Comparison of halothane, enflurane, and isoflurane with nitrous oxide on contractility and oxygen supply and demand in isolated hearts.

The authors' aim was to examine direct cardiac responses to isoflurane, enflurane and halothane, as altered during mild hypoxia by the substitution of nitrogen (N2) for oxygen (O2), and additionally by the substitution of nitrous oxide (N2O) for N2. Heart rate, atrioventricular conduction time, left ventricular pressure (LVP), peak positive and negative derivatives of LVP (dLVP/dtmax), coronary flow, O2 delivery (DO2), percent O2 extraction, and myocardial O2 consumption (MVo2) were examined in 47 isolated guinea pig hearts. Changes in the ratio of DO2 to MVO2 indicated the relationship of autoregulation of coronary flow to myocardial O2 utilization. Each heart was first exposed to 96% O2 and then randomly exposed to 48% N2 and 48% N2O alone and with three equivalent concentrations of one of three volatile anesthetics: isoflurane (n = 15), halothane (n = 16), or enflurane (n = 16). Results were as follows: 1) N2 alone significantly decreased LVP, +dLVP/dtmax and -dLVP/dtmax, DO2 and MVO2; increased coronary flow; and produced no change in heart rate, atrioventricular conduction time, percent O2 extraction, or the DO2/MVO2 ratio. 2) Compared to N2, N2O alone only produced additional significant decreases in LVP and +dLVP/dtmax. 3) In the presence of N2 or N2O, each volatile anesthetic caused significant stepwise decreases in heart rate, LVP, +dLVP/dtmax and -dLVP/dtmax, MVO2, and percent O2 extraction; no additional change in coronary flow or DO2; and a stepwise increase in the DO2/MVO2 ratio. The effects of halothane and enflurane were generally greater than those of isoflurane. 4) Each volatile anesthetic caused an additive, parallel depression of LVP and percent O2 extraction as a function of MAC with N2O compared to N2. This study demonstrates that the direct negative inotropic effects of halothane and enflurane are more pronounced than those of isoflurane and are accompanied by a greater reduction in O2 utilization by halothane and enflurane than by isoflurane in the presence of mild hypoxia alone or with the addition of N2O. The study also demonstrates that N2O accentuates the negative inotropic effects of volatile anesthetics during reduced O2.     

Inotropic Effects of Propofol, Thiopental, Midazolam, Etomidate, and Ketamine on Isolated Human Atrial Muscle

Background: Cardiovascular instability after intravenous induction of anesthesia may be explained partly by direct negative inotropic effects. The direct inotropic influence of etomidate, ketamine, midazolam, propofol, and thiopental on the contractility of isolated human atrial tissue was determined. Effective concentrations were compared with those reported clinically.

Methods: Atrial tissue was obtained from 16 patients undergoing coronary bypass surgery. Each fragment was divided into three strips, and one anesthetic was tested per strip in increasing concentrations (10 sup -6 to 10 sup -2 M). Strips were stimulated at 0.5 Hz, and maximum isometric force was measured. Induction agents were studied in two groups, group 1 (n = 7) containing thiopental, midazolam, and propofol, and group 2 (n = 9) consisting of etomidate, ketamine, and propofol.

Results: The tested anesthetics caused a concentration-dependent depression of contractility resulting in complete cessation of contractions at the highest concentrations. The IC50 S (mean +/-SEM; micro Meter) for inhibition of the contractility were: thiopental 43+/-7.6, propofol 235+/-48 (group 1), and 246+/-42 (group 2), midazolam 145+/-54, etomidate 133 +/-13, and ketamine 303+/-54.     

Nonuniform behavior of intravenous anesthetics on postischemic adhesion of neutrophils in the guinea pig heart

