Clinically relevant concentrations of propofol have no effect on adenosine triphosphate-sensitive potassium channels in rat ventricular myocytes

BACKGROUND: Activation of adenosine triphosphate-sensitive potassium (K(ATP)) channels produces cardioprotective effects during ischemia. Because propofol is often used in patients who have coronary artery disease undergoing a wide variety of surgical procedures, it is important to evaluate the direct effects of propofol on K(ATP) channel activities in ventricular myocardium during ischemia. METHODS: The effects of propofol (0.4-60.1 microg/ml) on both sarcolemmal and mitochondrial K(ATP) channel activities were investigated in single, quiescent rat ventricular myocytes. Membrane currents were recorded using cell-attached and inside-out patch clamp configurations. Flavoprotein fluorescence was measured to evaluate mitochondrial oxidation mediated by mitochondrial K(ATP) channels. RESULTS: In the cell-attached configuration, open probability of K(ATP) channels was reduced by propofol in a concentration-dependent manner (EC(50) = 14.2 microg/ml). In the inside-out configurations, propofol inhibited K(ATP) channel activities without changing the single-channel conductance (EC(50) = 11.4 microg/ml). Propofol reduced mitochondrial oxidation in a concentration-dependent manner with an EC(50) of 14.6 microg/ml. CONCLUSIONS: Propofol had no effect on the sarcolemmal K(ATP) channel activities in patch clamp configurations and the mitochondrial flavoprotein fluorescence induced by diazoxide at clinically relevant concentrations (< 2 microm), whereas it significantly inhibited both K(ATP) channel activities at very high, nonclinical concentrations (> 5.6 microg/ml; 31 microm).     

咪唑安定及异丙酚对大鼠心肌细胞电生理活动的影响

目的 观察咪唑安定复合酚对大鼠心室肌细胞电生理活动的影响。方法 急性分离的大鼠单个心室肌细胞，采用膜片钳技术，观察咪唑安定、异丙酚及其复合应用时对Ｌ－爱道电流（Ｉｃａ）及动作电位的影响。结果 咪唑安定３μｍｏｌ．Ｌ＾－１和１５０μｍｏｌ．Ｌ＾－１，异丙酚５０μｍｏｌ．Ｌ＾－１和２５０μｍｏｌ．Ｌ＾－１分一ｃａ较用药前下降１８．８％和４３．８％（Ｐ均〈０．０５，ｎ＝５），咪唑安定、异丙酚及其复药复合     

Comparison of effects of propofol and midazolam at sedative concentrations on sympathetic tone generation in the isolated spinal cord of neonatal rats

BACKGROUND: Propofol and midazolam are common sedatives for critically ill patients. Little is known about the effects of propofol and midazolam on central sympathetic activity when drug concentrations in extracellular milieu are under precise control. Previous work using an in vitro neonatal rat splanchnic nerve-spinal cord preparation has demonstrated that tonic sympathetic activity is generated spontaneously in the thoracic spinal cord. The aim of this study was to investigate the concentration effects of propofol and midazolam on spinally generated sympathetic activity. METHODS: Using an in vitro neonatal rat splanchnic nerve-spinal cord preparation that allows the precise control of drug concentrations, the central sympathetic effects elicited by the application of propofol (10-640 microM) and midazolam (10-640 microM) were compared. RESULTS: There was a prompt decrease in sympathetic activity on application of propofol or midazolam in a concentration-dependent manner. A significant decrease in sympathetic activity was observed on application of propofol at 80-640 microM; however, the application of propofol at 10-40 microM caused only a slight alteration in activity. The sympathetic activity was not altered significantly by 10 microM of midazolam, but the application of midazolam at 20-640 microM caused a significant decrease in activity. Thus, in these experimental conditions, the minimum concentration of propofol causing a significant decrease in sympathetic activity was 80 microM and that of midazolam was 20 microM. CONCLUSIONS: The current findings suggest that the administration of 9-19 microM of propofol or 0.7-0.9 microM of midazolam, the clinically relevant concentrations for sedation, does not alter central sympathetic outflow at the spinal cord level. However, propofol at a concentration of 86 microM, which could be achieved by a single-bolus loading dose to induce sedation, depresses central sympathetic activity.     

