Local anesthetics at a concentration of 10 mM(procaine and lidocaine) were found to inhibit competitively Ca++ binding to lipidextracted RBC membrane, and also to egg albumin film fixed on cover glasses or impregnated into Whatman filter paper (No. 1). A competitive inhibition by local anesthetics was also found in Ca++ binding to Whatman filter paper which had been pretreated with organic solvents to extract possible contaminated lipids. Therefore, it is suggested that the local anesthetics inhibit Ca++ binding not only to phospholipids but to some macromolecules such as membrane proteins, egg albumin film and filter paper.
Anesthetics, Local/pharmacology* ; Calcium/metabolism* ; Cell Membrane Permeability/drug effects ; Erythrocytes/cytology* ; Filtration ; Human ; Lidocaine/pharmacology ; Ovalbumin/metabolism* ; Procaine/pharmacology

The cerebral vasospasm which often accompanies a subarachnoid hemorrhage from a ruptured intracranial aneurysm is one the chief reasons for morbidity and motarlity. Although the phenomenon still needs clarification, experimental evidence has indicated that alpha-blocking agents can modify this blood-induced spasm. A disappointing experience with these agents led to a clinical trial of the beta-adrenergic drug isoproterenol. In 1975 Sundt reported a good final result with the use of isoproterenol and lidocaine hydrochloride in the treatment of cerebral ischemia attributed to progressive vasospasm after a subarachnoid hemorrhage in human beings. We have reported our experience with the use of isoproterenol and lidocaine hydrochloride in 5 such cases. 3 were treated preoperatively and 2 postoperatively. Experience suggests that the drug regimen reported is useful when institute early after the onset of symptoms and is safe with proper monitoring techniques. The symptomatology of cerebral vasospasm, the reationable for this form of therapy, and the pharmacology of the drugs were discussed.
Brain Ischemia ; Humans ; Intracranial Aneurysm* ; Isoproterenol* ; Lidocaine* ; Pharmacology ; Spasm ; Subarachnoid Hemorrhage ; Vasospasm, Intracranial*

OBJECTIVETo examine the effects of procaine and lidocaine on intracellular Ca(2+) release from sarcoplasmic reticulum ryanodine-sensitive Ca(2+) stores.

METHODSThe experiment was performed on hippocampal slices from 60-80 g male Mongolian gerbils. Levels of intracellular Ca(2+) concentration in the slices were measured by microfluorometry. The slices were perfused with 50 mmol/L KCl containing medium for 30 seconds. Then, the medium was switched to physiological medium. After 5 min of incubation, the slice was perfused with 20 mmol/L caffeine containing physiology medium for 2 min. Following incubation, the slice was superfused with physiological medium until the end of the experiment. The effects of procaine and lidocanin (100 micro mol/L) on caffeine-evoked Ca(2+) release were evaluated by adding them to the medium after high K(+) medium perfusion.

RESULTSCaffeine induced a marked increase in intracellular Ca(2+) concentration which was then decreased 12% upon the addition of procaine (P < 0.05); however, lidocaine, did not induce a similar inhibitory reaction.

CONCLUSIONProcaine inhibits ryanodine-receptor mediated Ca(2+) release from intracellular Ca(2+) stores, while lidocaine may inhibit Ca(2+) release through other mechanisms.

Anesthetics, Local ; pharmacology ; Animals ; Calcium ; metabolism ; Gerbillinae ; Hippocampus ; drug effects ; metabolism ; Lidocaine ; pharmacology ; Male ; Procaine ; pharmacology ; Ryanodine ; pharmacology ; Ryanodine Receptor Calcium Release Channel ; physiology

AIMTo study the cutaneous permeation kinetics and pharmacodynamics of lidocaine gel.

METHODSThe concentration of lidocaine in dermis following topical application in rats was determined by the cutaneous microdialysis technique and related parameters were calculated; the pharmacodynamics of the gel was evaluated by electric stimulation method with EMLA (eutectic mixture of local anesthetics) cream as a control.