Adhesion of polymorphonuclear neutrophils (PMN) to the coronary endothelium is a crucial step in the development of ischemic myocardial injury. We tested the possible effects of six widely used IV anesthetics on non- and postischemic coronary adhesion of PMN in isolated perfused guinea pig hearts. Hearts (n = 5-11/group) were perfused under conditions of constant coronary flow. After 15 min global warm ischemia, PMN (10(6)) were infused in the second minute of reperfusion. The number of cells reemerging in the coronary effluent within 2 min was expressed as a percentage of the total number of administered PMN. Anesthetics were given 20 min before ischemia and during reperfusion. In addition, the ability of the drugs to influence the oxidative burst reaction of PMN was assessed by measuring luminol-enhanced chemiluminescence in response to 0.1 microM N-formyl-L-methionyl-L-leucyl-L-phenylalanine. Under nonischemic conditions, 26.3% +/- 0.5% of the injected PMN did not acutely reemerge from the coronary system. Subjecting the hearts to ischemia augmented retention to 40.0% +/- 1.6% (P < 0.05). This postischemic stimulation of adhesion was fully prevented by ketamine (10 microM: 22.8% +/- 1.6%, 20 microM: 26.6% +/- 0.7%), thiopental (25 microM: 24.0% +/- 1.7%, 50 microM: 24.0% +/- 1.4%), and midazolam (1.5 microM: 29.0% +/- 0.9%, 3 microM: 26.4% +/- 1.4%). Propofol also inhibited the augmented postischemic retention at 25 microM (28.7% +/- 2.4%). However, 50 microM propofol, etomidate (0.5 and 1 microM), and fentanyl (1 microM) all had no effect. Only thiopental reduced the nonischemic adhesion value (14.0% +/- 3.7%). This may be linked to the direct antioxidative action of thiopental (50% reduction in oxidative burst activity). Whereas ketamine, midazolam, and propofol did not significantly influence oxidant production by PMN, etomidate and the lipid solvent Intralipid enhanced the burst reaction. This activating effect of the lipid component could explain the biphasic behavior of propofol emulsion. Despite some possible differences in efficacy, several IV anesthetics may protect the heart from PMN-mediated reperfusion injury. Implications: Ketamine, thiopental, and midazolam, but not etomodate or fentanyl, reduce postischemic adhesion of neutrophils in the coronary system of isolated perfused guinea pig hearts, suggesting a role in mitigating myocardial reperfusion injury.     

Changes in the auditory evoked potentials index by induction doses of four different intravenous anesthetics

BACKGROUND: Many studies have investigated the electroencephalographic changes during the induction and maintenance of anesthesia. However, no comparative studies have been performed on the effects of intravenous anesthetics on the auditory evoked potentials index (AAI). The present study was performed to compare the changes in AAI caused by induction doses of thiopental, propofol, midazolam and ketamine. METHODS: Eighty females, aged 30-70 years, referred for mastectomy, had anesthesia induced with thiopental 4 mg/kg, propofol 2 mg/kg, midazolam 0.1 mg/kg or ketamine 1 mg/kg (each 20 patients). The response to verbal command and the AAI were measured every minute for 5 min. RESULTS: The AAI decreased to less than 40 within 1 min with thiopental and propofol. The AAI increased after 3 min with thiopental, but remained low with propofol. The AAI gradually decreased to less than 40 within 4 min with midazolam, but was higher than the AAI with propofol or thiopental. The AAI increased significantly with ketamine. The AAIs at the loss of verbal command were 19 +/- 7 with thiopental, 21 +/- 8 with propofol, 31 +/- 10 with midazolam and 92 +/- 2 with ketamine. CONCLUSION: The AAI correlated with changes in hypnotic level, as measured by the response to verbal command, with induction doses of thiopental, propofol and midazolam, but not with ketamine. The AAI decreased to lower levels with propofol and thiopental than with midazolam at the induction of anesthesia.     

Differential effects of intravenous anesthetics on ciliary motility in cultured rat tracheal epithelial cells

PURPOSE: It has been shown that airway ciliary function is impaired by several anesthetic or sedative drugs, which may predispose anesthetized or intensive care patients to respiratory complications, such as hypoxemia, atelectasis and pulmonary infection. We studied the effects of midazolam, propofol, dexmedetomidine, ketamine, fentanyl, thiopental and pentobarbital on ciliary beat frequency (CBF) in isolated and cultured rat tracheal epithelial (RTE) cells, to investigate their direct CBF action removing influences of non-epithelial cells. METHODS: Rat tracheal epithelial cells were purely isolated from tracheas of adult male Sprague-Dawley rats. After 14 to 21 days of culture, the images of motile cilia were videotaped using a phase-contrast microscope. Baseline CBF and CBF 30 or 50 min after administration of vehicle or one of the above agents were computer-analyzed. RESULTS: Midazolam (0.3-10 microM), propofol (1-100 microM), dexmedetomidine (1-100 nM), fentanyl (0.1-10 nM) and thiopental (30-300 microM) had no effect on CBF. Ketamine at a supraclinical dose (1000 microM) increased CBF (22 +/- 13, mean +/- standard deviation, % increase from baseline; baseline = 100%) significantly (P < 0.01). Fentanyl at a high clinical dose (100 nM) increased CBF significantly (10 +/- 9%). Pentobarbital decreased CBF dose-dependently (100 microM, -2 +/- 6%; 300 microM, -14 +/- 18%; 1000 microM, -75 +/- 5%) and reversibly (P < 0.01). CONCLUSION: These results show that midazolam, propofol, dexmedetomidine and thiopental have no direct action on CBF in isolated RTE cells, whereas high doses of ketamine and fentanyl have direct ciliostimulatory actions and pentobarbital has a direct cilioinhibitory action.     

