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1.
J Clin Med ; 11(19)2022 Sep 23.
Article in English | MEDLINE | ID: mdl-36233454

ABSTRACT

Fentanyl and short-acting remifentanil are often used in combination. We evaluated the effect of intraoperative opioid administration on postoperative pain and pain thresholds when the two drugs were used. Patients who underwent gynecological laparoscopic surgery were randomly assigned into two groups (15 patients each) to receive either sufficient (group A) or minimum (group B) fentanyl (maximum estimated effect site concentration: A: 7.86 ng/mL, B: 1.5 ng/mL). The estimated effect site concentration at the end of surgery was adjusted to the same level (1 ng/mL). Patients in both groups also received continuous intravenous remifentanil during surgery. The primary outcome was the pressure pain threshold, as evaluated by a pressure algometer 3 h postoperatively. The pressure pain threshold at 3 h postoperatively was 51.1% (95% CI: [44.4-57.8]) in group A and 56.6% [49.5-63.6] in group B, assuming a preoperative value of 100% (p = 0.298). There were no significant differences in pressure pain threshold and numeric rating scale scores between the groups after surgery. The pain threshold decreased significantly in both groups at 3 h postoperatively compared to preoperative values, and recovered at 24 h. Co-administration of both opioids caused hyperalgesia regardless of fentanyl dose.

2.
Anesthesiology ; 128(5): 992-1003, 2018 05.
Article in English | MEDLINE | ID: mdl-29521652

ABSTRACT

BACKGROUND: Sleepiness and decrease in attention are dose-limiting side effects of opioids. The orexin/hypocretin system plays an important role in maintaining wakefulness. This study aimed to explore the potential of a nonpeptide orexin receptor agonist to alleviate morphine-induced sedative effects. METHODS: Morphine sedative effects were evaluated as changes in electroencephalogram (EEG), locomotor activity, and acoustic startle response in rats (n = 5 to 9 per group). Effects of intracerebroventricular orexin-A and systemic orexin type-2 receptor agonist, YNT-185, on EEG changes induced by morphine were examined. Furthermore, the authors examined effects of morphine administered with or without YNT-185 on locomotor activity and on acoustic startle response. RESULTS: Morphine-induced, frequent, short epochs of increased power (total epoch duration: 0.5 [0.0 to 8.0] s/10 min during baseline vs. 74.0 [49.0 to 115.0] s/10 min during the post-morphine administration period; P = 0.012). EEG analyses revealed that morphine-induced, high-amplitude, slow activity (increase in spectral power of frequencies less than 15 Hz, baseline vs. postmorphine; P < 0.001). Orexin-A and YNT-185 attenuated these changes. Locomotor activity decreased after morphine (268 [103 to 889] ambulatory movement counts during baseline period [20 min] vs. 138 [7 to 434] counts during 40 to 59 min postadministration; P = 0.012), but did not change after morphine with YNT-185 (363 [121 to 636] vs. 864 [381 to 1092] counts, difference within morphine + YNT-185 group; P = 0.071). Startle response latency was longer after morphine (26 [20 to 28] ms) than after morphine with YNT-185 (17 [16 to 18] ms; P = 0.012). CONCLUSIONS: Orexin-A and/or YNT-185 attenuated morphine-induced sedative effects assessed by EEG changes and behavioral measures in rats. The authors' results suggest that orexin-2 receptor activation alleviates morphine-induced sedative effects.


