Isoflurane-induced protection against myocardial stunning is independent of adenosine 1 (A(1)) receptor in isolated rat heart

Volatile anaesthetics can pharmacologically enhance the recoveryof stunned myocardium, but the mechanism is still unknown. Thisstudy sought to determine whether isoflurane attenuates myocardialstunning, and whether the myocardial protection of isofluraneis mediated by adenosine A₁ receptors. Five groups (n=8) ofisolated rat hearts were studied in the Langendorff apparatus.The control groups underwent 20-min ischaemia with or withoutadenosine receptor antagonist (DPCPX, A₁selective) treatment(Cont group and DPCPX group). In the isoflurane groups, isoflurane(1.5 MAC) was present throughout the experiment (Iso group)and DPCPX (200 nM) was administered from 10 min before ischaemia(Iso+DPCPX(pre-I) group) or the beginning of reperfusion (Iso+DPCPX(post-I)group) to the end of experiment. The isoflurane groups had alower end-diastolic pressure than the control groups (P<0.05).Developed pressure recovered to 77, 76, and 82% in Iso, Iso+DPCPX(pre-I)and Iso+DPCPX(post-I) groups, respectively (P<0.05 comparedwith control groups). LV+dp/dt_max recovered to 53, 86, 81, 84,and 60% of pre-ischaemic values in Cont, Iso, Iso+DPCPX(pre-I),Iso+DPCPX(post-I), and DPCPX groups. LV-dp/dt_min recovered to55, 84, 83, 81, and 62%, respectively. Both LV+dp/dt_max andLV-dp/dt_min were significantly different (P<0.05) betweencontrol and isoflurane groups during reperfusion. There wereno significant differences among the isoflurane groups. Ourdata show that isoflurane enhances the post-ischaemic functionalrecovery of isolated rat heart and that block of A₁ receptorsdoes not abolish the beneficial effects of isoflurane. We concludethat A₁receptors are not involved in isoflurane-induced myocardialprotection in the isolated rat heart. Br J Anaesth 2001; 87: 258–65     

Can isoflurane mimic ischaemic preconditioning in isolated rat heart?

Ischaemic preconditioning can protect the myocardium againstischaemic injury by opening of the adenosine triphosphate (ATP)-sensitivepotassium (K_ATP) channel. Isoflurane is also thought to openthis channel. The present investigation tested the hypothesisthat pre-ischaemic treatment with isoflurane mimics ischaemicpreconditioning (producing chemical preconditioning) and therebyprotects the myocardium against ischaemic injury in an isolatedrat heart model. Control hearts underwent 30 min of globalno-flow ischaemia followed by 60 min of reperfusion. Thehearts of the preconditioning group underwent two 5 minperiods of no-flow ischaemia interspersed with 5 min ofreperfusion before the sustained ischaemia. In three additionalgroups, hearts were subjected to 15 min of 1.5 minimalalveolar concentration (MAC) of isoflurane (ISO-1), 15 min 3MAC (ISO-2) or 25 min 1.5 MAC (ISO-3) of isoflurane followedby 5 min washout before the global ischaemia. Left ventricular(LV) developed pressure and creatine kinase release were measuredas variables of myocardial performance and cellular injury,respectively. Recovery of LV developed pressure was improvedafter ischaemic preconditioning [after 60 min reperfusion,mean 63 (SEM 6)% of baseline] compared with the control group[18 (4)% P<0.01] but not by isoflurane, independently ofconcentration or duration of administration [ISO-1, 17 (2)%,P=0.99 vs control; ISO-2, 12 (3)%, P=0.64; ISO-3, 4 (1)%, P=0.06].Total creatine kinase release over 1 h of reperfusion wasnot significantly different between control [251 (36) U g^–1dry weight] and all isoflurane groups [ISO-1, 346 (24) U g^–1,P=0.30; ISO-2, 313 (33) U g^–1, P =0.73; ISO-3, 407(40) U g^–1, P=0.03]. These results indicate thatpre-ischaemic administration of isoflurane does not cause anaesthetic-inducedpreconditioning in the isolated rat heart. Br J Anaesth 2001; 86: 269–71     

Sevoflurane preconditioning at 1 MAC only provides limited protection in patients undergoing coronary artery bypass surgery: a randomized bi-centre trial

