Actions of ketamine and its isomers on contractility and calcium transients in human myocardium.

BACKGROUND: Ketamine has a species-dependent inotropic effect on myocardium. The authors' aim was to investigate the direct inotropic effect and the corresponding intracellular Ca2+ transients of ketamine and its isomers on human myocardium. METHODS: Right auricular myocardial strips obtained during open heart surgery were exposed to increasing concentrations (73 microM, 360 microM, and 730 microM) of racemic ketamine (n = 12), S(+)-ketamine (n = 12), or R(-)-ketamine (n = 11). Isometric force, isotonic shortening, contractility, relaxation, and time to maximal isotonic and isometric force were assessed. Ten muscle strips in each group were loaded with the calcium-sensitive fluorescent dye FURA-2/AM for simultaneous measurements of calcium transients. RESULTS: Compared with the initial control maximal isometric developed force, maximal isotonic shortening amplitude, contractility, and relaxation increased by 12.5-22.4% after perfusion with S(+)-ketamine at the concentration of 73 microM (P < 0.05). In contrast, no changes were seen after addition of 73 microM R(-)-ketamine. The effect of racemic ketamine (73 microM) was between that of the two isomers. At the highest concentration (730 microM) ketamine and its isomers decreased maximal isometric developed force, maximal shortening amplitude, contractility, and relaxation by 26.8-57.4% (P < 0.05), accompanied by a significant decrease of the intracellular calcium transient (by 21.0-32.2%, P < 0.05). CONCLUSIONS: In contrast to R(-)-ketamine, S(+)-ketamine increased isometric force, isotonic shortening, contractility, and relaxation at low concentrations (73 microM) compared with the initial control. At higher concentrations (730 microM) a direct negative inotropic action was observed after perfusion with ketamine and its isomers, which was accompanied by a decreased intracellular Ca2+ transient.     

Combined depressant effects of diltiazem and volatile anesthetics on contractility in isolated ventricular myocardium

Because the volatile anesthetics depress the entry of calcium (Ca) into myocardial cells and also alter release of intracellular Ca stores, additional pharmacologic blockade of Ca entry could potentially enhance anesthetic-induced depression. The depressant effects of the calcium entry blocker diltiazem combined with the volatile anesthetics halothane, enflurane, or isoflurane were investigated in isolated guinea pig papillary muscle. Muscle contractions were studied in normal Tyrode solution after rest and at stimulation rates of 0.1, 0.25, 0.5, 1, 2, and 3 Hz. Anesthetics were studied in the presence of 0.1 and 1 microM diltiazem, which depressed tension to approximately 85 and 55% of control at 2-3 Hz, respectively; depression at the higher concentration was frequency-dependent. Depressant effects of enflurane were determined as previously done for equianesthetic concentrations (approximately 1 and 2 MAC) of halothane and isoflurane. At all stimulation rates, 1.7 and 3.5% enflurane depressed peak tension and dT/dt-max to approximately 73 and 50% of the mean control-recovery value, respectively. After control measurements of contractile characteristics, effects of 0.1 microM diltiazem were determined alone and then with the addition of halothane (0.75 or 1.5%), isoflurane (1.3 or 2.5%), or enflurane (1.7 or 3.5%), respectively. Recovery from anesthetic was then determined in the continued presence of diltiazem. After rest and at rates less than or equal to 0.5 Hz, equianesthetic concentrations of these volatile agents caused similar depression in the presence of diltiazem. At 3 Hz stimulation rate, 1.3% isoflurane caused significantly less contractile depression than did 1.7% enflurane or than 0.75% halothane. At 2-MAC concentrations, differences among the anesthetics were more apparent: 2.5% isoflurane depressed peak tension and dT/dt-max less than did halothane at 1-3 Hz stimulation rates, and depressed dT/dt-max less than 3.5% enflurane at 2-3 Hz. Similar frequency-dependent differences in depression by approximately 2 MAC anesthetics were observed in the presence of 1 microM diltiazem. The patterns of depressant action by the volatile anesthetics were similar to those previously observed in the absence of diltiazem. Furthermore, when the volatile anesthetic depression of contractions was combined with the depression due to diltiazem-induced blockade of Ca entry, the resulting contractile depression did not differ significantly from a prediction that assumed simply additive effects.     