Subject(s)
Morphine/pharmacology , Orexin Receptors/agonists , Aniline Compounds/pharmacology , Animals , Benzamides/pharmacology , Dose-Response Relationship, Drug , Electroencephalography/drug effects , Hypnotics and Sedatives/pharmacology , Male , Morphine/adverse effects , Motor Activity/drug effects , Orexin Receptors/physiology , Orexins/pharmacology , Rats , Rats, Sprague-Dawley , Reflex, Startle/drug effects , Respiration/drug effects
4.
Pharmacology ; 89(3-4): 145-8, 2012.
Article in English | MEDLINE | ID: mdl-22414674

ABSTRACT

BACKGROUND/AIMS: Multiple opioid receptor (OR) types and endogenous opioid peptides exist in the spinal dorsal horn and there may be interactions among these receptor types that involve opioid peptides. In a previous study we observed that antinociceptive effects of the selective κ-opioid receptor (κOR) agonist, U50,488H, was attenuated in µ-opioid receptor (µOR) knockout mice as compared to wild-type mice when administered spinally. This suggests that an interaction between κORs and µORs exits in the spinal cord. The present study was aimed at investigating whether endogenous opioid peptides were involved in such interaction. METHODS: We examined whether the presence of antibodies to endogenous opioid peptides, endomorphin-2, met-enkephalin and dynorphin A affected the antinociceptive effects of spinal U50,488H in rats. The tail-flick test was used to assess pain thresholds. RESULTS: The increase in tail-flick latency after spinal U50,488H was attenuated when the rats were pretreated intrathecally with antiserum against endomorphin-2. Pretreatments with antisera against met-enkephalin and dynorphin A had no effect on U50,488H antinociception. The antisera alone did not affect pain threshold. CONCLUSION: The results suggest that endomorphin-2, an endogenous opioid peptide highly selective to the µOR, plays a role in antinociception induced by κOR activation in the spinal cord.


Subject(s)
Oligopeptides/physiology , Pain/physiopathology , Receptors, Opioid, kappa/physiology , Spinal Cord/physiology , 3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer/therapeutic use , Analgesics, Non-Narcotic/therapeutic use , Animals , Dynorphins/physiology , Enkephalin, Methionine/physiology , Male , Pain/drug therapy , Rats , Rats, Sprague-Dawley , Receptors, Opioid, mu/physiology
5.
Anesthesiology ; 113(4): 812-8, 2010 Oct.
Article in English | MEDLINE | ID: mdl-20823756

ABSTRACT

BACKGROUND: Obstructive sleep apnea (OSA) is an independent risk factor for difficult and/or impossible mask ventilation during anesthesia induction. Postural change from supine to sitting improves nocturnal breathing in patients with OSA. The purpose of this study was to evaluate the effect of patient position on collapsibility of the pharyngeal airway in anesthetized and paralyzed patients with OSA. The authors tested the hypothesis that the passive pharynx is structurally less collapsible during sitting than during supine posture. METHOD: Total muscle paralysis was induced with general anesthesia in nine patients with OSA, eliminating neuromuscular factors contributing to pharyngeal patency. The cross-sectional area of the pharynx was measured endoscopically at different static airway pressures. Comparison of static pressure-area plots between the supine and sitting (62° head-up) allowed assessment of the postural differences of the mechanical properties of the pharynx. RESULTS: : Maximum cross-sectional area was greater during sitting than during supine posture at both retropalatal (median (10th-90th percentile): 1.91 (1.52-3.40) versus 1.25 (0.65-1.97) cm) and retroglossal (2.42 (1.72-3.84) versus 1.75 (0.47-2.35) cm) airways. Closing pressure of the passive pharynx was significantly lower during sitting than supine posture. Differences of the closing pressures between the postures are 5.89 (3.73-11.6) and 6.74 (4.16-9.87) cm H2O, at retropalatal and retroglossal airways, respectively, and did not differ between the pharyngeal segments. CONCLUSIONS: Postural change from supine to sitting significantly improves collapsibility of pharyngeal airway in anesthetized and paralyzed patients with OSA.