Midazolam and ketamine inhibit glutamate release via a cloned human brain glutamate transporter

PURPOSE: In cerebral ischemia/anoxia, the glutamate transporter runs in reverse and releases glutamate into the extracellular space, causing irreversible neuronal damage. Intravenous anesthetics attenuate overall glutamate release and prevent neuronal injury during anoxia/ischemia, but their effect on the glutamate transporter is variable. METHODS: A human glial glutamate transporter (hGLT-I) cDNA was isolated by screening a human cerebral cortical library. Cloned cDNA was transfected in Chinese hamster ovary cells. The effect of the intravenous anesthetics midazolam (0.3 to 30 microM), ketamine (10 to 100 microM), thiopental (30 to 300 microM), and propofol (3 to 30 microM) on reversed uptake of L-glutamate via hGLT-I was examined by whole-cell patch-clamp. RESULTS: Midazolam at a concentration 3 microM reduced outward currents arising from reversed L-glutamate uptake via hGLT-I in a concentration-dependent manner. While, ketamine at 100 microM attenuated the same outward currents, to 53.3+/-11.4% of those seen in controls without anesthetics (P<0.05, n=5). In contrast, neither thiopental nor propofol showed effects on outward currents mediated by reversed operation of hGLT-I. CONCLUSIONS: These results suggest that midazolam and ketamine, but not thiopental and propofol, have a capacity to inhibit glutamate release via GLT- I directly.     

Differential Effects of Etomidate, Propofol, and Midazolam on Calcium and Potassium Channel Currents in Canine Myocardial Cells

Background: Intravenous anesthetics etomidate, propofol, and midazolam produce negative inotropic effects of various degrees. The mechanism underlying these differences is largely unknown.

Methods: The effects of intravenous anesthetics on L-type Calcium sup 2+, transient outward and inward-rectifier Potassium sup + channel currents (ICa, IKto, and IK1) were compared in canine ventricular cells using the whole-cell voltage-clamp technique. ICa and IK were elicited by progressively depolarizing cells from -40 to +40 mV, and from -90 to +60 mV, respectively. The peak amplitude and time-dependent inactivation rate of ICa and IK were measured before, during, and after the administration of equimolar concentrations (5, 30, or 60 micro Meter) of etomidate, propofol, or midazolam.

Results: Exposure to etomidate, propofol, and midazolam produced a concentration-dependent inhibition of ICa. Midazolam was the most potent intravenous anesthetic; at 60 micro Meter, etomidate, propofol, and midazolam decreased peak ICa by 16 +/- 4% (mean +/- SEM), 33 +/- 5%, and 47 +/- 5%, respectively. Etomidate, propofol, and midazolam given in a 60-micro Meter concentration decreased IKto by 8 +/- 3%, 9 +/- 2%, and 23 +/- 3%, respectively. IK1 was decreased by 60 micro meter etomidate and midazolam by 20 +/- 6% and 14% +/- 5%, respectively. Propofol had no effect on IK1.     

Hemodynamic action profile of propofol in comparison with midazolam. A study in coronary surgical patients

Propofol, a rapid and short-acting i.v. anesthetic, was associated with the risk of anaphylactic reactions in its original cremophor-EL formulation. It has been reformulated in a soybean emulsion with satisfactory anesthetic properties. A former study of hemodynamic changes after i.v. induction with propofol, thiopental, methohexital, etomidate, and midazolam in patients with coronary artery disease demonstrated that in comparison to other induction agents propofol depressed systolic and diastolic arterial pressures more severely, compromising coronary perfusion. In the present investigation left ventricular parameters as well as hemodynamic effects during extracorporeal circulation (ECC) were studied in comparison to midazolam during opiate analgesia. Methods. Hemodynamic effects of 2 mg/kg body weight propofol as compared to 0.15 mg/kg midazolam were studied in 34 patients during coronary artery surgery before cannulation of the large vessels (measurement of left ventricular parameters) or during ECC (measurement of arterial perfusion pressure and oxygenator volume). Results (see Table 1, Figs. 1 and 2). Propofol decreased systolic and diastolic pressures (-27%, -22%) more than midazolam (-10%, -9%). Cardiac index and stroke volume index were diminished following both drugs (propofol: -14%, -9%; midazolam: -15%, -11%); total systemic resistance was reduced significantly by propofol (-22%). Dp/dtmax was compromised more markedly by propofol (-24%) than by midazolam (-18%), but there was no significant difference.(ABSTRACT TRUNCATED AT 250 WORDS)     