RESULTSThe peak of percutaneous absorption kinetic profile of lidocaine gel across rat skin occurred at 1.25 h; the onset time of local anesthetic action of lidociane gel was similar to that of EMLA, but both the duration and depth of anesthetic effect were superior to EMLA cream.

CONCLUSIONLidocaine gel showed good anesthetic effect. The minimum effective concentration of lidocaine in dermis is 12 mg.L-1.

Anesthesia, Local ; Anesthetics, Local ; pharmacokinetics ; pharmacology ; Animals ; Gels ; Lidocaine ; pharmacokinetics ; pharmacology ; Male ; Pain Threshold ; drug effects ; Prilocaine ; pharmacokinetics ; pharmacology ; Random Allocation ; Rats ; Rats, Wistar ; Skin Absorption

This study is to investigate the effects of phenytoin sodium, lidocaine (sodium channel blockers), propranolol (beta-adrenergic receptor antagonist), amiodarone (drugs prolonging the action potential duration) and verapamil (calcium channel blockers) on arrhythmia of mice induced by Bufonis Venenum (Chansu) and isolated mouse hearts lethal dose of Chansu. Arrhythmia of mice were induced by Chansu and then electrocardiograms (ECGs) were recorded. The changes of P-R interval, QRS complex, Q-T interval, T wave amplitude, heart rate (HR) were observed. Moreover, arrhythmia rate, survival rate and arrhythmia score were counted. Isolated mouse hearts were prefused, and the lethal dose of Chansu was recorded. Compared with control group, after pretreatment with phenytoin sodium, broadening of QRS complex and HR were inhibited, and the incidence of ventricular arrhythmia was reduced dramatically, while survival rate was improved; the isolated mouse hearts lethal dose of Chansu was increased significantly. After pretreatment with lidocaine, the prolongation of P-R interval and broadening of QRS complex were inhibited, and the incidences of ventricular arrhythmia were reduced dramatically, while survival rate was improved; the isolated mouse hearts lethal dose of Chansu was increased significantly. After pretreatment with propranolol, prolongation of P-R interval, broadening of QRS complex, prolongation of Q-T interval and HR were inhibited, and the incidences of both supraventricular and ventricular arrhythmias were reduced dramatically, while survival rate was improved. After pretreatment with amiodarone, HR was inhibited, the incidences of ventricular tachycardia were reduced dramatically. Lastly, after pretreatment with verapamil, the prolongation of P-R interval and Q-T interval were inhibited and the incidences of both supraventricular and ventricular arrhythmias were reduced dramatically; the isolated mouse hearts lethal dose of Chansu was reduced significantly. In in vivo experiments, phenytoin sodium was most effective against the mice arrhythmias induced by Chansu while cautious use of verapamil for Chansu inducing arrhythmia should be noted. It is also concluded that mice ventricular arrhythmias induced by Chansu might be most closely related to sodium channel, supraventricular arrhythmias might be related to beta-adrenergic receptor, and calcium channel plays an important role in conduction block. In in vitro experiments, phenytoin sodium was most effective, followed by lidocaine and propranolol, and amiodarone had no obvious effect and verapamil reduced the lethal dose of Chansu.
Amiodarone ; pharmacology ; Animals ; Anti-Arrhythmia Agents ; pharmacology ; Arrhythmias, Cardiac ; chemically induced ; physiopathology ; Bufanolides ; toxicity ; Electrocardiography ; drug effects ; Female ; Heart Rate ; drug effects ; In Vitro Techniques ; Lethal Dose 50 ; Lidocaine ; pharmacology ; Male ; Mice ; Phenytoin ; pharmacology ; Propranolol ; pharmacology ; Verapamil ; pharmacology

AIMTo observe the effects of lidocaine and thiopental on the neuronal injury induced by the experimental ischemia in hippocampus slice cultures obtained from postnatal 22 days SD rats.

METHODSModel of the experimental ischemia was produced by hypoxia and glucose deprivation. Propidium iodide (PI) assay was used to observe the neuronal injury in CA1 and dentate gyrus (DG).