Subject(s)
Anesthesia, General , Pharynx/anatomy & histology , Posture/physiology , Sleep Apnea, Obstructive/physiopathology , Sleep Apnea, Obstructive/surgery , Adult , Anatomy, Cross-Sectional , Biomechanical Phenomena , Humans , Male , Middle Aged , Palate/surgery , Paralysis/chemically induced , Paralysis/physiopathology , Pharynx/surgery , Pressure , Uvula/surgery
6.
Pharmacology ; 83(1): 33-7, 2009.
Article in English | MEDLINE | ID: mdl-18987489

ABSTRACT

AIMS: H-Dmt-D-Arg-Phe-Lys-NH(2) ([Dmt(1)]DALDA), a highly selective micro-opioid peptide, is potently analgesic after systemic and intrathecal administration but is less potent given intracerebroventricularly. This study was performed to further characterize the analgesic effects of [Dmt(1)]DALDA. METHODS: We compared the effects of [Dmt(1)]DALDA and morphine after systemic administration in two different acute pain tests, the tail flick test and the paw withdrawal test, and examined how antagonizing the spinal opioid actions would affect their analgesic effects. RESULTS: [Dmt(1)]DALDA was markedly more potent in the tail flick test than in the hot plate test, while the potencies of morphine were similar in the two tests. Intrathecal naloxone completely blocked the effect of systemic [Dmt(1)]DALDA in the tail flick test, while it only partially blocked the effect of morphine. At higher doses that produced analgesia in the hot plate test, the effect of [Dmt(1)]DALDA in this test was only partially blocked by naloxone. CONCLUSION: Systemic [Dmt(1)]DALDA has a unique analgesic property clearly different from that of morphine and it has a propensity to produce spinal analgesia.


Subject(s)
Analgesics, Opioid/pharmacology , Oligopeptides/pharmacology , Pain/drug therapy , Receptors, Opioid, mu/agonists , Analgesics, Opioid/administration & dosage , Animals , Disease Models, Animal , Dose-Response Relationship, Drug , Injections, Spinal , Male , Morphine/administration & dosage , Morphine/pharmacology , Naloxone/pharmacology , Narcotic Antagonists/pharmacology , Oligopeptides/administration & dosage , Pain Measurement , Rats , Rats, Sprague-Dawley
7.
J Appl Physiol (1985) ; 103(4): 1379-85, 2007 Oct.
Article in English | MEDLINE | ID: mdl-17600160

ABSTRACT

Lung volume dependence of pharyngeal airway patency suggests involvement of lung volume in pathogenesis of obstructive sleep apnea. We examined the structural interaction between passive pharyngeal airway and lung volume independent of neuromuscular factors. Static mechanical properties of the passive pharynx were compared before and during lung inflation in eight anesthetized and paralyzed patients with sleep-disordered breathing. The respiratory system volume was increased by applying negative extrathoracic pressure, thereby leaving the transpharyngeal pressure unchanged. Application of -50-cmH(2)O negative extrathoracic pressure produced an increase in lung volume of 0.72 (0.63-0.91) liter [median (25-75 percentile)], resulting in a significant reduction of velopharyngeal closing pressure of 1.22 (0.14-2.03) cmH(2)O without significantly changing collapsibility of the oropharyngeal airway. Improvement of the velopharyngeal closing pressure was directly associated with body mass index. We conclude that increase in lung volume structurally improves velopharyngeal collapsibility particularly in obese patients with sleep-disordered breathing.


Subject(s)
Lung/physiopathology , Pharynx/physiopathology , Sleep Apnea, Obstructive/physiopathology , Humans , Inspiratory Capacity , Lung Volume Measurements , Obesity/complications , Obesity/etiology , Obesity/physiopathology , Respiration
8.
Anesth Analg ; 101(6): 1615-1618, 2005 Dec.
Article in English | MEDLINE | ID: mdl-16301229

ABSTRACT

To investigate how sevoflurane modifies airway protective reflexes in anesthetized children, we recruited patients younger than 12-yr-old for our study. Anesthesia was induced with inhaled sevoflurane in oxygen. The airway was managed with a laryngeal mask airway and the patient breathing spontaneously. Depending on the depth of anesthesia, the subjects were divided into two groups: Group 1 and Group 2 (1% and 2% of end-tidal sevoflurane concentration, respectively). Behaviors of the larynx were assessed mainly by the fiberscopic images of the larynx as well as respiratory flow and esophageal pressure. A small dose, 0.02 mL/kg of distilled water (minimum 0.2 mL) was instilled to the larynx through a channel of the scope to evoke an airway protective reflex from the larynx. The responses were categorized into passive (laryngeal closure, laryngospasm, and apnea) and active (cough, expiration reflex, and swallowing reflex) responses. Ten subjects were included in each group. In both groups, the primary responses were passive; however, in Group 1, active reflexes were also observed in 8 of 10 subjects; no subjects in Group 2 had active reflexes (P < 0.01). We concluded that, in children, the depth of general anesthesia with sevoflurane modified airway protective reflexes.