Effects of halothane and isoflurane on isolated human ventricular myocardium

Segments of viable human left ventricular trabeculae were obtained at the time of endocardial resection for intractable ventricular ectopy. Muscle segments which showed suitable and reproducible contractions in 26 mM K Tyrode solution with 1 microM isoproterenol were electrically stimulated after rest, and at frequencies of 0.1, 0.25, 0.5, and 1 Hz. Effects of 0.75% halothane and 1.3% isoflurane on peak tension, maximum rate of tension development (dT/dt-max), and on slow (calcium dependent) action potential (AP) characteristics were studied. Halothane depressed peak tension, dT/dt-max, and slow AP maximum rate of depolarization (Vmax) at all frequencies, and caused a significantly greater depression of peak tension and dT/dt-max at 0.5-1 Hz than after rest and at 0.1-0.25 Hz. Isoflurane did not significantly depress slow AP Vmax, showed no frequency dependent contractile depression, and depressed dT/dt-max less than halothane at 0.5 and 1 Hz. Halothane and isoflurane caused differing depression in the pattern of developed tension. The differential depression by halothane and isoflurane of human ventricular myocardium was similar to that previously observed in isolated animal ventricular tissue.     

Comparative effects of bupivacaine and ropivacaine on intracellular calcium transients and tension in ferret ventricular muscle

BACKGROUND: Recent evidence suggests that ropivacaine exerts markedly less cardiotoxicity compared with bupivacaine; however, the mechanisms are not fully understood at the molecular level. METHODS: Isolated ferret ventricular papillary muscles were microinjected with the Ca-binding photoprotein aequorin, and intracellular Ca transients and tension were simultaneously measured during twitch in the absence and presence of bupivacaine or ropivacaine. RESULTS: Bupivacaine and ropivacaine (10, 30, and 100 microm) reduced peak systolic [Ca]i and tension in a concentration-dependent manner. The effects were significantly greater for bupivacaine, particularly on tension (approximately twofold). The percentage reduction of tension was linearly correlated with that of [Ca]i for both anesthetics, with the slope of the relationship being approximately equal to 1.0 for ropivacaine and approximately equal to 1.3 for bupivacaine (slope difference, P < 0.05), suggesting that the cardiodepressant effect of ropivacaine results predominantly from inhibition of Ca transients, whereas bupivacaine suppresses Ca transients and the reaction beyond Ca transients, i.e., myofibrillar activation, as well. BAY K 8644, a Ca channel opener, abolished the inhibitory effects of ropivacaine on Ca transients and tension, whereas BAY K 8644 only partially inhibited the effects of bupivacaine, particularly the effects on tension. CONCLUSION: The cardiodepressant effect of bupivacaine is approximately twofold greater than that of ropivacaine. Bupivacaine suppresses Ca transients more markedly than does ropivacaine and reduces myofibrillar activation, which may at least in part underlie the greater inhibitory effect of bupivacaine on cardiac contractions. These results suggest that ropivacaine has a more favorable profile as a local anesthetic in the clinical settings.     

Effects of isoflurane and sevoflurane on intracellular calcium and contractility in pressure-overload hypertrophy

BACKGROUND: Depression of myocardial contractility as a result of isoflurane appears to be greater in myocardial hypertrophy, and the cellular basis for this difference in susceptibility is not clear. In this study we examined the effects of isoflurane and sevoflurane on contractility and intracellular calcium in an animal model of pressure-overload hypertrophy. METHODS: Pressure-overload hypertrophy was established in young male ferrets by banding the main pulmonary artery for 1 month and the effects of isoflurane and sevoflurane on contractility and intracellular calcium ([Ca]i) were examined in isolated right ventricular papillary muscles, trabeculae, and myocytes. Intracellular calcium was measured with the bioluminescent photoprotein aequorin in isolated papillary muscles, and also with the fluorescent indicator fluo-3 in isolated ventricular myocytes. In addition, Ca sensitivity was assessed in isolated trabeculae after disruption of the surface membrane with a nonionic detergent (skinned fibers). RESULTS: In the presence of isoflurane and sevoflurane, papillary muscles from banded animals exhibited a greater depression of contractility and isolated ventricular myocytes showed a greater decrease in peak [Ca]i. Furthermore, baseline calcium sensitivity was decreased and the slope of the relationship between [Ca] and force was increased in skinned trabeculae from banded animals. Isoflurane decreased calcium sensitivity in trabeculae from both normal and banded animals. CONCLUSIONS: These results suggest that changes in [Ca]i and altered calcium sensitivity are both responsible for the exaggerated effects of some volatile anesthetics on contractility in pressure-overload hypertrophy.     