BACKGROUND: Volatile agents can mimic ischaemic preconditioning leading to a decrease in myocardial infarct size. The present study investigated if a 15 min sevoflurane administration before cardiopulmonary bypass (CPB) has a cardioprotective effect in patients undergoing coronary surgery. METHODS: Seventy-two patients were randomized in two centres. The intervention group (S) received 1 MAC sevoflurane administrated via the ventilator for 15 min followed by a 15 min washout before CPB, the control group did not. The primary outcome was the postoperative troponin Ic peak. A biopsy of the atrium was taken during canulation for enzyme dosages. Results are expressed as mean (SD). RESULTS: Neither troponin Ic nor tissular enzyme measurement exhibited any difference between the groups: peak of troponin Ic was 4.4 (5.6) in S group vs 5.2 (6.6) ng ml(-1) in control group (ns). Intratissular ecto-5'-nucleotidase activity was 7.1 (4.3) vs 8.5 (11.9), protein kinase C activity was 27.1 (15.7) vs 29.2 (28.7), tyrosine kinase activity was 101 (54.1) vs 98.5 (63.3), and P38 MAPKinase activity was 131.1 (76.1) vs 127.1 (86.8) nmol mg protein(-1) min(-1) in S group and control group, respectively (ns). However there were fewer patients with low postoperative cardiac index in S group (11% in S vs 35% in control group, P < 0.05) when considering the per protocol population. In S group, 25% of patients required an inotropic support during the postoperative period, vs 36% of patients in control group (ns). CONCLUSIONS: This study did not show a significant preconditioning signal after 15 min of sevoflurane administration. The 15 min duration might be too short or the concentration of sevoflurane too low to induce cardioprotection detected by troponin I levels.     

Effect of lidocaine on ischaemic preconditioning in isolated rat heart

Background. Lidocaine is frequently used as an agent to treatventricular arrhythmias associated with acute myocardial ischaemia.Lidocaine is a potent blocker not only of sodium channels, butalso of ATP-sensitive potassium channels. The opening of thesechannels is a key mechanism of ischaemic preconditioning. Weinvestigated the hypothesis that lidocaine blocks the cardioprotectioninduced by ischaemic preconditioning. Methods. Isolated rat hearts (n=60) were subjected to 30 minof no-flow ischaemia and 60 min of reperfusion. Control hearts(CON) underwent no further intervention. Preconditioned hearts(PC) received two 5-min periods of ischaemia separated by 10min of reflow before the 30 min ischaemia. In three groups,lidocaine was infused at concentrations of 2, 10 or 20 µgml^–1 for 5 min before the preconditioning ischaemia. Leftventricular developed pressure (LVDP) and infarct size (IS)(triphenyltetrazolium choride staining) were measured as variablesof ventricular function and cellular injury, respectively. Results. PC reduced IS from 24.8 (SEM 4.1) % to 4.0 (0.7) %of the area at risk (P<0.05). Adding 2 or 10 µg ml^–1lidocaine had no effect on IS compared with PC alone (3.7 (0.7)%, 6.9 (1.8) %). Adding 20 µg ml^–1 lidocaine increasedIS to 14.1 (2.5) % compared with PC (P<0.05). Baseline LVDPwas similar in all groups (111.4 (2.1) mm Hg). Compared withCON, PC improved functional recovery (after 60 min of reperfusion;52.3 (5.9) mm Hg vs 16.0 (4.0) mm Hg, P<0.01). The improvedventricular function was not influenced by addition of 2 or10 µg ml^–1 lidocaine (47.3 (5.7) mm Hg, not significant;45.3 (7.3) mm Hg, not significant), but was blocked by the infusionof 20 µg ml^–1 lidocaine (22.5 (8.0) mm Hg, P<0.01vs PC). Conclusions. Lidocaine blocks the cardioprotection induced byischaemic preconditioning only at supratherapeutic concentrations.     

