The partial correlation coefficients indicated a significant positive correlation between plasma [H+] and NAE, and a significant negative correlation between plasma [HCO3-] and NAE, when plasma PCO2 was held constant. These findings indicate that two factors influence the level at which plasma [H+] is maintained in normal subjects: (1) the steady-state rate of endogenous noncarbonic acid production, and (2) the setpoint at which plasma PCO2 is regulated by the respiratory system. Plasma [HCO3-] is also co-determined by these two factors. In disease states, therefore, both factors must be known before a disturbance in acid-base homeostasis can be excluded.     

Effect of age on MAC in humans: a meta-analysis

It is well known that MAC, the minimum alveolar concentration required to prevent movement in response to surgical incision in 50% of patients, decreases with age. Regression analysis showed that data for humans derived from a comprehensive literature survey were consistent, for age > 1 yr, with log10 MAC decreasing with increasing age at the same rate for all inhaled anaesthetics; approximately equivalent to 6% change per decade of age. With some slight reservation on differences between data from different institutions, the present data for humans are consistent (for age > 1 yr), with the equation MAC = a x 10bx where x = difference in age (in years) from 40, b = -0.00269 (95% confidence limits (CL) -0.0030, -0.0024) and a = MAC at age 40 yr, which, for anaesthetics currently in use clinically, is given by: halothane, 0.75%; isoflurane, 1.17%; enflurane, 1.63%; sevoflurane, 1.80%; desflurane 6.6%; nitrous oxide, 104%; with 95% CL of approximately +/- 7% (+/- 10% for desflurane, +/- 17% for enflurane).      

Effect of riluzole on acute pain and hyperalgesia in humans

Riluzole modulates several transmitter systems which may be involved in nociception. Antinociceptive effects have been shown in animal studies, but there are no human data. Therefore, we have examined the acute analgesic effect of riluzole in a human model of inflammatory pain induced by a thermal injury on the distal leg (47 degrees C, 7 min, 12.5 cm2) in 20 healthy volunteers. Hyperalgesia to mechanical and heat stimuli were examined by von Frey hairs and thermodes. We used a randomized, double-blind, placebo-controlled design, and subjects received riluzole 100 mg or placebo for 2 days with a 14-day interval. The burns produced significant hyperalgesia, but riluzole had no acute analgesic effects in normal or hyperalgesic skin.      

Effect of dopamine on inflammatory status in kidneys of brain-dead rats

BACKGROUND: Brain death has been identified as an independent risk factor for chronic allograft dysfunction. In two independent retrospective clinical studies, we showed that dopamine treatment of brain-dead donors improves long-term kidney graft survival. The mechanisms underlying the protective effects of dopamine treatment in vivo have not been identified. To elucidate the mechanisms underlying the protective effect of dopamine on kidneys of brain-dead donors, we studied a model for brain death in rats. METHODS: In F344 rats, brain death was induced by epidural inflation of a 3F Fogarty catheter. Apneic animals were mechanically ventilated, and clinically relevant dosages of dopamine (2, 6, 10, or 14 microg/kg/min) were given for 6 hr from the onset of brain death. Ventilated, non-brain-dead animals served as controls. RESULTS: Dopamine significantly reduced renal monocyte infiltration and major histocompatibility class II and P-selectin expression in brain-dead animals. It also prevented further up-regulation of the inflammatory markers tumor necrosis factor-alpha and monocyte chemoattractant peptide-1. Concomitantly, the presence of inducible anti-oxidant heme oxygenase-1, known for its cytoprotective effects, was strongly increased by dopamine. CONCLUSION: We identified several mechanisms underlying the protective effects of dopamine treatment on kidney grafts. The identification of these mechanisms may help to design more effective future strategies for treatment of cadaveric kidney donors.     