17β-雌二醇对大鼠破骨细胞内钙浓度影响的研究

目的探讨雌激素调节破骨细胞活性机制。方法以Ｃｈａｍｂｅｒ方法加以改良,常规体外培养新生Ｗｉｓｔｅｒ大鼠破骨细胞（Ｏｓｔｅｏｃｌａｓｔ,ＯＣ）。镜下观察细胞形态,测定不同浓度１７β－雌二醇（１７βＥ２）有在钙与无钙溶液中对破骨细胞钙浓度（ＯＣ「Ｃａ＾２＋」ｉ）的影响。结果３０ｍｉｎ后ＯＣ贴壁生长,胞浆伸展。２ｈ后细胞形态为多形性,有片状或丝状伪足,常规生存５２ｈ。１７βＥ２使细胞变小,除去１７βＥ２     

Effects of halothane on delayed afterdepolarization and calcium transients in dog ventricular myocytes exposed to isoproterenol

The effects of halothane on isoproterenol-induced delayed after-depolarizations (DADs) were investigated in canine ventricular myocytes. In addition, the effects of halothane on the intracellular free calcium transient were determined in fura-2-loaded myocytes exposed to isoproterenol to explore the mechanisms underlying halothane effects on DADs. Isoproterenol (100 nM) induced DADs and/or undriven action potentials in myocytes stimulated electrically with the use of trains of 10 stimuli delivered at basic drive cycle lengths of 200-1,000 ms. Isoproterenol (100 nM) increased the peak ratio (350/380 nm excitation) of stimulated myocyte calcium transients; furthermore, isoproterenol induced a second spontaneous component in the calcium transients of 62% of treated myocytes (n = 72). Halothane (1.5%, 0.53 mM) significantly decreased the amplitude of isoproterenol-induced DADs (P less than 0.01). Halothane not only reduced the peak ratio of the stimulated calcium transient, but also eliminated the second spontaneous component in myocytes previously exposed to isoproterenol (n = 14). Elevated extracellular calcium concentrations (5 mM) restored the amplitudes of DADs and the second components of the calcium transients in myocytes exposed to isoproterenol and halothane. These data suggest that halothane opposes isoproterenol-induced DADs by altering intracellular calcium stores. The authors' findings do not support a role for DAD-induced triggered activity in the genesis of anesthetic-catecholamine dysrhythmias.     

Acute pulmonary hypertension causes depression of left ventricular contractility and relaxation

BACKGROUND AND OBJECTIVE: The haemodynamic effects of acute pulmonary hypertension can be largely attributed to ventricular interdependence during diastole. However, there is evidence that the two ventricles also interact during systole. The aim of the present study was to examine the effects of acute pulmonary hypertension on both components of left ventricular systole, i.e. contraction and relaxation, using load-independent indices. METHODS: Ten pigs were instrumented with biventricular conductance catheters, a pulmonary artery flow probe and a high-fidelity pulmonary pressure catheter. Haemodynamic measurements were performed in baseline conditions and during stable pulmonary vasoconstriction induced by the thromboxane analogue U46619. Contractility was quantified using the end-systolic pressure-volume and preload recruitable stroke work relationships. The tau-end-systolic pressure relationship was used to assess load-dependency of relaxation. RESULTS: Acute pulmonary hypertension caused a decrease in the slope of the left ventricular preload recruitable stroke work relationship (from 6.64 +/- 1.7 to 5.19 +/- 1.9, mean +/- SD; P < 0.05), a rightward shift of the end-systolic pressure-volume relationship (P < 0.05), and an increase in the slope of the tau-end-systolic pressure relationship (from -0.15 +/- 0.5 to 0.35 +/- 0.17; P < 0.05). The diastolic chamber stiffness constant of both ventricles increased during pulmonary hypertension (P < 0.05). CONCLUSIONS: In the present model, acute pulmonary hypertension impairs left ventricular contractile function and relaxing properties. The present study provides additional evidence that, besides the well-known diastolic ventricular cross talk, systolic ventricular interaction may play a significant role in the haemodynamic consequences of acute pulmonary hypertension.     