Comparison of the Effects of Etomidate, Propofol, and Thiopental on Respiratory Resistance after Tracheal Intubation

Background: Tracheal intubation frequently results in reversible bronchoconstriction. Propofol has been reported to minimize this response in healthy patients and in asthma patients, but may be unsuitable for hemodynamically unstable patients for whom etomidate may be preferable. The current study examined respiratory resistance after tracheal intubation after induction with either thiopental, etomidate, or propofol. A supratherapeutic dose of etomidate was used to test the hypothesis that the bronchoconstrictive response could be minimized by deep intravenous anesthesia.

Methods: Seventy-seven studies were conducted in 75 patients. Anesthesia was induced with either 2.5 mg/kg propofol, 0.4 mg/kg etomidate, or 5 mg/kg thiopental. Respiratory resistance was measured at 2 min after induction.

Results: Respiratory resistance at 2 min was 8.1+/-3.4 cmH sub 2 O *symbol* l sup -1 *symbol* s (mean+/-SD) for patients receiving propofol versus 11.3+/-5.3 for patients receiving etomidate and 12.3+/-7.9 for patients receiving thiopental (P less than or equal to 0.05 for propofol vs. either etomidate or thiopental).     

Effects of Intravenous Anesthetics on Atrial Wavelength and Atrioventricular Nodal Conduction in Guinea Pig Heart: Potential Antidysrhythmic Properties and Clinical Implications

Background: Supraventricular tachydysrhythmias such as atrial fibrillation frequently complicate the perioperative period. Two electrophysiologic factors critical to the pathogenesis of supraventricular tachydysrhythmias are: 1) atrial wavelength, the product of atrial conduction velocity (CV) and effective refractory period (ERP), and 2) atrioventricular nodal conduction. Modulation of these factors by drugs has important clinical ramifications. The authors studied the effects of propofol, thiopental, and ketamine on atrial wavelength and atrioventricular nodal function in guinea pig isolated atrial trabeculae and hearts, respectively.

Methods: Electrocardiogram recordings in superfused atrial tissue were obtained using hanging microelectrodes. A stimulating and two recording electrodes were placed on a single atrial trabecula, and the interelectrode distance was measured. Atrial ERP determinations were made using a premature stimulus protocol. The time (t) required for a propagated impulse to traverse the interelectrode distance (d) was measured. Conduction velocity was calculated as d/t. Langendorff-perfused guinea pig hearts were instrumented for low atrial pacing (cycle length = 300 ms) and for measurements of stimulus-to-His bundle interval, an index of atrioventricular nodal conduction. To investigate the frequency-dependent behavior of the atrioventricular node, computer-based measurements were made of Wenckebach cycle length (WCL) and atrioventricular nodal ERP.

Results: Thiopental significantly prolonged atrial ERP in a concentration-dependent manner, whereas propofol and ketamine had no significant effect on atrial refractoriness. In contrast, ketamine caused a dose-dependent decrease in atrial CV, but propofol and thiopental had no significant effect on CV. Therefore, thiopental, ketamine, and propofol caused an increase, a decrease, and no change, respectively, in atrial wavelength. All anesthetics caused a concentration-dependent prolongation of the stimulus-to-His bundle interval, atrioventricular nodal ERP, and WCL. However, on an equimolar basis, significant differences in potencies were found. The concentrations of drug that caused a 20% increase in ERP (ERP20) and WCL (WCL20) for propofol, thiopental, and ketamine were 14+/-2 micro Meter, 26+/-3 micro Meter, and 62 +/-11 micro Meter, and 17+/-2 micro Meter, 50+/- 1 micro Meter, and 123+/-19 micro Meter (mean+/-SEM), respectively. Therefore, the rank order of potency for frequency-dependent atrioventricular nodal effects is propofol > thiopental > ketamine.     