Blood/gas partition coefficients of halothane,isoflurane and sevoflurane in horse blood

Background. Blood/gas partition coefficients (_b/g) for volatileagents in horse blood are reported for halothane but not forisoflurane and sevoflurane. We measured the _b/g of halothane,isoflurane and sevoflurane in the blood of fasted horses. Thecorrelation with age, weight and some haematological and biochemicalvariables was studied. The temperature correction factor forisoflurane solubility was calculated. Methods. Twenty-four horses were randomly allocated to halothane(n=8), isoflurane (n=8) or sevoflurane (n=8). Blood sampleswere taken after 10 h’ fasting. Calculation of _b/g wasbased on the measurement of anaesthetic partial pressures inblood at 37 °C, which was achieved with tonometer equilibrationand headspace gas chromatography. Results. Mean _b/g was 1.66 (SD 0.06) for halothane, 0.92 (0.04)for isoflurane, and 0.47 (0.03) for sevoflurane. The _b/g valueswere all significantly lower than in humans (P<0.001). Nocorrelation was found between _b/g and weight, age, haematocrit,plasma triglycerides, cholesterol or total bilirubin. The changein isoflurane solubility per 1 °C temperature increase was–2.63 (0.13)%. Conclusion. The _b/g values of halothane, isoflurane and sevofluranein fasted horses are significantly lower than those reportedin humans. The _b/g for halothane in this study agrees with valuesreported in the literature but a positive correlation with plasmatriglycerides could not be confirmed. Knowledge of _b/g can refinemodels of anaesthetic uptake. Br J Anaesth 2003; 91: 276–8     

Prediction of volatile anaesthetic solubility in blood and priming fluids for extracorporeal circulation

Volatile anaesthetics are often used during cardiopulmonarybypass (CPB). To understand the kinetics of inhaled anaestheticsduring CPB, anaesthetists should understand changes in bloodsolubility caused by fluid use. We set out to predict the solubilityof three volatile anaesthetics, desflurane, isoflurane and halothane,during CPB by determining: (i) their solubility in fresh wholeblood and eight CPB priming fluids at 37°C; (ii) the effectof temperature on the solubility of these anaesthetics in lactatedRinger’s, gelofusin, banked blood and plasma; (iii) theirsolubility in different mixtures of these four priming fluidsat different temperatures; and (iv) their estimated and actualsolubility in blood during hypothermic CPB. We calculated solubilityusing a concept of volume fraction partition coefficient andcompared estimated and measured solubilities. For the threeanaesthetics tested, solubilities are in the order: fresh wholeblood     

Effects of sevoflurane on dopamine, glutamate and aspartate release in an in vitro model of cerebral ischaemia

Release of excitatory amino acids and dopamine plays a centralrole in neuronal damage after cerebral ischaemia. In the presentstudy, we used an in vitro model of ischaemia to investigatethe effects of sevoflurane on dopamine, glutamate and aspartateefflux from rat corticostriatal slices. Slices were superfusedwith artificial cerebrospinal fluid at 34°C and episodesof ‘ischaemia’ were mimicked by removal of oxygenand reduction in glucose concentration from 4 to 2 mmol litre^–1for     

Role of PI3-kinase/Akt signalling pathway in renal function and cell proliferation after renal ischaemia/reperfusion injury in mice

BACKGROUND: PI3K/Akt pathway has been shown to play a critical role in the regulation of mitogenic signalling, apoptosis, cell proliferation and survival in a variety of cells and tissues. The aim of the present study was to investigate the role of PI3K/Akt pathway in the renal ischaemia/reperfusion. METHODS: Four experimental groups, sham-operative mice, vehicle-delivered and wortmannin-treated ischaemic/reperfusion injury mice, wortmannin-treated normal mice were designed to examined serum blood urea nitrogen level, renal injury, proliferating cell nuclear antigen protein and Akt phosphorylation status at 30 min, 90 min, 24 h, 48 h of reperfusion after ischaemic treatment. Wortmannin or its vehicle was given intraperitoneally at 4 h before surgery. Blood urea nitrogen was measured, and immunohistochemistry and western blotting were used to detect the components of PI3K/Akt pathway in the ischaemic/reperfusion injury kidney. RESULTS: PI3-kinase inhibitor wortmannin imposes a deleterious effect on serum blood urea nitrogen level, renal function after renal ischaemia/reperfusion injury in mice. The renal cell proliferation increased after ischaemia/reperfusion injury in mouse, which could be inhibited by wortmannin. Phosphorylation of Akt was increased after ischaemia/reperfusion in the mouse kidney, and reduced by wortmannin administration. CONCLUSION: This primary study suggests that PI3-kinase/Akt signalling pathway play an important role in the regulation of the renal repair after ischaemia/reperfusion injury.     