RESULTSAfter experimental ischemia, the peak of PI index was appeared in CA1 and DG on the first day (P < 0.01), PI index in DG was less than in CA1 (P < 0.01). PI indices were still higher during seven days after the experimental ischemia than before the experimental ischemia (P < 0.01). 10 nmol/L and 100 nmol/L concentration of lidocaine could significantly decrease PI indices in CA1 and DG (P < 0.01). 250 nmol/L and 600 nmol/L concentration of thiopental also decreased the PI indices in CA1 and DG (P < 0.01). The neuronal injury peaks were postponed to the third day after the experimental ischemia by lidocaine and thiopental.

CONCLUSIONIt suggested that lidocaine and thiopental could decrease the neuronal injury in CA1 and DG induced by the experimental ischemia, and postpone the neuronal injury peaks to the third day after the experimental ischemia.

Animals ; Brain Ischemia ; pathology ; CA1 Region, Hippocampal ; drug effects ; pathology ; In Vitro Techniques ; Lidocaine ; pharmacology ; Neurons ; drug effects ; pathology ; Rats ; Thiopental ; pharmacology

OBJECTIVE: To investigate the effect of lidocaine on LPS induced apoptosis of cultured adult rat alveolar Type II (AT-II) cells. METHODS: Cultured cells were exposed to LPS and lidocaine for 24 hours. Apoptosis and necrosis rates of cells were detected by flow cytometry and electron microscope. The activity of lactic dehydrogenase (LDH) was analyzed by using LDH kits. RESULTS: LPS induced the AT-II cell injuries by increasing not only the necrosis and apoptosis rates but also the LDH release of cultured AT-II in vitro. Lidocaine decreased the necrosis and apoptosis rates of AT-II cells. CONCLUSION Lidocaine can directly inhibit the apoptosis and necrosis induced by LPS in cultured AT-II cells.
Animals ; Apoptosis ; drug effects ; Cells, Cultured ; Epithelial Cells ; pathology ; Flow Cytometry ; Lactate Dehydrogenases ; metabolism ; Lidocaine ; pharmacology ; Lipopolysaccharides ; Necrosis ; Protective Agents ; pharmacology ; Pulmonary Alveoli ; pathology ; Rats ; Rats, Sprague-Dawley

BACKGROUND: Sevoflurane is widely used to anesthetize children because of its rapid action with minimal irritation of the airways. However, there is a high risk of agitation after emergence from anesthesia. Strabismus surgery, in particular, can trigger agitation because patients have their eyes covered in the postoperative period. The aim of this study was to determine whether or not esmolol and lidocaine could decrease emergence agitation in children. METHODS: Eighty-four patients aged 3 to 9 years undergoing strabismus surgery were randomly assigned to a control group (saline only), a group that received intravenous lidocaine 1.5 mg/kg, and a group that received intravenous esmolol 0.5 mg/kg and lidocaine 1.5 mg/kg. Agitation was measured using the objective pain score, Cole 5-point score, and Richmond Agitation Sedation Scale score at the end of surgery, on arrival in the recovery room, and 10 and 30 min after arrival. RESULTS: The group that received the combination of esmolol and lidocaine showed lower OPS and RASS scores than the other two groups when patients awoke from anesthesia (OPS = 0 (0-4), RASS = -4 [(-5)-1]) and were transferred to the recovery room (OPS = 0 (0-8), RASS = -1 [(-5)-3]) (P < 0.05). There was no significant difference in the severity of agitation among the three groups at other time points (P > 0.05). CONCLUSIONS: When pediatric strabismus surgery is accompanied by sevoflurane anesthesia, an intravenous injection of esmolol and lidocaine could alleviate agitation until arrival in the recovery room. TRIAL REGISTRATION Clinical Research Information Service, No. KCT0002925; https://cris.nih.go.kr/cris/en/search/search_result_st01.jsp?seq=11532.
Anesthesia ; methods ; Child ; Child, Preschool ; Double-Blind Method ; Humans ; Injections, Intravenous ; Lidocaine ; administration & dosage ; pharmacology ; Propanolamines ; administration & dosage ; pharmacology ; Sevoflurane ; therapeutic use ; Strabismus ; surgery ; Wakefulness ; drug effects