丙泊酚与咪达唑仑对离体细胞内毒素损伤后炎性反应的影响

目的 探讨丙泊酚与咪达唑仑对离体细胞内毒素损伤后炎性反应的影响.方法 将内毒素诱导血清分为A、B、C、D4组:A组:对照组;B组:丙泊酚+咪达唑仑组,加入丙泊酚和咪达唑仑配制成含有两药(各)10μmol/L;C组:咪达唑仑组含咪达唑仑10μmol/L;D组:丙泊酚组含丙泊酚10μmol/L.分别在给药前(T0)、给药后即刻(T1)、80min(T2)、120min(T3)、180min(T4)时间点采用化学发光法进行测定肿瘤坏死因子α(TNF-α)的浓度.结果 T0-T2时,各组间血清TNF活性无统计学差异,T3-T4时各试验组TNF活性均明显低于对照组(3121.0±157.8和1720.0±902.0),各试验组之间差异无统计学意义.结论 丙泊酚与咪达唑仑能较好的抑制离体细胞内毒素损伤后炎性因子的释放.     

Clinically significant concentrations of local anesthetics inhibit Staphylococcus aureus in vitro

This study explores which concentrations of local anesthetics might be expected to inhibit the growth of Staphylococcus aureus. Serial dilutions were made of 0.5% and 0.75% bupivacaine, 2% and 5% lidocaine, 2% and 3% chloroprocaine, and 0.2% and 1% ropivacaine. To each concentration of local anesthetic solution, Mueller Hinton broth medium and Staphylococcus aureus were added. The resulting solutions were incubated and then observed for growth 24 and 48 h later. The minimum concentrations of the local anesthetics that could inhibit growth of Staphylococcus aureus were 0.25% bupivacaine, 1.25% lidocaine and 0.75% chloroprocaine. The inhibitory concentration of ropivacaine could not be determined because the more concentrated solutions precipitated in the Mueller Hinton broth. Local anesthetics may help protect against epidural abscess formation if they are used in sufficiently high concentrations. This effect may help explain the very low reported incidence of epidural abscess.     

Dexamethasone does not alter in vitro antibacterial efficacy of gentamicin.

OBJECTIVES: Aminoglycoside ototoxicity may be mitigated by administration of dexamethasone; however, dexamethasone could theoretically impair its antibacterial properties. The purpose of this experiment was to determine if dexamethasone decreases the antibacterial activity of gentamicin against Pseudomonas aeruginosa (PA) and Staphylococcus aureus (SA). STUDY DESIGN: In vitro microbiological assay. METHODS: Four separate trials of minimum inhibitory concentration (MIC) testing were performed for gentamicin against five PA strains and six SA strains, with and without the addition of high and low concentrations of dexamethasone. RESULTS: MICs were not changed by more than one dilution with the addition of either high or low concentrations of dexamethasone for any of the PA and SA strains. CONCLUSION: Dexamethasone does not impair the antibacterial efficacy of gentamicin for PA and SA. This supports the role of dexamethasone as an oto-protectant with aminoglycoside therapy.     