Sevoflurane- and Desflurane-induced human myocardial post-conditioning through Phosphatidylinositol-3-kinase/Akt signalling

Background: The role of phosphatidylinositol-3-kinase (PI3K) in sevoflurane- and desflurane-induced myocardial post-conditioning remains unknown.
Methods: We recorded isometric contraction of isolated human right atrial trabeculae (oxygenated Tyrode's at 34 °C, stimulation frequency 1 Hz). In all groups, a 30-min hypoxic period was followed by a 60-min reoxygenation period. At the onset of reoxygenation, muscles were exposed to 5 min of sevoflurane 1%, 2%, and 3%, and desflurane 3%, 6%, and 9%. In separate groups, sevoflurane 2% and desflurane 6% were administered in the presence of 100 nM wortmannin, a PI3K inhibitor. Recovery of force after the 60-min reoxygenation period was compared between groups (mean ± SD).
Result: As compared with the Control group (49 ± 7% of baseline) PostC by sevoflurane 1%, 2%, and 3% (78 ± 4%, 79 ± 5%, and 85 ± 4% of baseline, respectively) and desflurane 3%, 6%, and 9% (74 ± 5%, 84 ± 4%, and 86 ± 11% of baseline, respectively) enhanced the recovery of force. This effect was abolished in the presence of wortmannin (56 ± 5% of baseline for sevoflurane 2%+wortmannin; 56 ± 3% of baseline for desflurane 6%+wortmannin). Wortmannin alone had no effect on the recovery of force (57 ± 7% of baseline).
Conclusion: In vitro , sevoflurane and desflurane post-conditioned human myocardium against hypoxia through activation of phosphatidylinositol-3-kinase.     

Corresponding minimum alveolar concentrations of isoflurane and isoflurane/nitrous oxide have divergent effects on thalamic nociceptive signalling

BACKGROUND: Suppression of nociceptive signalling in the thalamus is consideredto contribute significantly to the anaesthetic state. Assumingadditivity of anaesthetic mixtures, our study assessed the effectsof corresponding minimum alveolar concentrations (MACs) of isofluraneand isoflurane/nitrous oxide on thalamic nociceptive signalling. METHODS: Nociceptive response activity (elicited by controlled radiantheat stimuli applied to cutaneous receptive fields) of singlethalamic neurons was compared in rats anaesthetized at 1.1 and1.4 MAC isoflurane with that at 1.1 and 1.4 MAC isoflurane/nitrousoxide. RESULTS: Under baseline anaesthesia (0.9 MAC isoflurane), noxious stimulationelicited excitatory responses in all neurons (n = 19). Theseresponses were uniformly suppressed at 1.1 and 1.4 MAC isoflurane.In contrast, at 1.1 and 1.4 MAC isoflurane/nitrous oxide, excitatoryresponses no different to baseline were still present in 64and 37% of the neurons, respectively. CONCLUSIONS: These data demonstrate a pronounced nitrous oxide-induced responsevariability. It appears that, with respect to thalamic transferof nociceptive information, the interaction of isoflurane andnitrous oxide may not be compatible with the concept of additivityand that the antinociceptive potency of nitrous oxide is considerablyless than previously reported.     

Differential effects of halothane and isoflurane on lumbar dorsal horn neuronal windup and excitability

Background. Windup of spinal nociceptive neurones may underlietemporal summation of pain, influencing the minimum alveolarconcentration (MAC) of anaesthetics required to prevent movementto supramaximal stimuli. We hypothesized that halothane andisoflurane would differentially affect windup of dorsal hornneurones. Methods. We recorded 18 nociceptive dorsal horn neurones exhibitingwindup to 1 Hz electrical hindpaw stimuli in rats. Effects of0.8 and 1.2 MAC isoflurane and halothane were recorded in thesame neurones (counterbalanced, crossover design). Windup wascalculated as the total number of C-fibre (100–400 mslatency) plus afterdischarge (400–1000 ms latency) spikes/20stimuli (area under curve, AUC) or absolute windup (C-fibreplus afterdischarge–20xinitial response). Results. Increasing isoflurane from 0.8 to1.2 MAC did not affectAUC, but increased absolute windup from 429 (62) to 618 (84)impulses/20 stimuli (P<0.05) and depressed the initial C-fibreresponse from 14 (3) to 8 (2) impulses (P<0.05). Increasinghalothane from 0.8 to1.2 MAC depressed AUC from 690 (79) to537 (65) impulses/20 stimuli (P<0.05) and the initial responsefrom 18 (2) to 13 (2) impulses (P<0.05), but absolute windupwas not affected. Absolute windup was 117% greater during 1.2MAC isoflurane compared with 1.2 MAC halothane. Conclusions. Windup was significantly greater under isofluranethan halothane anaesthesia at 1.2 MAC, whereas the initial C-fibreresponse was suppressed more by isoflurane. These findings suggestthat these two anaesthetics have mechanistically distinct effectson neuronal windup and excitability.     

