rocuronium and Disease-Models--Animal

There are a few reports in the literature about the successful use of sugammadex in the treatment of hypersensitivity reactions caused by rocuronium; however, the pathophysiological mechanism is still unknown. This study aims to investigate the changes caused by rocuronium in the lung and the effect of sugammadex on these changes with biochemical, light microscopic and immunohistochemical parameters on a rat model.. For the study, 28-male Sprague-Dawley rats were randomly divided, seven of each, into four groups. Group C (control) received only 0. 9 % NaCl without any drug. Group R received rocuronium alone 1mg/kg. Group S received sugammadex alone 96 mg/kg. Group RS received rocuronium 1mg/kg and sugammadex 96 mg/kg. After 24 h later, the animals were sacrificed and their tissues were removed. Biochemical (IgE/CRP), light microscopic and immunohistochemical findings were recorded.. Immunoglobulin E and CRP levels, peribronchial, alveolar septal lymphocytic infiltration, thickening of the alveolar membranes and bleeding sites in Group R were significantly higher than all the other groups. In Group RS, while these parameters were significantly lower than that of Group R and Group S, it was significantly higher than that of Group C. Total mast cells and tryptase-positive mast cells counts were significantly higher in Group R than in all other groups. In Group RS, these parameters were statistically lower than that of Group R and Group S, but higher than that of Group C.. This study shows that allergic inflammatory changes due to rocuronium in the lungs of rats are reduced with sugammadex. These results support cases of anaphylaxis due to rocuronium which improved with sugammadex.

Topics: Anaphylaxis; Animals; C-Reactive Protein; Disease Models, Animal; Hemorrhage; Hypersensitivity; Immunoglobulin E; Inflammation; Lung; Lymphocytes; Male; Mast Cells; Neuromuscular Nondepolarizing Agents; Pulmonary Alveoli; Random Allocation; Rats; Rats, Sprague-Dawley; Rocuronium; Sugammadex; Tryptases

The concentration range of dexamethasone that inhibits neuromuscular blockade (NMB) and sugammadex reversal remains unclear.. To evaluate the effects of dexamethasone on rocuronium-induced NMB and sugammadex reversal.. Ex vivo study.. Asan Institute for Life Sciences, Asan Medical Center, Korea, from July 2015 to November 2015.. One hundred sixty male Sprague-Dawley rats.. We assessed the effect of four concentrations of dexamethasone [0, 0.5, 5 (clinical concentrations) and 50 μg ml (experimental concentration)] on partial NMB on 40 phrenic nerve-hemidiaphragm preparations (n=10 per concentration). Once the first twitch of train-of-four (TOF) had been depressed by 50% with rocuronium, dexamethasone was administered. To assess the effect of dexamethasone on sugammadex reversal, 120 phrenic nerve-hemidiaphragm preparations were used in three subexperiments (n=40 per experiment), using three administration regimens of rocuronium-equimolar sugammadex: a single dose, a split-dose (split and ) and a reduced split-dose (split and ). After complete NMB was achieved, dexamethasone and sugammadex were administered.. The change in the first twitch height, the recovery time to a TOF ratio at least 0.9, and the TOF ratio at 30 min were evaluated.. There were no significant differences in the first twitch height among groups (P = 0.532). With a single dose of sugammadex, dexamethasone did not affect the recovery time to a TOF ratio at least 0.9 (P = 0.070). After using a split-dose of sugammadex, the recovery time to a TOF ratio at least 0.9 was delayed only at a concentration of 50 μg ml of dexamethasone. With a reduced split-dose of sugammadex, the TOF ratio at 30 min was lowered only by a concentration of 50 μg ml of dexamethasone (P < 0.010).. Acute bolus administration of dexamethasone at clinical concentrations had no effect on NMB or on sugammadex reversal.

Topics: Animals; Antiemetics; Delayed Emergence from Anesthesia; Dexamethasone; Diaphragm; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Interactions; Humans; Male; Neuromuscular Blockade; Neuromuscular Monitoring; Neuromuscular Nondepolarizing Agents; Phrenic Nerve; Postoperative Nausea and Vomiting; Rats; Rats, Sprague-Dawley; Rocuronium; Sugammadex; Time Factors