OBJECTIVETo compare the effects of epidural anesthesia with 1.5% lidocaine and 0.5% ropivacaine on propofol requirements, the time to loss of consciousness (LOC), effect-site propofol concentrations, and the hemodynamic variables during induction of general anesthesia guided by bispectral index (BIS) were studied.

METHODSForty-five patients were divided into three groups to receive epidurally administered saline (Group S), 1.5% (w/w) lidocaine (Group L), or 0.5% (w/w) ropivacaine (Group R). Propofol infusion was started to produce blood concentration of 4 mug/ml. Once the BIS value reached 40~50, endotracheal intubation was facilitated by 0.1 mg/kg vecuronium. Measurements included the time to LOC, effect-site propofol concentrations, total propofol dose, mean arterial blood pressure (MABP), and heart rate (HR) at different study time points.

RESULTSDuring induction of anesthesia, both Groups L and R were similar for the time to LOC, effect-site propofol concentrations, total propofol dose, MABP, HR, and BIS. The total doses of propofol administered until 1 min post-intubation were significantly less in patients of Groups R and L compared with Group S. MABP and HR were significantly lower following propofol induction compared with baseline values in the three groups, or MABP was significantly increased following intubation as compared with that prior to intubation in Group S but not in Groups R and L while HR was significantly increased following intubation in the three groups.

CONCLUSIONEpidural anesthesia with 1.5% lidocaine and 0.5% ropivacaine has similar effects on the time to LOC, effect-site propofol concentrations, total propofol dose, and the hemodynamic variables during induction of general anesthesia.

Adult ; Amides ; pharmacology ; Anesthesia, Epidural ; Anesthesia, General ; Anesthetics, Local ; pharmacology ; Blood Pressure ; drug effects ; Electroencephalography ; Female ; Heart Rate ; drug effects ; Humans ; Lidocaine ; pharmacology ; Male ; Middle Aged ; Propofol ; pharmacology ; Time Factors

BACKGROUND: Interruption of efferent sympathetic fibers is the mainstay of therapy in reflex sympathetic dystrophies(RSD) and be accomplished by temporary or permanent anesthetic blockade of sympathetic ganglia, surgical lesions of the sympathetic trunk, intravenous injecton of guanethidine or reserpine, or by systemic administration of adrenergic blocking drugs. In this study, the effects and the side effects of intravenous regional bretylium for the treatment of RSD were studied. METHODS: Seven patients have been administered with 2.0 mg/kg bretylium in 0.25% lidocaine with 100U of heparin three times weekly. A standard intravenous regional technique was used with 250~300 mmHg tourniquet pressure for 30 minutes. Blood pressure and pulse rate were monitored before injection, 1 minute and 5 minutes after injection, immediately before deflation of tourniquet, 1 minute, 5 minutes and 30 minutes after deflation of tourniquet. Pain and temperature evaluations were made before injection and at 1 week after every injection. RESULTS: The increase in skin temperature and decrease in pain score of the affected limb were noted after the use of bretylium in 5 patients out of 7 patients. These clinical effects probably resulted from bretylium,s ability to accumulate in adrenergic nerves and block norepinephrine release. One patient had hypotension immediately after tourniquet deflation. CONCLUSIONS: Intravenous regional bretylium provides significant pain relief for treatment of RSD.
Adrenergic Fibers ; Blood Pressure ; Extremities ; Ganglia, Sympathetic ; Guanethidine ; Heart Rate ; Heparin ; Humans ; Hypotension ; Lidocaine ; Norepinephrine ; Pharmacology ; Reflex Sympathetic Dystrophy* ; Reflex* ; Reserpine ; Skin Temperature ; Tourniquets