The influence of Phosphatidylinositol 3-kinase/Akt Pathway on the Ischemic Injury during Rat Liver Graft Preservation

We aimed to investigate the role of phosphatidylinositol 3 (PI3)-kinase/Akt pathway on ischemic injury. Rat liver grafts were preserved in UW solution with different treatments and were compared by 1-week survival rates and morphological changes with those of the control group. PI3-kinase/Akt was significantly activated at the sites of Thr 308 and Ser 473 in the preserved grafts. Downstream target proteins, glycogen synthase kinase-3beta (GSK-3beta) and caspase-9, were inactivated. However, survival signal transduction from Akt to Bad was blocked by calcium release after activation of PI3-kinase/Akt. Significant activation of caspase-12, -3 and -7 contributed to cell apoptosis and severe ischemic injury was shown after 7 h of preservation by UW solution with insulin. Downregulation of phospho-Akt at Thr 308 and Ser 473 was due to partial inhibition of PI3-kinase/Akt pathway by LY294002. Activation of GSK-3beta and inactivation of caspase-12 and Bad could be found in the LY294002 groups in which the liver grafts showed less ischemic injury. Higher 1-week survival rates in the heparin, LY294002, and glucagon groups confirmed the dysregulation of the pathway. In conclusion, PI3-kinase/Akt pathway was dysregulated and contributed to ischemic injury during preservation. Heparin and LY294002 could improve graft viability by maintaining calcium homeostasis during preservation.     

The mechanism of sevoflurane-induced cardioprotection is independent of the applied ischaemic stimulus in rat trabeculae

Background. Sevoflurane protects the myocardium against ischaemicinjury through protein kinase C (PKC) activation, mitochondrial     

异丙酚预处理对大鼠离体心脏缺血再灌注时心肌线粒体的影响

目的 探讨异丙酚预处理对大鼠离体心脏缺血再灌注时心肌线粒体的影响.方法 成年雄性SD大鼠60只,体重250～300 g,随机分为5组(n=12):对照组(Con组)、缺血再灌注组(I/R)和不同浓度异丙酚组(P1组、P2组、P3组).采用Langendorpf离体心脏灌注模型,用K-H液平衡20 min后,Con组继续用K-H液灌注130 min;I/R组用K-H液灌注40 min,缺血30 min,再灌注60 min;P1组、P2组、P3组于缺血前分别用含50、100、150 μmol/L异丙酚的K-H液灌注10 min,再用K-H液冲洗10 min,该过程总共进行2次为预处理,预处理后各组处理均同I/R组.记录平衡20 min(基础值)、缺血前即刻、再灌注60 min的心率(HR)、左心室舒张末压(LVEDP)、左心室发展压(LVDP)、左心室压力上升及下降速率最大值(±dP/dtmax)、冠脉流量(CF).于再灌注60 min时测定心肌梗死面积以及线粒体电子传递链Ⅰ复合体活性.结果 与Con组比较,再灌注60 min时I/R组LVEDP升高,HR、LVDP、±dP/dtmax、CF均下降,P2组和P3组LVEDP升高,I/R组和P1组心肌梗死面积增大,I/R组、P1组、P2组和P3组线粒体电子传递链Ⅰ复合体活性降低(P＜0.05);与I/R组比较,P2组及P3组再灌注60 min时LVEDP降低,HR、LVDP、±dP/dtmax、CF均升高,P2组及P3组心肌梗死面积减小,P2组和P3组线粒体电子传递链复合体Ⅰ活性升高(P＜0.05).结论 100、150μmol/L异丙酚预处理通过增加心肌线粒体电子传递链复合体Ⅰ的活性,在一定程度上减轻大鼠心肌缺血再灌注损伤.     