四种常用静脉麻醉药对老年病人血液动力学影响的比较

目的 探讨脑电双频指数(BIS)为50时，硫喷妥钠、丙泊酚、咪唑安定、依托咪酯用于老年病人全麻诱导的剂量及其对血液动力学的影响。方法 65岁以上的老年病人48例，随机分为四组：硫喷妥钠组，丙泊酚组，咪唑安定组，依托咪酯组。四组均缓慢静注，并且用HXD-1型脑电监测仪测量每例病人的BIS。当BIS逐渐下降至50时停止静注，分别于注药前、注药后1、3、5、10min用Rheo Cardio Monitor连续非创伤性血液动力监测仪记录和计算出血液动力学有关参数。结果 BP下降以丙泊酚组为显著。丙泊酚组和硫喷妥钠组的PEP/LVEF比值明显增加，但丙泊酚组＞硫喷妥钠组。除依托咪酯组以外其他各组的每搏指数(SD、心脏指数(CI)、射血速率(EV)和每搏功(LVP)均有不同程度的降低，但以丙泊酚组为显著。依托咪酯组体循环血管阻力(SVR)无明显变化，硫喷妥钠组和咪唑安定组均有不同程度的升高，以咪唑安定组为显著，丙泊酚组明显下降。舒张末容量(EDV)咪唑安定组明显下降，其他各组无明显变化。结论 四种静脉麻醉药对老年病人血液动力学的影响由大到小依次为丙泊酚＞咪唑安定＞硫喷妥钠＞依托咪酯。BIS为50时，老年病人各静脉麻醉药的等效剂量为硫喷妥钠4mg／kg、丙泊酚1．2mg／kg、咪唑安定0．16mg／kg、依托咪酯0．34mg／kg。对于心功能较差和血容量不足的老年病人全麻诱导，依托咪酯是首选的静脉麻醉诱导药。     

Effects of intravenous anesthetics on the human radial artery used as a coronary artery bypass graft

OBJECTIVE: Intravenous anesthetics are often used for anesthesia, sedation, and analgesia in the intraoperative and postoperative periods of coronary artery bypass graft (CABG) surgery. This study was designed to investigate the direct effects of intravenous anesthetics on the human radial artery (RA). DESIGN: In vitro, prospective with repeated measures. SETTING: University research laboratory. PARTICIPANTS: RA segments (n = 20) were obtained from CABG surgery patients and were divided into 3- to 4-mm vascular rings. INTERVENTIONS: Using the organ bath technique, the endothelium-independent vasodilatation function was tested in vitro by the addition of cumulative concentrations of thiopental, ketamine, etomidate, and propofol after vasocontraction by phenylephrine in the presence of N(G)-nitro-L-arginine methyl ester (L-NAME) and indomethacin. MEASUREMENTS AND MAIN RESULTS: Thiopental (10(-8) to 10(-4) mol/L), ketamine(10(-8) to 10(-4) mol/L), propofol (10(-8) to 3 x 10(-4) mol/L), and etomidate (10(-8) to 3 x 10(-4) mol/L) caused concentration-dependent vasorelaxation in human RA rings precontracted with phenylephrine in the presence of L-NAME and indomethacin (n = 20, for each drug). The pEC(50) and maximum relaxant effect values of thiopental and ketamine were significantly higher than for etomidate and propofol (p < 0.05). CONCLUSIONS: These findings indicate that thiopental, ketamine, etomidate, and propofol produce concentration-dependent relaxation on RA rings from humans. Thiopental and ketamine are more potent relaxant agents than etomidate and propofol. Intravenous anesthetics may be effective as alternative vasodilators for treatment of intraoperative and postoperative spasm of coronary artery grafts.     

Comparison of the effects of remifentanil or fentanyl on anaesthetic induction characteristics of propofol,thiopental or etomidate