Effects of halothane on contraction and intracellular calcium in ventricular myocytes from streptozotocin-induced diabetic rats

Background. Some of the cellular targets affected by volatileanaesthetics (e.g. halothane) which contribute to the negativeinotropic effects of these agents are also affected during theprogression of diabetic cardiomyopathy. A previous report suggestedthat halothane inhibited contraction to a lesser extent in papillarymuscle from diabetic animals and so the aim of this study wasto investigate possible mechanisms underlying this effect. Methods. Contractility and cytosolic calcium ion (Ca²⁺) transientswere measured (fura-2) in ventricular myocytes isolated fromcontrol and streptozotocin (STZ)-induced diabetic rats in theabsence and presence of halothane 0.6 mmol litre^–1 at1 Hz stimulation. Sarcoplasmic reticulum (SR) Ca²⁺ content wasassessed by rapid application of caffeine. All experiments werecarried out at 36–37°C. Results. The amplitude of shortening, the electrically evokedCa²⁺ transient, SR Ca²⁺ content and myofilament Ca²⁺ sensitivity,though not altered by STZ treatment, were significantly reducedby halothane to a similar extent in control and STZ myocytes.The time course of contraction and Ca²⁺ transient were prolongedin myocytes from STZ-treated rats compared with controls butthis was not altered further by halothane. STZ treatment appearedto reduce Ca²⁺ efflux from the cell, an effect reversed by halothane. Conclusions. In contrast to a previous report, we could findno evidence of amelioration of the negative inotropic effectof halothane in myocytes from the STZ-induced diabetic rat.Contractility, the cytosolic Ca²⁺ transient, SR Ca²⁺ contentand myofilament Ca²⁺ sensitivity were qualitatively similarin control and STZ myocytes and were all depressed to the sameextent by halothane. Br J Anaesth 2004; 92: 246–53     

Effect of partial outflow obstruction on rat detrusor contractility and intracellular free calcium concentration

Partial outlet obstruction induces significant alteration in detrusor contractility. A mild obstruction can result in increased contractile force, whereas severe obstruction results in marked contractile dysfunction. The cellular mechanisms mediating these alterations in the contractile response are presently not known. In the current study, we have investigated the effect of both mild and severe partial outlet obstruction on detrusor contractility and correlated the contractile response to field stimulation, bethanechol, adenosine triphosphate (ATP), and KCl with the level of intracellular free calcium using FURA-2 fluorescence. Our results are as follows. Severe obstruction induced a significantly greater increase in bladder weight than mild obstruction. In general, mild outlet obstruction induced an increase in the contractile responses to field stimulation, bethanechol, ATP, and KCl, whereas severe outlet obstruction induced a decrease to field stimulation and ATP. In general, the stimulated increase in intracellular free calcium paralleled the contractile response. The results indicate that the alterations in the contractile response to field stimulation and pharmacological stimulation induced by partial outlet obstruction may be mediated by altered calcium translocation and intracellular release. © 1994 Wiley-Liss, Inc.     

Metformin but not glyburide prevents high glucose-induced abnormalities in relaxation and intracellular Ca2+ transients in adult rat ventricular myocytes.

We have recently demonstrated that adult rat ventricular myocytes maintained in a high glucose (HG) culture medium exhibit abnormalities in excitation-contraction coupling similar to myocytes from diabetic rats. Metformin, an insulin-sensitizing biguanide, enhances peripheral insulin action and lowers blood pressure in hyperinsulinemic animals, but its direct impact on cardiac function is not fully understood. To examine the role of metformin on HG-induced cardiac dysfunction at the cellular level, normal adult ventricular myocytes were cultured for 1 day in a serum-free insulin-containing medium with either normal glucose (5.5 mmol/l glucose) or HG (25.5 mmol/l glucose) in the presence or absence of metformin or the sulfonylurea glyburide. Mechanical properties were evaluated using a high-speed video-edge detection system, and intracellular Ca2+ transients were recorded in fura-2-loaded myocytes. As previously reported, culturing myocytes in HG depresses peak shortening, prolongs time to 90% relengthening, and slows Ca2+ transient decay. Culturing cells with metformin (50 micromol/l) prevented the HG-induced abnormalities in relaxation without ameliorating depressed peak-shortening amplitudes. Incubation of the cells with metformin also prevented slower intracellular Ca2+ clearing induced by HG. However, the HG-induced relaxation defects were not improved by glyburide (50-300 micromol/l). Interestingly, metformin also improved HG-induced relaxation abnormalities in the absence of insulin, whereas it failed to protect against HG in the presence of the tyrosine kinase inhibitor genistein (50 micromol/l). These data demonstrate that, unlike glyburide, metformin provides cardioprotection against HG-induced abnormalities in myocyte relaxation, perhaps through tyrosine kinase-dependent changes in intracellular Ca2+ handling, independent of its insulin sensitizing action.     