Conscious sedation with midazolam or propofol does not alter left ventricular diastolic performance in patients with preexisting diastolic dysfunction: a transmitral and tissue Doppler transthoracic echocardiography study

The effects of midazolam and propofol on left ventricular (LV) diastolic function have not been evaluated in humans. We tested the hypothesis that midazolam and propofol alter LV diastolic function evaluated with transmitral and tissue Doppler transthoracic echocardiography in patients with normal LV systolic function in the presence and absence of preexisting diastolic dysfunction. After IRB approval and informed consent, patients (n = 34) with normal or reversed transmitral blood flow velocity E-to-A ratios received 3 escalating doses of midazolam (0.025, 0.05, and 0.1 mg/kg) or propofol (0.25, 0.5, and 1.0 mg/kg) over 10 s at 5-min intervals. Hemodynamic variables and indices of diastolic function were recorded 3 min after each dose of midazolam and propofol. Patients with diastolic dysfunction demonstrated decreased ratios of peak transmitral E-to-A wave velocity and their corresponding time-velocity integrals as compared with normal patients. Reductions in anterior and posterior mitral annulus E/A ratios were also present. Midazolam and propofol did not further alter indices of LV diastolic function in patients with impaired early LV filling. The results indicate that sedation with midazolam or propofol does not affect indices of LV diastolic performance in healthy patients and those with preexisting diastolic dysfunction. IMPLICATIONS: Sedation with midazolam or propofol does not alter indices of left ventricular diastolic function in healthy patients and those with preexisting left ventricular filling abnormalities as evaluated by transthoracic echocardiography.     

Neuroprotective properties of propofol and midazolam, but not pentobarbital, on neuronal damage induced by forebrain ischemia, based on the GABAA receptors

BACKGROUND: The mechanism of the neuroprotective effects of propofol was compared to two other types of intravenous (i.v.) anesthetics (i.e., benzodiazepine; midazolam and barbiturate; pentobarbital) using Mongolian gerbils focusing on GABA receptor subtypes. METHODS: Neuronal injury was induced by a 4-min occlusion of the common carotid arteries followed by reperfusion. One week after occlusion, animals were transcardially perfused for histochemistry. Neuronal death in four brain regions was evaluated by direct visual counting of acidophilic neurons. RESULTS: Seven days after this ischemic episode, severe neuronal injury was measured in the hippocampal CA1 area (> 98% of total cells damaged) and parietal cortex (> 35%). Also lateral thalamus and caudate putamen were damaged but to a lesser extent (about 10%). The neuronal injury in these areas was significantly attenuated by propofol, midazolam and the GABAA agonist, muscimol, intraperitoneally administered 15 min prior to ischemia. This neuroprotective property, however, was lacking with pentobarbital and GABAB agonist baclofen. Concomitant pretreatment with subthreshold doses of propofol and muscimol significantly reduced the amount of cell death induced by brain ischemia. On the other hand, pretreatment with the GABAA antagonist bicuculline significantly inhibited the neuroprotective effects of propofol. However, a GABAB antagonist, phaclofen, was without effect on neuronal damage and on neuronal protection of propofol. CONCLUSION: These results indicate that activation of GABAA receptors, which include the specific binding subunits for propofol and midazolam, but not pentobarbital, plays a role in the inhibition of neuronal death induced by brain ischemia.     

Flumazenil reduces the duration of thiopentone but not of propofol anaesthesia in humans

The effect of flumazenil (F) on the duration of anaesthesia produced by a single dose of thiopentone (T) and propofol (P) was investigated in a placebo-controlled double-blind trial. Eighty-four patients anaesthetized with N₂O in O₂ and either thiopentone 7 mg · kg^?1 or propofol 3 mg · kg^?1 for minor gynaecological procedures were studied. Patients were randomly allocated to pretreatment with either 0.5 mg of flumazenil (F) or 5 ml of normal saline (NS) in one of the following groups: T/NS, T/F, P/NS, or P/F. Anaesthetic requirements were assessed by recording the time between the injection of anaesthetic and the first movement observed during the procedure. The time elapsed from the administration of thiopentone to the first movement was 6.5 ± 1.6 min for the T/NS group and 5.3 ± 2.4 min for the T/F group (P < 0.05). The first movement after propofol administration was observed at 7.0 ± 2.2 min in the P/NS group and at 7.1 ± 4.5 min in the P/F group (NS). These data suggest that pretreatment with 0.5 mg of flumazenil iv reduces the duration of thiopentone but not of propofol anaesthesia.     