BACKGROUND AND OBJECTIVE: This prospective, randomized, double-blinded study was designed to compare the effects of remifentanil or fentanyl on anaesthetic induction characteristics of propofol, thiopental or etomidate. METHODS: Seventy-two patients were enrolled in six groups of 12 individuals each. In three groups, fentanyl was given as a bolus dose of 1.5 microg kg(-1), whereas the others received a remifentanil infusion at 0.5 microg kg(-1) min(-1). Five minutes later, propofol, thiopental or etomidate were titrated to a state of unresponsiveness. Assessment included the amounts of drug necessary for induction, haemodynamics and the times to apnoea, loss of eyelash reflex, and the release of a water-filled syringe held in the patient's hand. RESULTS: Induction times to loss of the eyelash reflex were significantly shorter in the remifentanil than in the fentanyl groups: with propofol 50.7 +/- 13.6s (mean +/- SD) versus 74.9 +/- 27.0s (P < 0.01), with thiopental 42.9 +/- 16.8s versus 77.2 +/- 27.8s (P < 0.01) and with etomidate 54.7 +/- 17.6s versus 72.3 +/- 24.0s (P < 0.05). The times to respiratory arrest or for the syringe to fall were significantly shorter with remifentanil than with fentanyl for propofol and for thiopental, but not for etomidate. In terms of dosages per kg body weight necessary to achieve unresponsiveness, less propofol (-29%, P < 0.05), thiopental (-25%, P < 0.05) or etomidate (-32%, P < 0.01) was necessary with remifentanil than with fentanyl. Haemodynamic responses to tracheal intubation were controlled more effectively with remifentanil. However, within the remifentanil groups, mean arterial pressure significantly decreased during induction: -26% with propofol, -181% with thiopental and -14% with etomidate (all P < 0.01). CONCLUSIONS: During anaesthetic induction, a remifentanil infusion of 0.5 microg kg(-1) min(-1) over 5 min is a suitable alternative to a 1.5 microg kg(-1) bolus dose of fentanyl: induction times are shorter with reduced amounts of propofol, thiopental or etomidate.     

Comparative hemodynamic study of anesthesia induction with propofol (Diprivan), thiopental, methohexital, etomidate and midazolam in patients with coronary disease

In patients undergoing cardiac surgery, the induction of anesthesia is not without risk because of specific cardiovascular effects of the anesthetic and the preoperative state of the patient. The hemodynamic effects of etomidate, midazolam, thiopental, and methohexital are well known: etomidate is an anesthetic that induces only minor cardiovascular changes; its influence on the endocrine system, however, has reduced its clinical indication. Barbiturates such as thiopental and methohexital produce negative inotropic effects in combination with an increase in heart rate and myocardial oxygen consumption; midazolam reduces pre- and afterload in patients with poor left ventricular function. Propofol, a new short-acting induction agent with good anesthetic properties, is said to diminish arterial pressure as well as myocardial oxygen consumption. METHODS: In a randomized study we investigated the hemodynamic effects of intravenous induction with propofol (2 mg/kg body wt.), thiopental (5 mg/kg), methohexital (1 mg/kg), etomidate (0.3 mg/kg), and midazolam (0.15 mg/kg) in 50 patients undergoing coronary artery bypass grafting. All patients were premedicated with flunitrazepam (0.03 mg/kg up to 2 mg) and morphine hydrochloride (0.2 mg/kg up to 15 mg) 100 min before the investigation. After 0.003 mg/kg fentanyl the patients received the induction agent in the above-mentioned dosage within 40 s followed by 0.1 mg/kg pancuronium bromide. Hemodynamic measurements were performed 1, 3, and 5 min after the end of the injection as well as 1 and 5 min after intubation.(ABSTRACT TRUNCATED AT 250 WORDS)     

Substances used for local and general anaesthesia in major surgery suppress proliferative responsiveness of normal rat peripheral blood mononuclear cells in culture

We studied the direct effect of intravenous anaesthetics, local anaesthetics and premedication drugs in common use for major surgery, on the spontaneous versus lectin induced proliferation of cultured normal rat peripheral blood mononuclear cells, not exposed to surgical or any other trauma prior to culture. Peripheral blood mononuclear cells were incubated in cell-culture medium in the presence or in the absence of propofol, ketamine, fentanyl, midazolam, thiopental sodium, lidocaine or etomidate. The cells proliferated either spontaneously or under stimulation with a lectin phytohaemagglutinine P for 72 h. The proliferation rate was evaluated by 2H-Thymidine incorporation. Fentanyl, thiopental sodium, lidocaine and etomidate significantly inhibited phytohaemagglutinine P induced 3H-Thymidine incorporation in cultured rat peripheral blood mononuclear cells. Counts per minute of the cultures treated with these drugs were 1667.80 +/- 745.72, 1614.1 +/- 615.00, 1688.0 +/- 615.0 and 1549 +/- 560.41, respectively, compared with the phytohaemagglutinine P stimulated positive control counts per minute, 13488 +/- 4305.6 (P < 0.001 in each comparison). Propofol, ketamine and midazolam inhibited the lectin-induced cell proliferation to levels not statistically different from the baseline. Counts per minute of these cultures were 1361.90 +/- 745.73; 1108.90 +/- 751.33 and 1518.10 +/- 848.88, respectively. Compared either with the baseline 972.57 +/- 356.73 counts per minute or to the positive control culture counts per minute, 13488 +/- 4305.6 the difference was statistically significant (P < 0.001) in each comparison. All the substances tested in this study proved capable of exerting direct inhibitory effect on circulating immunocompetent cells, because the latter were not subjected to any other immunosuppressive factor, be it operative trauma, blood transfusion, malnutrition, drug abuse, prior to culture. The possible theoretical and practical implications are discussed in this study.     