Influence of mild metabolic acidosis on cardiac contractility and isoprenaline response in isolated ovine myocardium

The postoperative course after major surgical procedures such as cardiothoracic operations is often accompanied by acute metabolic abnormalities due to large volume and temperature shifts. In general, those intervention-induced trauma might cause the use of catecholamines to stabilize hemodynamics. Within the cardiac community, there are still controversial discussions about standardized medical therapy to treat postoperative acidosis, for example, buffering versus nonbuffering for improving catecholaminergic response of myocardial contractility. The aim of this study was to investigate the influence of mild (and thus clinically relevant) acidosis on myocardial contractility and catecholamine response in explanted trabeculae of ovine hearts. Intact trabeculae (n = 24) were isolated from the right ventricle of healthy sheep hearts. Two different groups (group 1: pH = 7.40, n = 9 and group 2: pH = 7.20, n = 13) were investigated, and force amplitudes were measured at frequencies between 30 and 180 beats per minute and increasing catecholamine concentrations (isoprenaline 0-3 × 10(-6) mM). Force-frequency relation experiments in the presence of a physiological and/or mild acidotic pH solution showed no significant differences. Mean force amplitudes normalized to the lowest frequency showing no significant differences in force development between 0.5 and 3 Hz (n = 9 vs. 13, P = n.s.) (0.5 Hz absolute values 3.1 ± 2.6 for pH = 7.40 vs. 3.8 ± 2.6 mN/mm(2) for pH = 7.20, P = n.s.). Moreover, there was no significant difference in relaxation kinetics between the two groups. Furthermore, the experiments showed similar catecholamine responses in both groups. Force amplitudes normalized to baseline and maximum force showed no significant differences in force development between baseline and maximum isoprenaline concentrations (n = 6 vs. 9, P = n.s.) (baseline absolute values 4.3 ± 4.0 for pH = 7.40 vs. 3.9 ± 1.2 mN/mm(2) for pH = 7.20, P = n.s.). Additionally, relaxation kinetics did not show differences after catecholamine stimulation. The presented experiments revealed no significant negative inotropic effects on isometrically contracting ovine trabeculae with mild metabolic acidosis (pH = 7.2) compared with physiological pH (7.4). Additionally, similar catecholamine responses were seen in both groups. Further investigations (e.g., in vivo and/or in failing hearts with reduced compensatory reserves) will be necessary to examine optimal medical treatment for metabolic abnormalities after cardiac surgery.     

血管紧张素转化酶抑制剂对心衰大鼠心肌收缩特性及钙调控蛋白表达的影响

目的观察血管紧张素转化酶抑制剂（ACEI）对心衰大鼠心肌收缩特性的影响，探讨与心肌细胞钙调控蛋白NCX1、SERCA2、PLB表达水平的关系。方法缩窄Wistar大鼠腹主动脉制作心衰模型，随机分成培哚普利治疗组（CHF-T，n＝16）、心衰对照组（CHF-C，n＝16）和假手术组（PS，n＝10）。12周后，进行心肌收缩功能测定和心肌钙调控蛋白的免疫荧光半定量分析。结果CHF-C组的左室舒张未期压力（LVEDP）高于PS组、＋dp／dt和-dp／dt则较PS组为低（P均〈0．05），ACE抑制剂治疗的CHF-T组则明显减轻上述改变（尸均〈0．05）；在1．0Hz电刺激下，CHF-T组心肌细胞缩短分数Fs（％）与CHF-C组比较，有明显改善（10．89±1．18、7．51±1．15，P〈0．01）。NCX1、SERCA2的蛋白表达量在CHF-T、CHF．C和PS3组间差异有统计学意义（NCX1：2988．79±149．37、3289．03±153．63、2780．61±136．57（P〈0．01）；SERCA2：4380．82±237．15、4092．05±185．76、4703．81±250．35，P〈0．01），其中CHF-C组与PS组比较，NCX1表达明显增高、SERCA2明显降低（P〈0．01）；CHF—T组与CHF—C组比较，其NCX1表达显著降低（P〈0．01）、SERCA2有所增高（P〈0．05），但均未恢复至假手术组水平（P〈0．05）。而PLB在各组间的表达差异无统计学意义（P〉0．05）。结论ACEI的长程干预可以减缓心力衰竭时心肌钙调控蛋白的变化，保护心肌的收缩特性。     