Carbon monoxide (CO) poisoning is a common cause of poison-related mortality. CO binds to hemoglobin in the blood to form carboxyhemoglobin (COHb), impairing oxygen delivery to peripheral tissues. Current treatment of CO-poisoned patients involves oxygen administration to rapidly remove CO and restore oxygen delivery. Light dissociates CO from COHb with high efficiency. Exposure of murine lungs to visible laser-generated light improved the CO elimination rate in vivo. The aims of this study were to apply pulmonary phototherapy to a larger animal model of CO poisoning, to test novel approaches to light delivery, and to examine the effect of chemiluminescence-generated light on the CO elimination rate.. Anesthetized and mechanically ventilated rats were poisoned with CO and subsequently treated with air or oxygen combined with or without pulmonary phototherapy delivered directly to the lungs of animals at thoracotomy, via intrapleural optical fibers or generated by a chemiluminescent reaction.. Direct pulmonary phototherapy dissociated CO from COHb reducing COHb half-life by 38%. Early treatment with phototherapy in critically CO poisoned rats improved lactate clearance. Light delivered to the lungs of rats via intrapleural optical fibers increased the rate of CO elimination without requiring a thoracotomy, as demonstrated by a 16% reduction in COHb half-life. Light generated in the pleural spaces by a chemiluminescent reaction increased the rate of CO elimination in rats breathing oxygen, reducing the COHb half-life by 12%.. Successful application of pulmonary phototherapy in larger animals and humans may represent a significant advance in the treatment of CO-poisoned patients.

Topics: Androstanols; Animals; Blood Pressure; Body Temperature; Carbon Monoxide; Carbon Monoxide Poisoning; Carotid Arteries; Disease Models, Animal; Fentanyl; Heart Rate; Hemoglobins; Injections, Intraperitoneal; Ketamine; Luminescence; Male; Phototherapy; Rats; Rats, Sprague-Dawley; Rocuronium; Tracheotomy

Train-of-four ratio (TOFR) is often used to evaluate muscle relaxation caused by neuromuscular-blocking agents (NMBAs). However, it is unknown whether TOFR reliably correlates with the first twitch tension (T1) in patients with myasthenia gravis (MG). By using rat models of experimental autoimmune MG (EAMG), the authors verified the hypothesis that the severity of MG influences the relationship between TOFR and T1.. EAMG rats were divided into sham, moderate MG, and severe MG groups. Isometric twitch tension of the hemidiaphragm was elicited by phrenic nerve stimulation with and without use of the NMBA rocuronium to measure TOFR and T1, and run-down of endplate potentials was estimated in the three groups. Changes around the neuromuscular junction in EAMG rats were investigated by observation of electron micrographs.. With similar attenuation of T1, TOFR was significantly (n = 6) different among the three groups in the presence of 50% inhibitory concentrations of rocuronium (IC50). Run-down in the sham group was significantly (n = 8) greater with exposure to IC50, whereas that in the severe MG group was statistically insignificant. Width of the primary synaptic cleft in the severe MG group was significantly (n = 80) greater than that in the other groups.. Severity of MG influences the relationship between TOFR and T1, together with changes in run-down of endplate potentials and those around the neuromuscular junction in rats. TOFR may, therefore, not be an accurate indicator of recovery from NMBAs in MG patients.

Topics: Androstanols; Animals; Diaphragm; Disease Models, Animal; Excitatory Postsynaptic Potentials; Female; Myasthenia Gravis; Neuromuscular Junction; Neuromuscular Monitoring; Neuromuscular Nondepolarizing Agents; Rats; Rats, Inbred Lew; Rocuronium; Severity of Illness Index; Synaptic Transmission

The antagonistic actions of anticholinesterase drugs on non-depolarizing muscle relaxants are theoretically related to the activity of acetylcholinesterase (AChE) in the neuromuscular junction (NMJ). However, till date the changes of AChE activity in the NMJ during sepsis have not been directly investigated. We aimed to investigate the effects of sepsis on the antagonistic actions of neostigmine on rocuronium (Roc) and the underlying changes of AChE activity in the NMJ in a rat model of cecal ligation and puncture (CLP).. A total of 28 male adult Sprague-Dawley rats were randomized to undergo a sham surgery (the sham group, n = 12) or CLP (the septic group, n = 16). After 24 h, the time-response curves of the antagonistic actions of 0.1 or 0.5 μmol/L of neostigmine on Roc (10 μmol/L)-depressed diaphragm twitch tension were measured. Meanwhile, the activity of AChE in the NMJ was detected using a modified Karnovsky and Roots method. The mRNA levels of the primary transcript and the type T transcript of AChE (AChET) in the diaphragm were determined by real-time reverse transcription-polymerase chain reaction.. Four of 16 rats in the septic group died within 24 h. The time-response curves of both two concentrations of neostigmine in the septic group showed significant upward shifts from those in the sham group (P < 0.001 for 0.1 μmol/L; P = 0.009 for 0.5 μmol/L). Meanwhile, the average optical density of AChE in the NMJ in the septic group was significantly lower than that in the sham group (0.517 ± 0.045 vs. 1.047 ± 0.087, P < 0.001). The AChE and AChETmRNA expression levels in the septic group were significantly lower than those in the sham group (P = 0.002 for AChE; P = 0.001 for AChET).. Sepsis strengthened the antagonistic actions of neostigmine on Roc-depressed twitch tension of the diaphragm by inhibiting the activity of AChE in the NMJ. The reduced content of AChE might be one of the possible causes of the decreased AChE activity in the NMJ.