Sorbinil prevents diabetes-induced increases in vascular permeability but does not alter collagen cross-linking

In recent studies we have demonstrated a marked increase in albumin permeation of new vessels formed by angiogenesis (in subcutaneous tissue) in the diabetic milieu. Likewise, lysyl oxidase-mediated collagen cross-linking is markedly increased in the scar tissue associated with angiogenesis. The present studies were undertaken to determine whether sorbinil, a chemical inhibitor of aldose reductase that has been shown to prevent and reverse diabetic cataracts and neuropathy, also could prevent the vascular permeability and collagen cross-linking changes in this model. Vascular permeation by 125I-BSA, collagen cross-linking, and tissue levels of sorbitol, myo-inositol, and scyllo-inositol were assessed in male Sprague-Dawley rats 3 wk after injection of streptozocin and induction of angiogenesis and collagen synthesis in polyester fabric implanted subcutaneously. Sorbinil (approximately 25 mg/kg/day) added to the diet of diabetic rats reduced the diabetes-induced increases in albumin permeation by 80%, completely prevented diabetes-induced changes in tissue levels of sorbitol and myo-inositol, and markedly reduced diabetes-induced changes in tissue levels of scyllo-inositol. In contrast, sorbinil had no effect on plasma glucose levels or collagen solubility (an index of collagen cross-linking). These observations indicate that increased vascular permeability associated with diabetes is linked to imbalances in sorbitol/inositol metabolism. These findings also indicate that diabetes-induced increases in vascular permeability and in collagen cross-linking are independent phenomena and diabetes-induced increases in vascular permeability are largely preventable by treatment with an aldose reductase inhibitor in the face of high plasma glucose levels.     

异丙酚对离体SD大鼠乳头肌收缩性能的影响

目的：观察异丙酚不同浓度时在不同时间对乳头肌收缩性能的影响并和咪唑安定进行比较。方法：２０条乳头肌随机分成２组，分别给予异丙酚１０、２０、３０、４０μｇ／ｍｌ和咪唑安定１０、２０、５０、１００μｇ／ｍｌ，观察等长张力峰值（ＰＴ），张力上升最大速度（ｄＴ／ｄｔｍａｘ），张力下降最大速度（－ｄＴ／ｄｔｍａｘ）和心肌收缩成份的缩短速度（Ｖｃｅ）在用药后的变化。结果：当异丙酚的浓度达到４０μｇ／ｍｌ，作用时间达到９．５±１．５８分，咪唑安定的浓度达到１００μｇ／ｍｌ，作用时间达到１４．５±１．５８分时即可完全抑制心肌收缩，两药在浓度和作用时间上均有显著差异（Ｐ＜０．０５）。结论：对于离体的ＳＤ大鼠乳头肌，异丙酚比咪唑安定产生的负性肌力作用更大。     

Mild hypothermia, but not propofol, is neuroprotective in organotypic hippocampal cultures