The Comparative Amnestic Effects of Midazolam, Propofol, Thiopental, and Fentanyl at Equisedative Concentrations

Background: The authors evaluated the effects of midazolam, propofol, thiopental, and fentanyl on volunteer participants' memory for words and pictures at equisedative concentrations.

Methods: Sixty-seven healthy volunteers were randomized to receive intravenous infusions of midazolam (n = 11), propofol (n = 11), thiopental (n = 10), fentanyl with ondansetron pretreatment (n = 11), ondansetron alone (n = 8), or placebo (n = 16) in a double-blind design. Three increasing and then two decreasing sedative concentrations were achieved by computer-controlled infusion in each volunteer. Measures of sedation, memory, and drug concentration were obtained at each target concentration. Drug concentrations were normalized to equisedative effects using both Emax and logistic regression methods of pharmacodynamic modeling. The serum concentrations at 50% memory effect (Cp50s) were determined using four different memory end points. The relative potencies compared with midazolam for memory impairment were determined.

Results: Equisedative concentrations were midazolam, 64.5 +/- 9.4 ng/ml; propofol, 0.7 +/- 0.2 micro gram/ml; thiopental, 2.9 +/- 1.0 micro gram/ml; and fentanyl, 0.9 +/- 0.2 ng/ml. The Cp50s for 50% loss of memory for words were midazolam, 56 +/- 4 ng/ml; propofol, 0.62 +/- 0.04 micro gram/ml; thiopental, 4.5 +/- 0.3 micro gram/ml; and fentanyl, 3.2 +/- 0.4 ng/ml. Compared with midazolam, relative potencies (with 95% confidence intervals) were propofol, 0.96 (0.44-1.78); thiopental, 0.76 (0.52-0.94); and fentanyl, 0.34 (0.05-0.76). Large effects on memory were only produced by propofol and midazolam.     

静脉麻醉药抑制利多卡因致大鼠惊厥作用的比较

目的比较静脉麻醉药丙泊酚、依托咪酯、咪达唑仑及硫喷妥钠拮抗利多卡因致大鼠惊厥的作用。方法雄性Wistar大鼠36只,体重(250±20)g,随机均分为六组:空白对照组(C组)、利多卡因组(L组:利多卡因4mg·kg-1·min-1)、利多卡因+丙泊酚组(P组:利多卡因+丙泊酚12.5mg/kg)、利多卡因+依托咪酯组(E组:利多卡因+依托咪酯1.85mg/kg)、利多卡因+咪达唑仑组(M组:利多卡因+咪达唑仑0.65mg/kg)和利多卡因+硫喷妥钠组(T组:利多卡因+硫喷妥钠30.85mg/kg),惊厥后2h处死大鼠,取出脑组织分离双侧海马,一侧用于检测c-fos阳性细胞蛋白的表达。另一侧用于测定一氧化氮(NO)含量及一氧化氮合酶(NOS)活性。结果除C组外,其它五组大鼠均出现了惊厥,给予静脉麻醉药抑制惊厥,五组惊厥持续时间差异无统计学意义。L、P、E、M和T组c-fos阳性细胞表达、NO含量和NOS活性显著高于C组(P<0.05);P、E、M和T组c-fos阳性细胞表达、NO含量及NOS活性均显著降低于L组(P<0.05);M、T组c-fos阳性细胞表达、NO含量及NOS活性显著低于P、E组(P<0.05)。结论静脉麻醉药咪达唑仑、丙泊酚、依托咪酯及硫喷妥钠均可有效抑制利多卡因致惊厥作用,其中咪达唑仑与硫喷妥钠效果更显著。     

Direct comparative effects of halothane, enflurane, and isoflurane on oxygen supply and demand in isolated hearts