Subject(s)
Anesthesia, General , Anesthetics, Inhalation/pharmacology , Laryngeal Masks , Larynx/physiology , Methyl Ethers/pharmacology , Reflex/drug effects , Child , Child, Preschool , Humans , Infant , Sevoflurane , Water
9.
Anesthesiology ; 103(3): 489-94, 2005 Sep.
Article in English | MEDLINE | ID: mdl-16129972

ABSTRACT

BACKGROUND: Appropriate bag-and-mask ventilation with patent airway is mandatory during induction of general anesthesia. Although the sniffing neck position is a traditionally recommended head and neck position during this critical period, knowledge of the influences of this position on the pharyngeal airway patency is still inadequate. METHODS: Total muscle paralysis was induced with general anesthesia in 12 patients with obstructive sleep apnea, eliminating neuromuscular factors contributing to pharyngeal patency. The cross-sectional area of the pharynx was measured endoscopically at different static airway pressures. Comparison of static pressure-area plot between the neutral and sniffing neck positions allowed assessment of the influence of the neck position change on the mechanical properties of the pharynx. RESULTS: The static pressure-area curves of the sniffing position were above those of neutral neck position, with increasing maximum cross-sectional area and decreasing the closing pressure at both retropalatal and retroglossal airways. The beneficial effects of the sniffing position were greater in obstructive sleep apnea patients with higher closing pressure and smaller body mass index. CONCLUSIONS: Sniffing position structurally improves maintenance of the passive pharyngeal airway in patients with obstructive sleep apnea and may be beneficial for both mask ventilation and tracheal intubation during anesthesia induction.


Subject(s)
Anesthesia , Pharynx/physiology , Posture , Sleep Apnea, Obstructive/physiopathology , Adult , Aged , Humans , Intubation, Intratracheal , Middle Aged , Neck , Respiratory Mechanics
10.
J Appl Physiol (1985) ; 99(3): 807-13, 2005 Sep.
Article in English | MEDLINE | ID: mdl-15890760

ABSTRACT

Heart rate variability (HRV) is a well-characterized, noninvasive means of assessing cardiac autonomic nervous system activity. This study examines the basic cardiac responses to hypoxic and hypercapnic challenges in seven strains of commonly used inbred mice (A/J, BALB/cJ, C3H/HeJ, C57BL/6J, CBA/J, DBA/2J, and FVB/J). Adult male mice, 8-12 wk of age, were chronically instrumented to a femoral artery catheter for the continuous measurement of systemic arterial blood pressure and heart rate. Mice were exposed to multiple 4-min periods of hypoxia (10% O2), hypercapnia (5% CO2), and combined hypoxia/hypercapnia (10% O2 + 5% CO2). HRV was derived from pulse intervals of the blood pressure tracings. Hypoxia induced increases in high-frequency HRV power and decreased low-frequency (LF) HRV power in most strains. Hypercapnia led to decreased high-frequency HRV power and increased LF HRV power in most strains. Strain differences were most notable in regard to the concomitant exposures of hypoxia and hypercapnia, with FVB/J mice mirroring their own response to hypercapnia alone, whereas CBA/J mice mirrored their own responses to hypoxia. As blood pressure is most likely the driving factor for heart rate changes via the baroreflex pathway, it is interesting that LF, considered to reflect cardiac sympathetic activity, was negatively correlated with heart rate, suggesting that LF changes are driven by baroreflex oscillation and not necessarily by absolute sympathetic or parasympathetic activity to the heart. These findings suggest that genetic background can influence the centrally mediated cardiovascular responses to basic hypoxic and hypercapnic challenges.