Topics: Acetylcholinesterase; Androstanols; Animals; Cecum; Cholinesterase Inhibitors; Diaphragm; Disease Models, Animal; Ligation; Male; Neostigmine; Neuromuscular Junction; Neuromuscular Nondepolarizing Agents; Punctures; Random Allocation; Rats; Rats, Sprague-Dawley; Rocuronium; Sepsis

Compare the onset and duration of rocuronium administered via the intravenous (IV), and intraosseous (IO) routes in a hypovolemic swine model.. Prospective, between subjects, experimental study.. Vivarium.. Yorkshire-cross swine (N = 8).. Electromyography (EMG) amplitudes were recorded at baseline and for every 15 seconds after administering 1.2 mg/kg of rocuronium via IV or IO routes to hypovolemic swine. EMG amplitudes were measured until termination of EMG activity and then measured every 5 minutes until there was a return to baseline values. Individual data were transformed to percent baseline.. The time from the end of injection to 90 percent reduction of baseline EMG activity (Onset. Maximum reduction, Onset 90 and Onset peak times were not statistically different between groups. The IV group's mean time to recovery of all benchmarks was faster than the IO group. The IO group took statistically longer than the IV group to return to 25, 50, 75, and 95 percent of baseline activity.. The IO route is an effective method of administering rocuronium and is comparable to the IV route even under conditions of significant hemorrhage.

Topics: Androstanols; Animals; Cardiopulmonary Resuscitation; Chromatography, High Pressure Liquid; Disease Models, Animal; Electromyography; Heart Arrest; Hypovolemia; Infusions, Intraosseous; Infusions, Intravenous; Prospective Studies; Random Allocation; Rocuronium; Swine; Tandem Mass Spectrometry

Muscles innervated by the facial nerve show differential sensitivities to muscle relaxants than muscles innervated by somatic nerves. The evoked electromyography (EEMG) response is also proportionally reduced after facial nerve injury. This forms the theoretical basis for proper utilization of muscle relaxants to balance EEMG monitoring and immobility under general anesthesia. (1) To observe the relationships between the level and mode of acetylcholine (ACh) release and the duration of facial nerve injury, and the influence of rocuronium in an in vitro rabbit model. (2) To explore the pre-synaptic mechanisms of discrepant responses to a muscle relaxant. Quantal and non-quantal ACh release were measured by using intracellular microelectrode recording in the orbicularis oris 1 to 42 days after graded facial nerve injury and in the gastrocnemius with/without rocuronium. Quantal ACh release was significantly decreased by rocuronium in the orbicularis oris and gastrocnemius, but significantly more so in gastrocnemius. Quantal release was reduced after facial nerve injury, which was significantly correlated with the severity of nerve injury in the absence but not in the presence of rocuronium. Non-quantal ACh release was reduced after facial nerve injury, with many relationships observed depending on the extent of the injury. The extent of inhibition of non-quantal release by rocuronium correlated with the grade of facial nerve injury. These findings may explain why EEMG amplitude might be diminished after acute facial nerve injury but relatively preserved after chronic injury and differential responses in sensitivity to rocuronium.

Topics: Acetylcholine; Androstanols; Animals; Disease Models, Animal; Electromyography; Facial Nerve; Facial Nerve Injuries; Male; Microelectrodes; Muscle, Skeletal; Neuromuscular Junction; Neuromuscular Nondepolarizing Agents; Rabbits; Rocuronium; Tibial Nerve

The aim of this study was to elucidate the influence of four neuromuscular blocking substances on coronary vascular tone using the model of isolated porcine coronary artery segments. We studied the effects of four muscle relaxants, atracurium, pancuronium, rocuronium, and vecuronium (0.1, 1, and 10 microg mL-1 each), on the contractile response to three vasoconstrictors: acetylcholine, histamine, and serotonin. None of the neuromuscular blocking agents under investigation exerted a significant influence on the vasoconstricting effects of these mediators except for pancuronium, which dose-dependently attenuated acetylcholine-mediated contractions (-10.8% attenuation for 10 microg mL-1 pancuronium, P < 0.05). There was no difference between vessels with intact endothelium and denuded preparations. It is concluded that high-dose pancuronium exerts an antimuscarinic effect in vascular smooth muscle. The other neuromuscular agents studied do not alter vascular reactivity of isolated porcine coronary arteries.

Topics: Acetylcholine; Androstanols; Animals; Atracurium; Coronary Vessels; Disease Models, Animal; Dose-Response Relationship, Drug; Endothelium, Vascular; Histamine; Muscarinic Antagonists; Muscle, Smooth, Vascular; Neuromuscular Nondepolarizing Agents; Pancuronium; Rocuronium; Serotonin; Statistics as Topic; Swine; Vasoconstriction; Vasoconstrictor Agents; Vasodilator Agents; Vecuronium Bromide