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Biomedical subjects

M D Sokoll

Publications and source records attributed to M D Sokoll.

At least 19 recordsLinked to original sources
PubMed1991

Effect of (+/-)-DOI on neuromuscular transmission: a microelectrode study.

DOI (1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane) significantly depressed end plate current (EPC) amplitude. It decreased quantum content, increased the extent of neurally evoked EPC rundown during the train, produced a nonlinear current-voltage relationship, shortened time constant of decay, and depressed iontophoretically evoked EPC. The depressant response of DOI on EPC amplitude was antagonized by 5-HT1-like receptor antagonists, but was resistant to 5-HT2 and 5-HT3 receptor antagonists. This suggests that inhibitory 5-HT receptors roughly correspond to 5-HT1-like receptors.

Amphetamines↗
PubMed1991

Apology.

Explore the source record for details and available documents.

Publishing↗
PubMed1990

Neuromuscular and cardiovascular effects of mivacurium chloride (BW B1090U) during nitrous oxide-fentanyl-thiopentone and nitrous oxide-halothane anaesthesia.

Seventy-two adult surgical patients were studied to compare neuromuscular and cardiovascular effects of mivacurium chloride during nitrous oxide-fentanyl-thiopentone (BAL group) or nitrous oxide-halothane (HAL group) anaesthesia. Eighteen patients in the BAL group received an initial bolus of mivacurium, either the ED25 (n = 9) or the ED50 (n = 9) (0.03 and 0.05 mg kg-1). These doses were based on the assumption that the slope of the dose-response curve during nitrous oxide-opioid anaesthesia would be approximately the same as the slope of the neuromuscular response from the first human studies with mivacurium. Twenty-seven additional patients were allocated to subgroups of nine patients to receive mivacurium 0.04, 0.08 or 0.15 mg kg-1. Twenty-seven patients in the HAL group were allocated also to subgroups of nine patients to receive mivacurium 0.03, 0.04 or 0.15 mg kg-1. During stable anaesthesia, mean endtidal halothane concentrations were maintained at 0.49 +/- 0.01%. The estimated ED50, ED75 and ED95 for BAL and HAL groups were 0.039, 0.05 and 0.073 mg kg-1 and 0.040, 0.053 and 0.081 mg kg-1, respectively. Halothane did not potentiate maximum block or time to maximum block. Halothane did affect spontaneous recovery. With the 0.15-mg kg-1 dose, time to 95% recovery was prolonged significantly in the HAL group (30.0 (SEM 1.4) min) compared with the BAL group (24.1 (1.5) min). Recovery index from 25% to 75% recovery was also prolonged significantly in the HAL group (7.0 (0.4) min) compared with the BAL group (5.4 (0.4) min). There were no significant haemodynamic changes in groups given mivacurium doses up to and including 2 x ED95 by bolus i.v. administration.

Adolescent↗
PubMed1990

Anesthesia for craniotomy: a double-blind comparison of alfentanil, fentanyl, and sufentanil.

Using a prospective, randomized, and double-blind study design, alfentanil (n = 15), fentanyl (n = 14), or sufentanil (n = 16), in combination with N2O, were administered to patients undergoing craniotomy for supratentorial tumor resection. Physicians were given two syringes, one of which was labeled as "load" for the initial loading dose and the other as "maintenance" for continuous infusion. The concentration of drug in each syringe was adjusted to permit administration on a milliliter per kilogram basis. The target loading doses for alfentanil, fentanyl, and sufentanil were 75, 10, and 1 microgram/kg, respectively, and initial infusion rates were 33.5, 2.0, and 0.3 microgram.kg-1.h-1, respectively. Additional supplementary boluses and changes in maintenance infusion rate were made according to predetermined guidelines. Isoflurane, in increasing 0.2% inspired increments, was used only when the maximum allowed opioid dose had been given (i.e., supplementary bolus doses equal to 75% of the calculated loading dose or supplementary bolus doses equal to 50% of the calculated loading dose combined with a 50% increase in the maintenance infusion rate). Opioid infusions were stopped at the time of bone flap replacement. Antihypertensive medications and naloxone were subsequently given at the discretion of the anesthesiologist. Group demographics were not different. Total volumes of drug were similar among groups indicating equipotent preparations. Administration of isoflurane, antihypertensive medications, and naloxone were not different among groups. Although decreases in blood pressure seen with induction were similar among groups, alfentanil-treated patients received ephedrine more frequently before intubation. Thirty minutes after entry into the postanesthesia recovery area, respiratory rate and pH were lowest in sufentanil-treated patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Neuromuscular and cardiovascular effects of mivacurium chloride (BW B109OU) during nitrous oxide-narcotic, nitrous oxide-halothane and nitrous oxide-isoflurane anesthesia in surgical patients.

