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Biomedical subjects

I Kissin

Publications and source records attributed to I Kissin.

At least 73 records · Page 4Linked to original sources
PubMed1987

Barbiturates inhibit stress-induced analgesia.

The effect of pentobarbitone and thiopentone on stress-induced analgesia was studied in 40 male Sprague-Dawley rats. Antinociception was determined by measuring motor reaction threshold to the noxious pressure on the tail with the use of an "Analgesymeter." Stress was induced by placement of a clamp on the hind paw. The stress procedure was found to cause an increase in reaction threshold, which was partially suppressed by naloxone 0.5 mg X kg-1. Pentobarbitone in a subanaesthetic dose of 25 mg X kg-1, SC, almost completely abolished the stress-induced increase in the reaction threshold (an increase in reaction threshold from 329 +/- 33 g to 486 +/- 62 g in control group, and from 250 +/- 26 g to 273 +/- 35 g in pentobarbitone group, p less than 0.02 for the difference in the threshold changes). Thiopentone used in a dose of 25 mg X kg-1, IV, caused a loss of the righting reflex for 37 +/- 10 minutes; stress procedure applied ten minutes after regaining the righting reflex did not cause any increase in the reaction threshold (with an increase in the reaction threshold in control group from 355 +/- 50 g to 540 +/- 26 g, p less than 0.001 for the difference between the groups). The results suggest that the barbiturates in subanaesthetic doses inhibit stress-induced analgesia. Thiopentone used in an anaesthetic dose has the potential for inhibition of stress-induced analgesia in the period of recovery from anaesthesia.

Animals↗
PubMed1987

Pentobarbital and thiopental anesthetic interactions with midazolam.

The effects of midazolam-pentobarbital and midazolam-thiopental combinations on the righting reflex were studied in rats. Doses that block the righting reflex for the agents given alone and for their combinations were determined with a probit procedure and compared with an isobolographic analysis. Interactions between pentobarbital or thiopental and midazolam were found to be synergistic (supra-additive). The degree of synergism was almost identical with both combinations. The ability of barbiturates to increase the affinity of benzodiazepine receptors to midazolam may be the underlying mechanism for the observed synergism.

Anesthesia, General↗
PubMed1987

Morphine and fentanyl hypnotic interactions with thiopental.

The effects of morphine-thiopental and fentanyl-thiopental combinations on the righting reflex were studied in rats. Doses that block the righting reflex for the agents given alone and for their combinations were determined with a probit procedure and compared with an isobolographic analysis. Interaction between morphine or fentanyl and thiopental on blockade of the righting reflex were both found to be synergistic. The degree of synergism was relatively small for the fentanyl-thiopental combination; the maximal deviation from additive interaction (expected/observed ratio) for ED50 dose level was 1.15 (P less than 0.01). The degree of synergism was greater for the morphine-thiopental combination; the maximal deviation from additive interaction was 2.27 (P less than 0.001). Comparison of the results with the outcomes of opioid-barbiturate interactions in relation to blockade of purposeful movement response to tail clamping, which was antagonistic, shows that the combination of a barbiturate with an opioid gives different outcomes for different end-points of anesthesia. This suggests that the anesthetic effect of an agent is composed of several components, each with a different mechanism of action.

Animals↗
PubMed1987

Midazolam antagonizes the analgesic effect of morphine in rats.

The effect of midazolam on morphine analgesia was studied in 54 rats. Analgesia was determined by measuring threshold for motor response to noxious pressure applied to the tail. Midazolam (0.5 mg/kg) decreased the morphine-induced (1 mg/kg) increase in the reaction threshold by one-half. Flumazepil (Ro 15-1788), a specific antagonist of benzodiazepines, prevented inhibition of morphine antinociception by midazolam. These findings demonstrate that midazolam partially antagonizes the analgesic effect of morphine and, in addition, that the antagonism of midazolam on morphine analgesia is mediated by benzodiazepine receptors.

Animals↗
PubMed1987

Sympathetic blockade increases tactile sensitivity.

To determine whether tactile sensitivity of the normal skin is altered by suppression of sympathetic efferent activity, the effect of stellate ganglion block and epidural sympathetic block on touch threshold was studied. The study was performed on ten individuals with various chronic pain syndromes. Tactile sensitivity was measured in the normal skin area with the use of von Frey filaments and a two-alternative forced-choice procedure with a staircase presentation of touch stimuli. With stellate ganglion block, touch threshold decreased on the side of the block by 48.8 +/- 8.% (P = 0.002) without any significant change in the threshold on the healthy, nonblocked side (P = 0.003 for the difference between the sides). With epidural sympathetic block, touch threshold decreased to the same extent on the diseased and healthy sides, which were both affected by the block (46.2 +/- 11.4%, P = 0.027 and 47.7 +/- 12.5%, P = 0.032, respectively). The results show that sympathetic blockade increases tactile sensitivity. They also suggest that sympathetic efferent activity modulates the function of tactile receptors. It is hypothesized that the sympathetic modulation makes tactile receptors less sensitive to touch, less specific, and probably more prone to code tactile stimuli in such a way that the brain recognizes this code as pain.