瑞芬太尼对电刺激诱导大鼠心室肌细胞钙瞬变的影响

目的观察不同浓度瑞芬太尼对电刺激诱导的大鼠心室肌细胞钙瞬变的影响。方法雄性SD大鼠，体重190—210g，分离单个心室肌细胞，在细胞逐步复钙后行细胞指标剂的负载，采用钙敏感荧光探针Fluo-2／AM结合激光扫描共聚焦显微镜测定胞浆游离钙浓度（[Ca^2＋]i），分别用含0．1、0．3、1、3、10、30、100、300、1000ng／ml瑞芬太尼的Kreb’8液灌流细胞，每个浓度8个细胞，以波长340／380nm时荧光比值反映[Ca^2＋]i），用0．2Hz的电流刺激细胞，产生的[Ca^2＋]i峰值即为电刺激激发的瞬时[Ca^2＋]i，给予瑞芬太尼后瞬时[Ca^2＋]i与基础值的比值表示钙瞬变振幅，绘出量．效关系曲线和100ng／ml瑞芬太尼的时．效关系曲线。结果瑞芬太尼剂量依赖性抑制钙瞬变，Sigmoidal方程为Y=78．49＋25．31／[1＋10^（-6.41-x）]（P〈0．01），半数有效浓度为0．4ng／ml，R^2为0．9833；100ng／ml瑞芬太尼时间依赖性抑制钙瞬变，Sigmoidal方程为Y=68．5＋45．7／[1＋10^（-0.358-x）]（P〈0．01），达半数最大效应的时间为2．3min，R^2为0．937。结论瑞芬太尼对电刺激诱发的大鼠心室细胞钙瞬变产生剂量和时间依赖性抑制。     

Effects of etomidate on whole-cell and single L-type calcium channel currents in guineapig isolated ventricular myocytes

We have investigated the effects of etomidate 4.4 µmollitre^–1, 1.0 mg litre^–1 and 27.4 µmol litre^–1,6.25 mg litre^–1 on whole-cell and single L-type calciumchannel currents in myocytes from guineapig ventricles. Forwhole-cell recordings, the cells were voltage-clamped and stepdepolarizations were applied from holding potential of –40mV to various potentials to elicit L-type calcium currents.Peak calcium currents were decreased significantly by both lowand high concentrations of etomidate. Ethanol in the same concentrationwith the highest etomidate solution (1.1 mmol litre^–1)had no significant effect on calcium currents. When single calciumchannel activity was investigated, the high concentration ofetomidate significantly decreased the open probability of thechannel with little or no effect on channel conductance. Meanclosed time was increased significantly, caused apparently byprolongation of the slower of two exponential components fittedto histograms of the closed times. The mean open time was virtuallyunaffected. The low concentration of etomidate did not significantlyaffect single channel kinetics. These results showed that etomidatedecreased L-type calcium current by altering the kinetics ofthe channel to favour the closed state without any significantchange in conductance. However, compared with other anaestheticswhich were investigated previously in our laboratory, the overalleffect on calcium current appeared to be small.     