One hundred seventeen adult surgical patients were studied to compare neuromuscular and cardiovascular effects of mivacurium chloride during nitrous oxide-narcotic (BAL, n = 45) nitrous oxide-halothane (HAL, n = 27) and nitrous oxide-isoflurane (ISF, n = 45) anesthesia. Anesthesia was maintained with nitrous oxide (60%-70%) and oxygen (30%-40%) with end-tidal concentrations of halothane or isoflurane to yield a total MAC of approximately 1.25, or with supplemental fentanyl and thiopental as clinically indicated. Twitch response of the adductor pollicis muscle was elicited by supramaximal square wave pulses of 0.2 msec duration at a frequency of 0.15 Hz (Grass S44 stimulator) to the ulnar nerve and quantitated by a Grass FT10 transducer. Nine patients in each of the HAL and ISF groups received one of four doses of mivacurium (0.03, 0.05, 0.10 or 0.15 mg/kg). Ninety patients in the balanced anesthesia group received one of seven doses of mivacurium (0.03, 0.04, 0.05, 0.08, 0.15, 0.20, 0.25 mg/kg). The ED50, ED75 and ED95 of mivacurium in each group were estimated from linear regression plots of log dose versus probit of maximum percentage depression of twitch height. The ED50, ED75 and ED95 for halothane and isoflurane are 0.040, 0.053 and 0.081 and 0.037, 0.043 and 0.053, respectively. The ED50, ED75, and ED95 for the balanced group are 0.039, 0.050, and 0.073 mg/kg respectively. There was no significant difference between the slopes of the HAL and BAL inhalation anesthetic dose-response curves. The slope of the ISF group was significantly than the slope of the BAL group. Intercepts of the HAL and BAL curves were not different. The isoflurane curve's intercept was significantly less than the other groups' intercepts, lying above the halothane curve, but below the BAL curve. For the 0.05 mg/kg dose, maximum block was greater in the ISF group (89.1 +/- 2.7%, n = 9) than in the HAL (70.3 +/- 7.6%, n = 9) or BAL (67.7 +/- 6.4%, n = 9) groups. At higher doses of mivacurium, isoflurane produces a greater potentiation of neuromuscular block than halothane or balanced anesthesia. There were no significant cardiovascular changes seen in any group following mivacurium doses up to 0.15 mg/kg (approximately 2xED95).

Adult↗
PubMed1989

Halothane and isoflurane alter acetylcholine activated ion channel kinetics.

The effects of halothane and isoflurane on the acetylcholine activated ion channel were studied in the frog sartorius muscle using the two electrode voltage clamp technique. The miniature end-plate currents (MEPCs) were recorded and evaluated for amplitude, duration of growth phase and time constant of decay (tau). Both halothane and isoflurane decreased tau in a dose dependent manner. Depression of current amplitude was also dose dependent. The ED50 value indicates tau is more affected than the amplitude of MEPC. Biexponential decay phases were seen in a small fraction of cells exposed to a low concentration of halothane but not isoflurane. Biexponential decay, when seen, was more prominent at less negative clamped membrane potential. The normal linear relationship between membrane potential and tau was not altered by anesthetics.

Acetylcholine↗
PubMed1989

Neuromuscular and cardiovascular effects of mivacurium chloride in surgical patients receiving nitrous oxide-narcotic or nitrous oxide-isoflurane anaesthesia.

The neuromuscular and cardiovascular effects of mivacurium chloride were studied during nitrous oxide-oxygen narcotic (fentanyl) (n = 90) and nitrous oxide-oxygen isoflurane (ISO) anaesthesia (n = 45). In addition, a separate group (n = 9) received succinylcholine during fentanyl anaesthesia to compare its neuromuscular effects with mivacurium. Mivacurium was initially administered as a single bolus in doses from 0.03 mg.kg-1 to 0.25 mg.kg-1 to study the dose-response relationships, as well as the cardiovascular effects of mivacurium. Neuromuscular block (NMB) was measured by recording the twitch response of the adductor pollicis muscle following ulnar nerve stimulation (0.15 Hz, 0.2 ms supramaximal voltage). The ED95 values for mivacurium were estimated to be 0.073 mg.kg-1 and 0.053 mg.kg-1 in the fentanyl and ISO groups respectively. The duration of block (time from injection to 95 per cent recovery) for a dose of 0.05 mg.kg-1 mivacurium was 15.3 +/- 1.0 min and 21.5 +/- 1.3 min for fentanyl and ISO anaesthesia, respectively. The recovery index (25-75 per cent) between initial bolus dose (6.1 +/- 0.5 min), repeat bolus doses (7.6 +/- 0.6 min), mivacurium infusion (6.7 +/- 0.7 min) and succinylcholine infusion (6.8 +/- 1.8 min) were not significantly different. There was minimal change in mean arterial pressure (MAP) or heart rate (HR) following bolus doses of mivacurium up to 0.15 mg.kg-1. Bolus administration of 0.20 mg.kg-1 or 0.25 mg.kg-1 of mivacurium decreased MAP from 78.2 +/- 2.5 to 64.0 +/- 3.2 mmHg (range 12-59 per cent of control) (P less than 0.05). The same doses when administered slowly over 30 sec produced minimal change in MAP or HR.