The neuroprotective potency of anesthetics such as propofol compared to mild hypothermia remains undefined. Therefore, we determined whether propofol at two clinically relevant concentrations is as effective as mild hypothermia in preventing delayed neuron death in hippocampal slice cultures (HSC). Survival of neurons was assessed 2 and 3 days after 1 h oxygen and glucose deprivation (OGD) either at 37 degrees C (with or without 10 or 100 microM propofol) or at an average temperature of 35 degrees C during OGD (mild hypothermia). Cell death in CA1, CA3, and dentate neurons in each slice was measured with propidium iodide fluorescence. Mild hypothermia eliminated death in CA1, CA3, and dentate neurons but propofol protected dentate neurons only at a concentration of 10 microM; the more ischemia vulnerable CA1 and CA3 neurons were not protected by either 10 microM or 100 microM propofol. In slice cultures, the toxicity of 100 muM N-methyl-D-aspartate (NMDA), 500 microM glutamate, and 20 microM alpha-amino-5-methyl-4-isoxazole propionic acid (AMPA) was not reduced by 100 microM propofol. Because propofol neuroprotection may involve gamma-aminobutyric acid (GABA)-mediated indirect inhibition of glutamate receptors (GluRs), the effects of propofol on GluR activity (calcium influx induced by GluR agonists) were studied in CA1 neurons in HSC, in isolated CA1 neurons, and in cortical brain slices. Propofol (100 and 200 microM, approximate burst suppression concentrations) decreased glutamate-mediated [Ca2+]i increases (Delta[Ca2+]i) responses by 25%-35% in isolated CA1 neurons and reduced glutamate and NMDA Delta[Ca2+]i in acute and cultured hippocampal slices by 35%-50%. In both CA1 neurons and cortical slices, blocking GABAA receptors with picrotoxin reduced the inhibition of GluRs substantially. We conclude that mild hypothermia, but not propofol, protects CA1 and CA3 neurons in hippocampal slice cultures subjected to oxygen and glucose deprivation. Propofol was not neuroprotective at concentrations that reduce glutamate and NMDA receptor responses in cortical and hippocampal neurons.     

Reduced absorption of45calcium from isolated duodenal segmentsin vitro in juvenile but not adult X-linked hypophosphatemic mice

Summary In juvenile X-linked hypophosphatemic (Hyp) mice, whole body calcium balances are significantly lower than in genetically normal mice. This is associated with low duodenal vitamin D-dependent calcium-binding protein and a failure of skeletal mineralization. To seek more specific evidence of an intestinal defect in these mice, absorption of⁴⁵Ca was measured in isolated duodenal segmentsin vivo in mice from 2–13 weeks of age. The duodenum was isolated by sutures and⁴⁵Ca was injected into the lumen in 150 mM NaCl and 2 mM CaCl₂ at pH=7.2. Absorption was measured by the amount of isotope remaining in the lumen and by the plasma isotope level. HemizygousHyp male and heterozygousHyp female mice absorbed significantly less⁴⁵Ca at 4 and 7 weeks of age than genetically normal mice whileHyp mice at 2, 10, and 13 weeks of age were not significantly affected. At 4 and 7 weeks of age, theHyp mice also had significantly reduced plasma radioactivity midway through the collection period as well as at the end of the period. To explore a possible mechanism for this malabsorption, 1,25(OH)₂-vitamin D receptors were measured in cytosol prepared from 4-week-old normal andHyp duodenum. There were non-significant differences between the normal andHyp mice in both binding affinity, K_d, and the number of receptors, n_max. In conclusion, juvenileHyp mice at 4 and 7 weeks of ages malabsorbed calcium from their duodenum.Hyp mice younger than this period were not affected nor were adultHyp mice. This delay in the development of calcium absorption was not caused by a delay in the appearance of intestinal receptors for 1,25(OH)₂D.     

Flumazenil does not antagonize the cardiac effects of midazolam in the isolated rat heart-lung preparation

We examined the effects of midazolam and flumazenil on cardiac function and metabolism in the isolated rat heart-lung preparation. Wistar rats were divided into five groups (each group:n=8) as follows: (1) control (saline); (2) flumazenil (1.3×10⁻⁵M); (3) flumazenil (10⁻⁴M); (4) midazolam (60μg·ml⁻¹); and (5) midazolam (60μg·ml⁻¹) and flumazenil (1.3×10⁻⁵M). Systolic blood pressure and calculated left ventricular dP/dt maximum in the midazolam or midazolam conbined with flumazenil groups increased significantly in comparison with those in the control group. Heart rate in the midazolam group was lower than that in the control group. However, in the flumazenil group, there were no effects on the hemodynamics. There were no significant differences in the myocardial tissue concentration of ATP, lactate, and glycogen in all groups. In this study, midazolam decreased heart rate; however, flumazenil had no effect on the heart, nor did it antagonize the cardiac effects of midazolam. These results suggest that flumazenil has no effect on the peripheraltype benzodiazepine receptor of the myocardium.     