Adult↗
PubMed1986

Selective kappa opioid agonist for spinal analgesia without the risk of respiratory depression.

The effects of the selective kappa agonist, U-50,488H, on the motor response to noxious mechanical stimulation when administered intrathecally, as well as on respiratory rate and PaCO2 when administered by intracerebroventricular injection, were compared with those of morphine in experiments on rats. The agonist U-50,488H caused a dose-dependent increase in the threshold to noxious stimulation but did not have a potential for depression of resting ventilation. The results suggest that selective kappa opioid agonists may be suitable for clinical spinal (epidural) analgesia without the associated risk of respiratory depression.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed1986

Spinal and supraspinal mechanisms for morphine-pentobarbital antinociceptive interaction in relation to cardiac acceleration response in rats.

In rat experiments, morphine-pentobarbital antinociceptive interaction affecting cardiac acceleration in response to somatic noxious stimulation was analyzed with the use of intrathecal and intracerebroventricular injections of morphine. Cardiac acceleration response was induced by tail compression, and heart rate was monitored by electrocardiogram. Pentobarbital, in a subanesthetic intravenous dose, antagonized the antinociceptive effect of morphine in relation to cardiac acceleration response when morphine was administered intracerebroventricularly. Without pentobarbital, morphine, 8 micrograms, almost completely blocked the cardiac acceleration response, which was only 1 +/- 1 beats/min. When pentobarbital (10 mg/kg intravenously) was administered in a combination with the same dose of morphine, the cardiac acceleration response was 29 +/- 3 beats/min (P less than 0.0001). In contrast, when morphine was administered intrathecally, the antagonism by pentobarbital of the cardiac acceleration response was absent. The results suggest that supraspinal mechanisms play a decisive role in morphine-pentobarbital antagonism in relation to cardiac acceleration response to somatic noxious stimulation.

Animals↗
PubMed1986

Morphine and fentanyl interactions with thiopental in relation to movement response to noxious stimulation.

The effects of morphine-thiopental and fentanyl-thiopental combinations on the movement response caused by tail clamping were studied in rats. Doses that prevented movement response when the agents were given singly and when the agents were given in combination were determined by a probit procedure and compared with isobolographic analysis. With doses of the above agents sufficient to block the movement response to tail clamping (ED50 values: 4.7 (3.3-6.6) mg/kg intravenously for morphine; 8.3 (5.8-11.3) micrograms/kg intravenously for fentanyl; and 18.8 (17.9-19.7) mg/kg intravenously for thiopental) both fentanyl and, to a lesser extent, morphine have a less than additive or an antagonistic interaction with thiopental. This antagonism is a relative one that does not increase the requirement for one agent upon the addition of another agent.

Animals↗
PubMed1985

A microcomputer based controller for neuromuscular block during surgery.

A microcomputer based control system has been developed to automatically induce and maintain neuromuscular block during surgery. The system repeatedly adjusts the infusion rate of a muscle relaxant, succinylcholine, based on the evoked, rectified, and integrated electromyogram (EMG). The system was tested in 12 patients for a 30-min infusion period with a setpoint of 80% depression of the evoked, rectified, and integrated thenar EMG. The mean time to reach the setpoint for 10 of the patients was 5.5 (+/- 1.87 SD) min and the mean time for 95% recovery after infusion was stopped was 5.4 (+/- 0.83 SD) min. Average overshoot was 9.9% of the baseline (+/- 3.1% SD), and the average time within +/- 10% of the setpoint was 22.1 min (+/- 7.26 SD). The total dose of succinylcholine for these 10 patients ranged from 1.21 to 3.77 mg/kg with a mean of 1.92 mg/kg. The other two patients were relatively insensitive to the drug and the controller was unable to bring the response to the setpoint due to a ceiling placed on infusion rate by the control algorithm.

Computers↗
PubMed1985

Reserpine-induced changes in anesthetic action of fentanyl.

The effect of prior administration of reserpine on fentanyl dose-response curves for loss of the righting reflex and prevention of purposeful movement response to noxious stimulation was studied in rats. It was found that reserpine (5 mg X kg-1, 3 h before the tests) antagonized the effect of fentanyl on purposeful movement response to the tail clamp and, at the same time, strengthened its effect on the righting reflex. As a result, reserpine pretreatment reversed the order of fentanyl potency regarding these two effects. Reserpine changed fentanyl ED50 values for the purposeful movement response from 8.2 to 20.3 micrograms X kg-1 (P less than 0.0001) and for the righting reflex from 20.5 to 13.7 micrograms X kg-1 (P less than 0.0001). The results suggest that reserpine dissociates the analgesic action of fentanyl from its anesthetic action, defined as a loss of the righting reflex. This may be regarded as an indication that the analgesic action of narcotics may not adequately reflect their anesthetic potency.