Adult↗
PubMed1989

Nicardipine HCl: clinical experience in patients undergoing anaesthesia for intracranial aneurysm clipping.

Previous studies have reported haemodynamic interactions between dihydropyridine calcium antagonists and general anaesthesia. During anaesthesia for intracranial aneurysm surgery, we prospectively compared haemodynamic values obtained from 13 patients being treated with nicardipine HCl (0.15 mg.kg-1.hr-1 IV) for cerebral vasospasm against values obtained from 11 untreated controls. Prior to induction of anaesthesia, nicardipine-treated patients had significantly elevated mean +/- SD cardiac index (5.67 +/- 1.30 vs 3.99 +/- 0.73 L.min-1.m-2) while MAP (86 +/- 10 vs 99 +/- 14 mmHg) and systemic vascular resistance (647 +/- 227 vs 1141 +/- 404 dynes.sec-1.cm-5) were reduced. Heart rate, CVP, and PACWP were similar between groups. Anaesthesia induction and tracheal intubation resulted in similar haemodynamic values between groups with the exception of CVP (10 +/- 5 vs 5 +/- 2 mmHg) and PACWP (15 +/- 5 vs 8 +/- 3 mmHg) which were elevated in the nicardipine group (P less than 0.01). Mannitol infusion and deliberate hypotension resulted in nearly identical haemodynamic responses in both groups. Nicardipine-treated patients required more intravenous fluids during the operative procedure (2.4 +/- 0.3 L vs 1.5 +/- 0.4 L, P less than 0.05) and were less likely to require isoflurane supplementation to morphine sulphate/nitrous oxide anaesthesia (P less than 0.01). In summary, our experience with nicardipine HCl revealed no major untoward effects with respect to maintenance of intraoperative haemodynamic stability despite continuous antivasospasm therapy with this vasodilator.

Adult↗
PubMed1989

Nicardipine after spinal cord compression in the lamb.

To study the effects of the calcium channel blocker nicardipine on spinal cord blood flow and spinal evoked potentials, the following study was undertaken. After cord compression, which was productive of paraparesis, nicardipine was administered intravenously in 10 anesthetized lambs. Ten control animals were subjected to compression but received saline instead. Nicardipine produced a significant decrease in mean arterial pressure when compared to the control group. Thirty minutes after compression, spinal cord blood flow also was lower in the nicardipine group compared with controls. Spinal evoked potentials did not recover after compression in either group.

Animals↗
PubMed1988

Neuromuscular blocking action of two hemicholinium-3 analogs.

Two hemicholinium-3 (HC-3) analogs (NAM-204 and NAM-224) in which the C = O moiety was reduced to -CH2 and 2- or 3-CH3 substitution on the piperidine ring were demonstrated to produce a different type of neuromuscular inhibition than that induced by HC-3. The neuromuscular blocking activity was tested in several different preparations and it was shown that these compounds are potent, short-acting, and was reversed by neostigmine but not by choline. Although these compounds possess weak anticholinesterase activity, significant alterations of blood pressure and heart rate are absent. Miniature end-plate potentials' amplitude were found to be diminished by these compounds with some alteration of frequency. In voltage-clamped frog sartorius muscle NAM-224 and NAM-204 decreased amplitude of miniature end-plate current (mepcs) and accelerated the time constant of mepc decay in a concentration-dependent manner, without altering the single exponential nature of mepc decay. NAM-204 and NAM-224 at high concentrations also produced a voltage- and concentration-dependent non-linearity in current/voltage relationships, especially at more negative membrane potentials. Hence, these pharmacological and electrophysiological studies indicate NAM-224 and NAM-204 have significant activity at both pre- and post-junctional sites and their post-junctional blocking activity results from blocking ACh receptor/ion channel complex.

Action Potentials↗
PubMed1988

The neuromuscular blocking and cardiovascular effects of doxacurium chloride in patients receiving nitrous oxide narcotic anesthesia.