The authors examined the direct myocardial and coronary vascular responses to isoflurane, enflurane, and halothane and compared their effects on attenuating autoregulation of coronary flow (CF) as assessed by changes in the O2 supply-demand relationship. The effects of these anesthetics on left ventricular pressure (LVP), CF, percentage of O2 extraction, O2 delivery (DO2), and myocardial O2 consumption (MVO2) were examined in 47 isolated guinea pig hearts perfused at constant pressure. An increase in DO2 from control relative to MVO2 was used to indicate attenuation of autoregulation, and a decrease in MVO2 relative to DO2 to indicate a reduction of myocardial work and O2 utilization. Each heart was exposed to 0.51, 0.70, and 1.20 vol% halothane (n = 16); 0.91, 1.41, and 2.04 vol% enflurane (n = 16); or 0.45, 0.87, and 1.22 vol% isoflurane (n = 15). Adenosine (2 mM) was given to test maximal CF in arrested and in paced hearts. Mean results for increasing concentrations of each agent were as follows: LVP (average control 92 +/- 5 mmHg) (standard error of mean [SEM]) decreased by 15%,* 25%,* and 34%* with halothane; 13%,* 24%,* and 34%* with enflurane; and only 3%, 7%, and 13%* with isoflurane (*P less than 0.05 vs. controls). CF (control 6.1 +/- 0.3 ml.min-1.g-1) was not altered significantly with halothane or enflurane but increased by 6%, 9%, and 16%* with isoflurane and maximally by 86 +/- 7%* with adenosine. The percentage of O2 extraction (control 69.2 +/- 1.8%) decreased by 9%,* 16%,* and 22%* with halothane; 7%,* 15%,* and 22%* with enflurane; and only 1%, 4%, and 7%* with isoflurane.(ABSTRACT TRUNCATED AT 250 WORDS)     

Comparison of intracarotid anesthetics for EEG silence

The goal of this study was to compare systemic and cerebrovascular effects of three anesthetic drugs (etomidate, thiopental, and propofol) when delivered by intracarotid and intravenous routes in doses that produce electrocerebral silence (electroencephalography [EEG]). EEG activity, mean arterial pressure (MAP), and laser Doppler flow as a proxy of cerebral blood flow (CBF) of 24 anesthetized New Zealand white rabbits were continuously recorded. Data were compared at three timepoints: baseline, during EEG silence, and after recovery of EEG activity. Drugs were randomly injected via the carotid artery to produce 10 minutes of EEG silence. After 30 minutes of rest, intravenous boluses of the same drug were injected to achieve 10 minutes of EEG silence. During EEG silence, transient hypotension was seen with intracarotid propofol, but there was no decrease in CBF. MAP and CBF did not decrease with either intracarotid etomidate or thiopental during EEG silence. Intracarotid/intravenous dose ratio of propofol (26%+/-22%; n=8, P<0.02) was much higher than that of etomidate and thiopental (14%+/-2% and 19%+/-11%, respectively; NS). Collectively, these results suggest intracarotid etomidate and thiopental are more useful than propofol in producing EEG silence because they offer better dose advantage and are less likely to impair cerebral or systemic hemodynamics.     

Dose-related changes in the rate of cerebrospinal fluid formation and resistance to reabsorption of cerebrospinal fluid following administration of thiopental, midazolam, and etomidate in dogs

The rate of cerebrospinal fluid (CSF) formation (Vf) and resistance to reabsorption of CSF (Ra) were determined in dogs at four doses of thiopental (6, 12, 18, and 24 mg.kg-1.h-1), midazolam (0.5, 1.0, 1.5, and 2.0 mg.kg-1.h-1), and etomidate (0.86, 1.72, 2.58, and 3.44 mg.kg-1.h-1). Results were compared within and between groups and to previously reported normal values for Vf (0.030-0.054 ml/min) and Ra (220-240 cmH2O.ml-1.min) in dogs. At the two lower doses of thiopental, midazolam, or etomidate Vf was not significantly different than previously reported normal values. At the two higher doses of each drug Vf was 0.019-0.024 ml/min, significantly reduced compared to Vf at the two lower doses of each drug. The pattern of Ra data was more varied. With thiopental Ra was elevated at the lowest dose, (354 +/- 17 cmH2O.ml-1.min, mean +/- SD) reduced at the highest dose (156 +/- 19 cmH2O.ml-1.min), and not significantly different than previously reported normal values at the two intermediate doses. With midazolam Ra was elevated at the lowest and highest doses (332 +/- 25 and 378 +/- 18 cmH2O.ml-1.min) and normal at the two intermediate doses. With etomidate Ra was normal at the three lower doses and reduced at the highest dose (187 +/- 13 cmH2O.ml-1.min). It is concluded that CSF volume may be increased and the CSF pressure at which CSF volume contracts may be increased by doses of thiopental or midazolam that increase Ra, but not increased by etomidate.