Subject(s)
Blood Pressure , Heart Rate , Hypercapnia/physiopathology , Hypoxia/physiopathology , Animals , Hypercapnia/complications , Hypoxia/complications , Male , Mice , Species Specificity
11.
Physiol Genomics ; 20(1): 15-20, 2004 Dec 15.
Article in English | MEDLINE | ID: mdl-15494473

ABSTRACT

The impact of genetic variation on cardiovascular responses to hypoxia and hypercapnia is not well understood. Therefore, we determined the acute changes in systemic arterial blood pressure (P(SA)) and heart rate (HR) in seven strains of commonly used inbred mice exposed to acute periods of hypoxia (10% O(2)), hypercapnia (5% CO(2)), and hypoxia/hypercapnia (10% O(2) + 5% CO(2)) during wakefulness. Hypercapnia induced an essentially homogeneous response across strains, with P(SA) maintained at or slightly above baseline and with HR exhibiting a typical baroreceptor-mediated bradycardia. In contrast, exposure to hypoxia elicited a marked heterogeneity in cardiovascular responses between strains. The change in P(SA) during hypoxia ranged from maintenance of normotension in the FVB/J strain to profound hypotension of approximately 30 mmHg in the DBA/2J strain. HR responses were highly variable between strains during hypoxia, and with the exception of the DBA/2J strain that exhibited significant bradyarrhythmias and consequent hypotension, the HR responses were unrelated to changes in P(SA). The P(SA) response to combined hypoxia/hypercapnia represented a balance of the hypertension of hypercapnia and the hypotension of hypoxia in six of the seven strains. In the FVB/J strain, combined hypoxia/hypercapnia produced a hypertensive response that was greater than that of hypercapnia alone. These results suggest that genetic background affects the cardiovascular response to hypoxia, but not hypercapnia.


Subject(s)
Cardiovascular System , Genetic Variation , Hypoxia , Analysis of Variance , Animals , Arrhythmias, Cardiac , Blood Pressure , Bradycardia/metabolism , Heart Rate , Hypercapnia , Hypotension , Male , Mice , Mice, Inbred BALB C , Mice, Inbred C3H , Mice, Inbred C57BL , Mice, Inbred DBA , Muridae , Oxygen/metabolism , Phenotype , Species Specificity , Temperature
12.
J Appl Physiol (1985) ; 97(1): 339-46, 2004 Jul.
Article in English | MEDLINE | ID: mdl-15020573

ABSTRACT

A collapsible tube surrounded by soft material within a rigid box was proposed as a two-dimensional mechanical model for the pharyngeal airway. This model predicts that changes in the box size (pharyngeal bony enclosure size anatomically defined as cross-sectional area bounded by the inside edge of bony structures such as the mandible, maxilla, and spine, and being perpendicular to the airway) influence patency of the tube. We examined whether changes in the bony enclosure size either with head positioning or bite opening influence collapsibility of the pharyngeal airway. Static mechanical properties of the passive pharynx were evaluated in anesthetized, paralyzed patients with sleep-disordered breathing before and during neck extension with bite closure (n = 11), neck flexion with bite closure (n = 9), and neutral neck position with bite opening (n = 11). Neck extension significantly increased maximum oropharyngeal airway size and decreased closing pressures of the velopharynx and oropharynx. Notably, neck extension significantly decreased compliance of the oropharyngeal airway wall. Neck flexion and bite opening decreased maximum oropharyngeal airway size and increased closing pressure of the velopharynx and oropharynx. Our results indicate the importance of neck and mandibular position for determining patency and collapsibility of the passive pharynx.