利多卡因和罗哌卡因对孕大鼠离体子宫平滑肌收缩功能的影响

目的观察碳酸利多卡因、盐酸利多卡因和甲磺酸罗哌卡因和盐酸罗哌卡因对孕大鼠离体子宫平滑肌收缩功能的影响。方法分离孕18～21 d SD大鼠的子宫平滑肌,制备成子宫肌条,采用累积给药法,用Medlab V5．5生物信号采集处理系统记录不同浓度(10-6、3×10-6、10-5、3×10-5、10-4、3×10-4mol／L)碳酸利多卡因、盐酸利多卡因和甲磺酸罗哌卡因与盐酸罗哌卡因对子宫平滑肌收缩力和收缩频率的影响。结果与基础值比较,3×10-4mol／L碳酸利多卡因使子宫平滑肌收缩力降低,10-4-3×10-4mol／L盐酸利多卡因、甲磺酸罗哌卡因和盐酸罗哌卡因使子宫平滑肌收缩力降低,3×10-4mol／L甲磺酸罗哌卡因和盐酸罗哌卡因使子宫平滑肌收缩频率降低(P<0．05),不同浓度盐酸利多卡因和碳酸利多卡因对子宫平滑肌收缩频率无影响;3×10-4mol／L甲磺酸罗哌卡因、盐酸罗哌卡因对子宫平滑肌收缩功能的抑制作用强于利多卡因。结论3×10-4mol/L碳酸利多卡因、盐酸利多卡因和甲磺酸罗哌卡因、盐酸罗哌卡因可抑制孕大鼠子宫平滑肌的收缩功能,等浓度罗哌卡因的抑制作用较利多卡因强。     

Effect of bupivacaine on the isolated rabbit heart: developmental aspect on ventricular conduction and contractility

BACKGROUND: Newborns and infants seem to be at greater risk of bupivacaine cardiotoxicity than adults do. Few experiments have studied the effects of local anesthetics on myocardium associated with developmental changes, and their conclusions are conflicting. The authors compared the effects of bupivacaine on an isolated heart preparation in newborn and adult rabbits. METHODS: The authors used a constant-flow, nonrecirculating Langendorff preparation paced atrially. Adult and newborn rabbit hearts were exposed to step-increasing concentrations of bupivacaine. For each concentration, heart rate was modified with pacing from 180 to 360 beats/min by increments of 30 beats/min. QRS complex duration (index of ventricular conduction) and the first derivative of left ventricular pressure (index of contractility) were measured. The two groups were compared using an Emax model. RESULTS: In newborn and adult rabbits, QRS complex duration increased with increasing bupivacaine concentration. No difference was observed between neonatal and adult hearts. Contractility decreased with increasing bupivacaine concentration. Newborn rabbits were approximately three times more sensitive than adult rabbits to the effects of bupivacaine. However, the concentration leading to 50% decrease in the first derivative of left ventricular pressure was much higher than the concentration leading to half maximum increase in QRS complex duration. CONCLUSIONS: In conclusion, using a whole organ preparation, the authors demonstrated that bupivacaine induces similar impairment in ventricular conduction in newborn and adult rabbits. In particular, the tonic and the phasic blocks were of similar intensity in both groups. Conversely, the effect of bupivacaine on contractility was markedly higher in newborn rabbits than in adult rabbits. Also, contractility was less impaired than ventricular conduction in both groups.     

右美托咪啶预处理对大鼠离体心脏缺血再灌注损伤的影响

目的 评价右美托咪啶预处理对大鼠离体心脏缺血再灌注损伤的影响.方法 健康清洁级雄性Wistar大鼠24只,体重230～ 260 g,制备离体Langendorff心脏灌注模型后,采用随机数字表法,将离体心脏随机分为3组(n=8):缺血再灌注组(I/R组)、右美托咪啶Ⅰ组(DI组)、右美托咪啶Ⅱ组(DⅡ组).各组均先用K-H液平衡灌注10 min后,I/R组用K-H液继续灌注30 min,D I组和DⅡ组分别用含有0.23.、2.30ng/ml右美托咪啶的K-H液继续灌注20 min,再用K-H液冲洗10 min.各组心脏均缺血30 min,K-H液再灌注120 min.于平衡灌注末、再灌注5、30、60和120min时收集冠脉流出液,测定肌酸激酶(CK)和乳酸脱氢酶(LDH)活性.再灌注末取心肌组织,测定SOD活性及MDA含量.结果 与I/R组比较DⅠ组和DⅡ组冠脉流出液CK、LDH活性、心肌组织MDA含量降低,心肌组织SOD活性升高(P＜0.05);与DI组比较,DⅡ组冠脉流出液CK、LDH活性、心肌组织MDA含量降低,心肌组织SOD活性升高(P＜0.05).结论 右美托咪啶预处理可减轻大鼠心肌缺血再灌注损伤,且与浓度有关.