Systemic lidocaine decreases the Bispectral Index in the presence of midazolam, but not its absence

Study ObjectiveTo evaluate the effects of intravenous (IV) lidocaine on the Bispectral Index (BIS) in the presence or absence of midazolam.DesignProspective, randomized, double-blinded, placebo-controlled clinical study.SettingOperating room of a university hospital.Patients96 ASA physical status 1, 2, and 3 patients undergoing general anesthesia.InterventionsPatients were assigned to one of 6 treatment groups to receive IV midazolam (0.03 mg/kg) or placebo, followed 5 minutes later by one of three IV preinduction doses of lidocaine: 0.5, 1.0, or 1.5 mg/kg.MeasurementsBIS values were recorded before administration of lidocaine and at 30-second intervals afterwards for three minutes. The primary endpoint was the average BIS level recorded.Main ResultsBaseline BIS values were lower in the midazolam group (94 ± 4 vs. 90 ± 7, P < 0.001). There was no significant decrease in BIS values in the placebo group for any of the three lidocaine doses. However, in the midazolam groups, significant decreases in BIS levels versus baseline values were measured.ConclusionIV lidocaine decreases BIS in the presence of midazolam, suggesting that the effect of lidocaine on BIS is not direct, but rather results from modulation by midazolam.     

不同浓度异丙酚对体外人辅助性T淋巴细胞分化的影响

目的 探讨不同浓度异丙酚对体外人辅助性T淋巴细胞(Th细胞)分化的影响.方法 健康志愿者20名,男性9名,女性11名,年龄20～50岁,体重50～70 kg,每名健康志愿者分别采集外周静脉血20ml,进行全血培养,采用随机区组设计,分别接受下述处理:空白对照组(C组)、不同浓度异丙酚组[P1组(1 μg/ml)、P2组(4 μg,ml)、P3组(16 μg/ml)]、不同浓度异丙酚赋形剂组[I1 组(0.1μl/ml)、I2组(0.4μl/ml)、I3组(1.6 μl/ml)].每份血样培养于无菌24孔培养板中,依次加入上述药物培养24 h后加入氟波醇乙酯、离子霉素及蛋白质转运抑制剂刺激4 h,采用三色流式细胞技术检测全血中Th1细胞及Th2细胞的亚群比例,并计算Th1细胞与Th2细胞比值(Th1/Th2).结果 与C组比较,P3组Th1细胞亚群比例和Th1/Th2升高,I3组Th2细胞亚群比例降低(P＜0.05),其余组各指标差异无统计学意义(P＞0.05);与P1组比较,p3 组Th1细胞亚群比例和Th1/Th2升高(P＜0.05);与I3组比较,p3 组Th1细胞、Th2细胞的亚群比例升高(P＜0.05).结论 异丙酚16 μg/ml可使Th细胞向Th1细胞分化增加,1.4 μg/ml对Th细胞分化无影响.     

Pentobarbitone, but not propofol, produces pre-emptive analgesia in the rat formalin model