Effect of dopamine on renal haemodynamics in the denervated dog kidney

Summary The aim of the present study was to explore the potential modulating role of the renal sympathetic nerves in the dopamine-induced vasodilatation in the dog kidney, using the 133-Xenon washout technique.Immediately before and 48 h after combined surgical and local chemical destruction of the sympathetic nerves innervating the left kidney, renal and intrarenal blood flow was monitored in both kidneys. Catecholamine content was determined in control kidneys from untreated dogs, and in the denervated and contralateral, nondenervated kidney 48 h after unilateral sympathectomy.By 48 h after destruction of the sympathetic nerves innervating the left kidney, total renal and particularly cortical flow rates were significantly increased when compared to the right, innervated kidney. Destruction of the sympathetic nerves also resulted in a disappearance of noradrenaline and adrenaline from the kidney and a significant reduction in the content of dopamine in the denervated but an increased level in the innervated kidney.The dopamine-induced increase in renal blood flow was similar in the denervated and in the innervated kidney, suggesting that the sympathetic nerves do not significantly alter the vascular effects of dopamine. The persistence of the dopamine-induced vasodilatation in the sympathectomized kidney supports the concept that dopamine acts directly on postsynaptic, specific dopamine receptors.     

Effect of dopamine infusion on hemodynamics after hepatic denervation

BACKGROUND:. The effects of dopamine (DA) on systemic hemodynamics are better understood than its effects on hepatic hemodynamics, especially after liver denervation occurring during liver transplantation. Therefore, a porcine model was used to study DA's effects on hemodynamics after hepatic denervation. MATERIALS AND METHODS: Fifteen pigs underwent laparotomy for catheter and flow probe placement. The experimental group (n = 7) also underwent hepatic denervation. After 1 week, all pigs underwent DA infusion at increasing doses (3-30 mcg/kg/min) while measuring hepatic parameters [portal vein flow (PVF), hepatic artery flow (HAF), total hepatic blood flow (THBF = HAF + PVF), portal and hepatic vein pressures] and systemic parameters [heart rate (HR), mean arterial pressure (MAP)]. RESULTS: There was a significant increase in HAF from baseline to the 30 mcg/kg/min DA infusion rate (within-subjects P < 0.01), but the differences between the two groups were not significant. PVF and THBF showed large effects (increases) with denervation, but the increase in flow with DA infusion was not present after denervation. Perihepatic pressures were unchanged by denervation or DA. Heart rate differed significantly between the control and denervated animals at baseline, 3, 6, 12 (all P < 0.05), and 30 mcg/kg/min DA (P = 0.10). Control vs denervation MAP at baseline was 100 +/- 4 vs 98 +/- 4 Torr and at 30 mcg/kg/min it was 110 +/- 3 vs 101 +/- 5 mm Hg. CONCLUSIONS: Hepatic flows tended to be higher after denervation. HAF showed similar increases with DA in both control and denervation groups. Increases in PVF and THBF with DA infusion were not present after denervation. HR was significantly decreased and MAP tended to be lower after denervation. The HR and MAP response to DA was similar in both groups. Therefore, both denervation and DA infusion have an effect on systemic and hepatic hemodynamics.     

Effect of cardiopulmonary bypass on pulmonary clearance of adrenomedullin in humans

BACKGROUND: Adrenomedullin is a potent vasodilatory peptide and its plasma concentration increases after cardiopulmonary bypass. We analyzed the contribution of the lung to the disposition of adrenomedullin before and after cardiopulmonary bypass in humans. METHODS: Thirty-five patients undergoing cardiac surgery with cardiopulmonary bypass were studied. Bloods were sampled from the pulmonary artery and left atrium at the following times: prior to systemic heparinization, during pulmonary reperfusion and after cardiopulmonary bypass. Plasma concentrations of total and mature adrenomedullin were measured using an immunoradiometric assay kit specific for human adrenomedullin. Intermediate adrenomedullin was calculated as the difference between total adrenomedullin and mature adrenomedullin. RESULTS: Before cardiopulmonary bypass, mature and intermediate adrenomedullin concentrations were reduced by the pulmonary circulation by approximately 30% and 20%, respectively. However, these effects were not observed during pulmonary reperfusion. Mature, but not intermediate, adrenomedullin was reduced after cardiopulmonary bypass. Furthermore, pulmonary clearance quantity of mature adrenomedullin was significantly enhanced after cardiopulmonary bypass. CONCLUSION: These results indicate that cardiopulmonary bypass temporally impairs the pulmonary clearance of mature and intermediate adrenomedullin, but clearance of mature, not intermediate adrenomedullin is enhanced after cardiopulmonary bypass.