The purpose of this study was to evaluate neuromuscular and cardiovascular effects of doxacurium chloride, a new long-acting neuromuscular blocking agent, during a stable state of nitrous oxide and narcotic anesthesia. Ninety-three ASA physical status I or II patients were studied after informed written consent had been obtained. Eighty-one patients (group A) received doxacurium. The 81 patients were divided into nine subgroups according to the dose of doxacurium administered (0.01-0.06 mg.kg-1). Patients in a control group (group B) (n = 12) received pancuronium. To assess neuromuscular responses, a force displacement transducer recorded the twitch response of the adductor pollicis muscle following ulnar nerve stimulation. The ED50 and ED95 for doxacurium were estimated to be 0.013 mg.kg-1 and 0.023 mg.kg-1, respectively. The time to maximum twitch suppression following a dose of 1.0 (ED95) and 1.7 (ED95) was 10.3 +/- 1.3 min and 7.6 +/- 0.8 min, respectively. After an ED95 dose of doxacurium the time to spontaneous recovery to 95% of control twitch height was 73.7 +/- 8.7 min. With larger doses of doxacurium, 0.04 mg.kg-1 (1.7 X ED95) and 0.05 mg.kg-1 (2.2 X ED95), the time to spontaneous recovery to 95% of control twitch height was 125.8 +/- 24.8 and 204.0 +/- 21.2 minutes, respectively. When 25% twitch height recovery or more was present the reversal of doxacurium induced neuromuscular blockade was prompt.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1988

Accelerated onset of non-depolarizing neuromuscular blocking drugs: pancuronium, atracurium and vecuronium. A comparison with succinylcholine.

The time of onset and degree of neuromuscular blockade (NMB) in 80 anaesthetized patients, following either a single bolus injection of pancuronium 0.95 mg kg-1, atracurium 0.53 mg kg-1 or vecuronium 0.07 mg kg-1, or divided doses of pancuronium 0.15 mg kg-1, atracurium 0.07 mg kg-1 or vecuronium 0.01 mg kg-1 administered 3 min or 5 min before the second dose of pancuronium 0.08 mg kg-1, atracurium 0.46 mg kg-1 or vecuronium 0.06 mg kg-1, were determined and compared to the same parameters measured following succinylcholine administration (1 mg kg-1). The time to maximum NMB (100%) following the administration of succinylcholine was 58.1 +/- 5.3 s, whereas the time to maximum NMB (100%) following a single bolus injection of either pancuronium, atracurium or vecuronium was 130.6 +/- 22.2, 93.0 +/- 6.4, 127.5 +/- 13.0 s, respectively. These values for time to maximum NMB are significantly longer than the time required for succinylcholine to achieve maximal blockade. The time to attain maximum NMB following divided doses of pancuronium, atracurium or vecuronium separated by 3 min decreased significantly to 77.9 +/- 4.3, 77.5 +/- 7.6, 89.0 +/- 8.6 s, respectively. However, when the two doses of drug were separated by 5 min, only small, non-significant further decreases occurred in the time required to achieve maximum blockade. Although the time to maximum NMB following divided doses of pancuronium, atracurium or vecuronium is significantly longer than that for succinylcholine, divided dosing significantly decreases the time required to reach maximal NMB.

Adolescent↗
PubMed1987

Pharmacologic evaluation and structure activity relationships of a series of hemicholinium-3 (HC-3) analogs.

Piperidine derivatives of hemicholinium-3 were synthesized, which included the following spacing groups between cationic heads: trans-trans-bicyclohexyl, phenanthrene, naphthalene, and biphenyl. Relatively minor structural alterations in these series of compounds resulted in several different types of pharmacological actions related to cholinergic transmission. Structural requirements of the compounds are discussed and include internitrogen distance, structural planarity, spacing groups, and positional isomerism of the quaternary cationic heads. Selected quaternary piperidine derivatives with 14 A inter-atomic distance between the cationic heads exhibit potent HC-3 like activity which is enhanced if a molecule has a nonpolar space filling group (4-methyl piperidine) approximately 3.7 A from the corresponding quaternary cationic head. With selected piperidine ring substitutions, active tertiary amines were also identified. Compounds containing C = O in the spacing moiety were active inhibitors of cholinesterase with some derivatives being nearly as active as physostigmine. When the C = O moiety was reduced to -CH2 and a 2 or 3-CH3 piperidine ring was present, potent non-depolarizing, short acting neuromuscular blocking agents were obtained.

Animals↗
PubMed1986

Circulatory effects of atracurium in patients with cardiovascular disease.

Atracurium 0.4 mg kg-1, which was sufficient to produce neuromuscular blockade sufficient for intubation, was administered as divided bolus doses to 40 patients with severe cardiovascular disease. Little haemodynamic change occurred. A transient reduction in arterial pressure was noted in one patient. Atracurium was found to be safe and effective, and administration in small bolus doses separated by 30 s may reduce the likelihood of significant circulatory changes.

Anesthesia, General↗