磷脂酰肌醇-3-激酶/丝氨酸苏氨酸蛋白激酶/内皮型一氧化氮合酶信号通路在二氮嗪后处理缺血/再灌注大鼠心肌中的作用

目的 研究磷脂酰肌醇-3-激酶/丝氨酸苏氨酸蛋白激酶/内皮型一氧化氮合酶(phosphatidylinositol-3-kinase/protein serine threonine kinase/endothelial nitric oxide synthase,PI3K/Akt/eNOS)信号通路在二氮嚷后处理大鼠在体心肌缺血/再灌注(ischemia/reperfusion,I/R)损伤中的作用. 方法 40只雄性SD大鼠完全随机分为5组,每组8只:假手术组(S组)、I/R组、二氮嗪组(D组)、PI3K抑制剂渥蔓菁霉素组(W组)和二氮嗪+渥蔓菁霉素组(DW组).结扎左冠状动脉前降支30 min、再开放120 min,建立在体心肌I/R损伤模型,S组不结扎.再灌注5 min前,5组依次分别经股静脉输入0.1％二甲基亚砜(dimethyl sulfoxide,DMSO)1 ml/kg、0.1％ DMSO 1 ml/kg、二氮嗪7 mg/kg、渥蔓菁霉素15 μg/kg,DW组于输入二氮嗪前5 min输入渥蔓菁霉素;所有药物均输注15 min.再灌注末,测定血浆心肌肌钙蛋白I(cardiac troponin I,cTnI)浓度,苏木精-伊红(HE)染色观察心肌病理变化,免疫组化分析eNOS的表达情况. 结果 与S组比较,其余4组cTnI显著增高(P＜0.01),心肌明显损伤,eNOS表达增高(P＜0.05或P＜0.01).与I/R组比较,D组和DW组cTnI[(36.5±5.2) μg/L与(44.5±4.5)μg/L vs (64.7±11.1) μg/L]明显降低(P＜0.01),心肌病理改变减轻,eNOS表达增高[(0.515±0.136)％与(0.394±0.100)％ vs (0.241±0.077)％](P＜0.01).与D组比较,DW组cTnI明显增高[(44.5±4.5) μg/L vs (36.5±5.2) μg/L] (P＜0.05),心肌损伤加重,eNOS表达降低[(0.394±0.100)％ vs (0.515±0.136)％] (P＜0.01). 结论 二氮嗪后处理减轻大鼠心肌I/损伤的作用部分与PI3K/Akt/eNOS信号通路激活有关.     

Xenon preconditioning differently regulates p44/42 MAPK (ERK 1/2) and p46/54 MAPK (JNK 1/2 and 3) in vivo

Background. Xenon (Xe) induces preconditioning (PC) of the ratheart in vivo via activation of p38 mitogen-activated proteinkinase (MAPK). The role of ERK 1/2 and JNK 1/2 and 3 in Xe-PChas yet not been determined. Methods. For infarct size measurements, anaesthetized rats weresubjected to 25 min of coronary artery occlusion followed by120 min of reperfusion. Animals received Xe 70% during three5 min periods with and without the ERK inhibitor PD 98059 (1mg kg^–1, PD) or the JNK inhibitor SP 600125 (6 mg kg^–1,SP) (n=10 per group). Additional hearts were excised for westernblot and kinase activity assay: without further treatment, afterthe first, the second and the third period of Xe-PC or at theend of the last washout phase (n=4 each). Results. Infarct size (% of area at risk) was reduced from 46.2(8.1)% to 28.4 (11.3)% after Xe-PC (P<0.01). PD completelyabolished this effect [49.7 (11.4)%, P<0.01 vs Xe-PC]. Theratio of particulate/cytosolic phospho ERK 1/2 was time dependentlyincreased during the PC protocol [ERK 1: 15 min: 2.4 (1.2),25 min: 1.5 (0.3), 35 min: 1.6 (0.7), 45 min: 1.5 (0.5) vs Con1.0 (0.5) and ERK 2: 15 min: 3.3 (1.8), 25 min: 2.0 (1.5), 35min: 1.8 (1.7), 45 min: 0.9 (0.6) vs Con 0.8 (0.4)]. This findingwas confirmed by a non-radioactive MAPK activity assay. In contrastSP had no effect on Xe-PC and the phosphorylation state of JNKwas not influenced by Xe-PC. Conclusion. Besides the p38 MAPK, ERK 1/2 also is a mediatorof Xe-PC. However, JNK is not involved, demonstrating a highlyspecific regulation of different kinases during Xe-PC.