Analgesics↗
PubMed1985

Cardiovascular effects of esmolol in anesthetized humans.

We studied the cardiovascular effects of esmolol, a newly synthesized beta-adrenocepter antagonist, in anesthetized humans. Forty patients (four groups of 10 each) with ischemic heart disease and normal ventricular function were anesthetized with diazepam, pancuronium, and N2O in O2. Esmolol was given by continuous infusion in cumulative doses of 1100 micrograms/kg (group 1), 2000 micrograms/kg (group 2), and 2700 micrograms/kg (group 3); a control group received no esmolol. Infusion of esmolol was begun 3 min prior to and ended 4 min after tracheal intubation. All three doses of esmolol significantly (P less than 0.001) attenuated the heart rate responses to intubation. Rate-pressure products were significantly (P less than 0.001) lower in esmolol-treated patients than in controls after intubation, but ST-segment changes compatible with ischemia occurred in one patient in each group. Increases in heart rate were associated with significant increases in plasma norepinephrine levels (r = 0.45, P = 0.02) in the control group, but not in esmolol-treated patients, a demonstration that esmolol antagonizes the beta-adrenergic effects of norepinephrine. The effect of esmolol on heart rate was absent 5 min after cessation of infusion, and plasma levels of esmolol were undetectable in 26 of 30 treated patients 15 min after the termination of esmolol infusion. Esmolol has a rapid onset and short duration of effect. It can be used safely during anesthesia in patients with normal ventricular function to attenuate cardiac response to sympathetic stimulation.

Adrenergic beta-Antagonists↗
PubMed1985

Morphine--caffeine analgesic interaction in rats.

The ability of caffeine to modify the effect of morphine on motor response to noxious stimulation was studied in 195 rat experiments. Motor reaction responses to noxious stimuli were studied in three series of experiments with three different techniques of mechanical tail stimulation. In each series of experiments, dose-response curves for morphine (probit analysis) were determined with and without the addition of caffeine (30 mg X kg-1). It was found that caffeine decreased morphine ED50 values in all three series of experiments, from 1.1 to 0.6 mg X kg-1 (P less than 0.002), from 3.2 to 2.5 mg X kg-1 (P less than 0.01), and from 13.2 to 6.2 mg X kg-1 (P less than 0.002). When caffeine was used alone in a dose of 30 mg X kg-1, there were no significant changes in motor reaction responses with any of the three methods applied for the assessment of morphine-caffeine combinations. These data indicate that caffeine potentiates the inhibitory effect of morphine on motor response to noxious stimulation in rats. It has been suggested that the effect of morphine on the motor response to somatic noxious stimulation results primarily from activation of inhibitory control systems concerned with this response. Caffeine may modulate the antinociceptive effect of morphine by stimulating one of these systems.

Analgesics↗
PubMed1984

Morphine-halothane interaction in rats.

The effects of morphine, halothane, and their various combinations on the purposeful movement (PM) response and the heart rate (HR) increase caused by noxious stimulation were studied in 250 rat experiments. Doses that block the PM and HR responses for the single agent and for combinations were determined with a probit procedure and compared with an isobolographic analysis. As was evidenced by the PM response, the combined anesthetic effect of morphine and halothane, with some deviations, may be defined as additive. It also was found that the combined administration of morphine and halothane results in an antagonism for suppression of the HR increase to noxious stimulation. Halothane antagonized morphine to a much greater extent than morphine to halothane.

Animals↗
PubMed1984

Halothane antagonizes effect of morphine on the motor reaction threshold in rats.

The ability of halothane (used in "sub-MAC" concentrations) to modify the effect of morphine on motor response threshold to pressure was studied and compared with pentobarbital in 241 rat experiments. It was found that halothane (0.5-0.7%, insp.) decreased the reaction threshold to pressure, as did pentobarbital. Halothane (0.5%) increased morphine ED50 for the reaction threshold to pressure from 0.21 mg . kg-1 (95% fiducial limits: 0.13-0.29 mg . kg-1) to 0.52 mg . kg-1 (0.28-0.73 mg . kg-1, P less than 0.0001). Pentobarbital in a dose of 3 mg . kg-1 demonstrated a similar antanalgesic effect. Neither halothane nor pentobarbital antagonized the effect of morphine with motor response to the tail clamp. On the contrary, both agents strengthened this effect. It has been suggested that the effect of morphine on the motor response threshold to pressure results primarily from activation of inhibitory control mechanisms concerned with this response; halothane in a subanesthetic concentration depresses the inhibitory control mechanisms and, therefore, weakens the effect of morphine.

Animals↗