Injection of formalin into the hindpaw of a rat induces a biphasicresponse in pain-related behaviours, such that C-fibre activationduring phase 1 triggers a state of central sensitization characterizedby a longer lasting phase 2. As the inhibitory neurotransmittergamma-aminobutyric acid (GABA) may participate in processingof nociceptive inputs, we hypothesized that pentobarbitone andpropofol, i.v. anaesthetics with known GABA_A agonist properties,would inten'ere with development of central sensitization andthereby modify the phase 2 hyperalgesic response. Pentobarbitoneadministered i. v. before injection of formalin produced dose-dependentsuppression of phase 2, even though animals had recovered fromanaesthesia, whereas it had substantially less effect when givenafter phase 1 had resolved. Picrotoxin, a GABA_A antagonist,reversed the effect of pentobarbitone on phase 2 pain behaviourbut was itself a mild analgesic. In contrast, propofol had noeffect on phase 2 formalin-induced pain behaviour. Thus we concludethat pentobarbitone, but not propofol, produced pre-emptiveanalgesia in this model, presumably by suppressing noxious stimulation-inducedcentral sensitization via activation of GABA_A receptors. ^*Present address: Department of Anesthesia, Teikyo University,Ichihara Hospital, 3426-3 Anesaki, Ichihara, Chiba 299-01, Japan     

Lidocaine reduces ischaemic but not reperfusion injury in isolated rat heart

The local anaesthetic lidocaine protects the myocardium in ischaemia–reperfusionsituations. It is not known if this is the consequence of ananti-ischaemic effect or an effect on reperfusion injury. Therefore,we investigated the effect of two concentrations of lidocaineon myocardial ischaemia–reperfusion injury and on reperfusioninjury alone. We used an isolated rat heart model where heartrate, ventricular volume and coronary flow were kept constant.Hearts underwent 45 min of low-flow ischaemia followed by 90min reperfusion. Two groups received lidocaine 1.7 or 17 µgml^–1 starting 5 min before the onset of reperfusion. Intwo additional groups, lidocaine infusion started 5 min beforelow-flow ischaemia. In all groups, lidocaine administrationwas stopped after 15 min of reperfusion. One group served asan untreated control (n=11 in each group). Left ventriculardeveloped pressure (LVDP) and total creatine kinase release(CKR) were measured. Lidocaine administration during ischaemiaand reperfusion led to an improved recovery of LVDP during reperfusion(1.7 µg ml^–1, 54 (SEM 10) mm Hg; 17 µg ml^–1,71 (9) mm Hg at 30 min of reperfusion; both significantly differentfrom control (21 (4) mm Hg) (P<0.05)) and a reduced CKR (1.7µg ml^–1, 79 (13) IU; 17 µg ml^–1, 52(8) IU at 30 min of reperfusion; both significantly differentfrom control (130 (8) IU (P<0.05)). Lidocaine given duringearly reperfusion only, affected neither LVDP during reperfusion(1.7 µg ml^–1, 19 (6) mm Hg (P=1.0); 17 µgml^–1, 36 (8) mm Hg (P=0.46)) nor CKR (156 (21) IU (P=0.50)and 106 (14) IU (P=0.57)). We conclude that lidocaine protectsthe myocardium against ischaemic but not against reperfusioninjury in the isolated rat heart. Br J Anaesth 2001; 86: 846–52     

Coating of extracorporeal circuit with heparin does not prevent sequestration of propofol in vitro

Propofol is sequestered in extracorporeal circuits, but the factors responsible for the phenomenon are mostly unknown. We have compared two extracorporeal circuits (oxygenators, reservoirs and tubings) coated with heparin with two corresponding uncoated circuits for their capacity to sequester propofol in vitro. Three experiments were conducted with each circuit. The circuit was primed with a mixture of Ringer's acetate solution and whole blood, and the study conditions (pump flow, temperature, pH) were standardized. Propofol was added to the solution to achieve a concentration of 2 micrograms ml-1. These studies were followed with concentrations of 10- and 100-fold to assess possible saturation of propofol binding. Serial samples were obtained from the circulating solution for measurement of propofol concentration. Propofol concentrations decreased to 22-32% of the initial predicted concentration of 2 micrograms ml-1 in the circuits (no significant difference between circuits). With greater concentrations, the circuits did not become saturated with propofol, even with the highest predicted concentration of 200 micrograms ml-1. We conclude that propofol was sequestered in extracorporeal circuits in vitro, irrespective of coating the circuit with heparin.