Subject(s)
Head/physiology , Jaw/physiology , Pharynx/physiology , Posture/physiology , Adult , Anesthesia , Biomechanical Phenomena , Humans , Lung Compliance/physiology , Male , Middle Aged , Models, Anatomic , Neck/anatomy & histology , Neck/physiology , Oropharynx/anatomy & histology , Oropharynx/physiology , Oximetry , Paralysis/chemically induced , Paralysis/physiopathology , Pharynx/anatomy & histology , Sleep Apnea Syndromes/pathology , Sleep Apnea Syndromes/physiopathology , Supine Position/physiology
13.
Respir Physiol Neurobiol ; 136(1): 55-63, 2003 Jun 12.
Article in English | MEDLINE | ID: mdl-12809798

ABSTRACT

Short-term chest compression has been shown to decrease tidal volume and increase respiratory frequency. The present study was designed to assess and characterize the effect of long-term chest compression on breathing pattern and blood gases in awake rats. Chest compression was carried out by inflating a pneumatic cuff placed around the chest to a pressure of 25 mmHg and the pressure was maintained for 28 days. Respiratory frequency increased progressively until 14 days after chest compression whereas a decrease in tidal volume was stabilized within 3 days after chest compression. Although the changes in minute ventilation were small and no substantial change in Pa(CO2) was observed, an impairment of weight gain and a decrease in body temperature with a concomitant hypoxemia were evident during sustained chest compression. These observations suggest that the ventilatory response to chest compression may involve not only neural reflex mechanisms but also other non-reflex mechanisms. Sustained chest compression possibly impairs growth and metabolism.


Subject(s)
Consciousness/physiology , Models, Animal , Pulmonary Ventilation/physiology , Respiration, Artificial , Respiratory Mechanics/physiology , Animals , Blood Gas Analysis/methods , Body Temperature/physiology , Body Weight/physiology , Eating/physiology , Male , Rats , Rats, Sprague-Dawley , Respiratory Function Tests , Respiratory Physiological Phenomena , Time Factors
14.
Physiol Genomics ; 11(3): 227-34, 2002 Dec 03.
Article in English | MEDLINE | ID: mdl-12388788

ABSTRACT

The pattern of cardiovascular changes that occur at nighttime can have an impact on morbidity and mortality. Rapid-eye-movement (REM) sleep, in particular, represents a period of increased risk due to marked cardiovascular instability. We hypothesized that genetic differences between inbred strains of mice would affect the phenotypic expression of cardiovascular responses that occur in REM sleep. We monitored polysomnography and arterial blood pressure (P(SA)) simultaneously in six inbred strains of mice as they naturally cycled through sleep/wake states. Two strains elevated their P(SA) above non-REM (NREM) levels for 57.9 +/- 6.6% (BALB/cJ) and 51.8 +/- 8.4% (DBA/2J) of the REM period and exhibited a significant (P < 0.05) number of P(SA) surges greater than 10 mmHg (0.78 +/- 0.36 surges/min for BALB/cJ; 0.63 +/- 0.13 surges/min for DBA/2J). Despite similar P(SA) responses, the DBA/2J strain exhibited a decreased heart rate and the BALB/cJ strain exhibited an increased heart rate during REM sleep. The four other strains (A/J, C57BL/6J, C3H/HeJ, and CBA/J) exhibited a significant hypotensive response associated with no change in heart rate in three of the strains and a significant decrease in heart rate in the A/J strain. The overall variability in P(SA) during REM sleep was significantly greater in the C3H/HeJ strain (26.8 +/- 2.0 mmHg; P < 0.0125) compared with the other five strains. We conclude that genetic background contributes to the magnitude, variability, and arterial baroreceptor buffering capacity of cardiovascular responses during REM sleep.


Subject(s)
Hemodynamics/genetics , Sleep, REM , Animals , Blood Pressure , Blood Vessels/innervation , Genetic Variation , Heart/innervation , Heart Rate , Kinetics , Male , Mice , Mice, Inbred BALB C , Mice, Inbred C3H , Mice, Inbred C57BL , Mice, Inbred CBA , Mice, Inbred DBA , Mice, Inbred Strains , Neural Pathways , Neurotransmitter Agents/physiology , Phenotype , Polysomnography , Species Specificity
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