Suppression of arterial pressure, heart rate and cardiac contractility following microinjection of kainic acid into the nucleus ambiguus of the rat

Objective: This study aims to investigate the effect of dexmedetomidine on perioperative stress response and immune function in patients with tumors. Methods: Sixty patients who underwent selective radical gastrectomy for cancer were randomly divided into 3 groups: remifentanil group (group R), dexmedetomidine group (group D), and sufentanil group (group S). Remifentanil, dexmedetomidine, and sufentanil were used as general anesthetics. Endotracheal intubation and mechanical ventilation were performed after the spontaneous respiration disappeared. Then, the data were recorded, and blood samples were collected at all time points. Results: The heart rate significantly increased ( P < 0.05) at T1 in group S, and both heart rate and mean arterial pressure significantly increased ( P < 0.05) in group R when compared to group D. The heart rate significantly increased ( P < 0.05) at T2 in group S and group R. Furthermore, the heart rate significantly increased ( P < 0.05) at T3 and T4 in group S and group R. Intra-group comparison: The heart rate at T1–T4 and mean arterial pressure at T1–T4 significantly increased ( P < 0.05) in group S, and the heart rate at T1 and T4, and mean arterial pressure at T2–T4 significantly increased ( P < 0.05) in group R when compared to T0. The serum IL-6, IFN-γ, and β-EP significantly increased ( P < 0.05) at T0’ in group S and group R when compared to group D. Blood glucose, and serum IL-10, IFN-γ, and β-EP significantly increased ( P < 0.05), while IL-18 significantly decreased ( P < 0.05) at T1’ in group S and group R. Conclusion: Continuous infusion of dexmedetomidine in combination with the inhalation of sevoflurane is superior to sevoflurane + remifentanil or sufentanil in patients undergoing tumor surgery.

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Preclinical Pharmacology in the Rhesus Monkey of CW 1759-50, a New Ultra-short Acting Nondepolarizing Neuromuscular Blocking Agent, Degraded and Antagonized by L-Cysteine

Anesthesiology ◽

10.1097/aln.0000000000002408 ◽

2018 ◽

Vol 129 (5) ◽

pp. 970-988 ◽

Cited By ~ 2

Author(s):

John J. Savarese ◽

Hiroshi Sunaga ◽

Jeff D. McGilvra ◽

Matthew R. Belmont ◽

Matthew T. Murrell ◽

...

Keyword(s):

Heart Rate ◽

Mean Arterial Pressure ◽

Arterial Pressure ◽

Neuromuscular Blockade ◽

Blocking Agent ◽

Neuromuscular Blocking ◽

Neuromuscular Blocking Agent ◽

Duration Of Action ◽

Short Acting ◽

Circulatory Effects

Abstract Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New Background Structure–activity studies were performed to identify a new neuromuscular blocking agent retaining the ultra-short acting characteristics of gantacurium, including degradation and reversal by l-cysteine, but lacking its histaminoid properties in man. CW 1759-50 has emerged from this program. Methods Adduction of CW 1759-50 with l-cysteine was studied by high-performance liquid chromatography and mass spectrometry. Institutional Animal Care and Use Committee–approved comparisons of CW 1759-50 to gantacurium were performed in rhesus monkeys. ED95 for neuromuscular blockade was established. Spontaneous recovery was compared to reversal by l-cysteine in paired studies of boluses or infusions. In addition, changes in mean arterial pressure and heart rate after very large doses of 15 to 60 × ED95 were compared. Results The half-time of adduction of l-cysteine to CW 1759-50 in vitro was 2.3 min. The ED95 of CW 1759-50 was 0.069 ± 0.02 mg/kg; ED95 of gantacurium was 0.081 ± 0.05 mg/kg (P = 0.006). Duration of action (recovery to 95% twitch height after 98 to 99% blockade) was as follows: CW 1759-50, 8.2 ± 1.5 min; and gantacurium, 7.4 ± 1.9 min; (n = 8 and 9, P = 0.355). Administration of l-cysteine (30 mg/kg) shortened recovery (i.e., induced reversal) from CW 1759-50 after boluses or infusions (P always less than 0.0001). Recovery intervals (5 to 95% twitch) ranged from 6.1 to 6.7 min (and did not differ significantly) after boluses of 0.10 to 0.50 mg/kg, as well as control infusions (P = 0.426 by analysis of variance). Dose ratios comparing changes of 30% in mean arterial pressure or heart rate to ED95 for neuromuscular blockade (ED 30% Δ [mean arterial pressure or heart rate]/ED95) were higher for CW 1759-50 than for gantacurium. Conclusions CW 1759-50, similar to gantacurium, is an ultra-short acting neuromuscular blocking agent, antagonized by l-cysteine, in the monkey. The circulatory effects, however, are much reduced in comparison with gantacurium, suggesting a trial in humans.

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Additive Interactions between Propofol and Ketamine When Used for Anesthesia Induction in Female Patients

Anesthesiology ◽

10.1097/00000542-199503000-00005 ◽

1995 ◽

Vol 82 (3) ◽

pp. 641-648 ◽

Cited By ~ 83

Author(s):

T. W. Hui ◽

T. G. Short ◽

W. Hong ◽

T. Suen ◽

T. Gin ◽

...

Keyword(s):

Heart Rate ◽

Arterial Pressure ◽

Additional Term ◽

Anesthesia Induction ◽

Response Curves ◽

Intravenous Anesthesia ◽

Verbal Command ◽

Female Patients ◽

Loss Of Response ◽

Significant Difference

Background Propofol and ketamine may be paired for anesthesia induction and for total intravenous anesthesia. The nature of any sedative interactions occurring between propofol and ketamine are unknown. The combination when used for anesthesia induction in female patients was studied. Methods Quantal dose-response curves were determined in 180 female patients to whom the drugs were administered individually and in combination. Two minutes after administering the drugs, two endpoints were assessed. First, loss of response to verbal command (hypnosis) and then, in those who failed to respond to this endpoint, loss of response to a 5-s transcutaneous tetanus (anesthesia). Interactions were analyzed by fitting the data to a mathematical model in which response was analyzed in terms of the doses of the two drugs and an additional term included to describe nonadditive interactions. The incidences of apnea, arterial pressure, and heart rate changes during the first 5 min were recorded. Results At the hypnotic endpoint, the ED50s were 1.10 mg/kg propofol (95% CIs 0.93-1.27), 0.39 mg/kg ketamine (95% CIs 0.27-0.46), and the combination of 0.63 mg/kg propofol and 0.21 mg/kg ketamine (95% CIs 0.53/0.18-0.73/0.24). At the anesthetic endpoint, the ED50s were 1.85 mg/kg propofol (95% CIs 1.58-2.36) 0.66 mg/kg ketamine (95% CIs 0.58-0.77), and the combination of 1.05 mg/kg propofol and 0.35 mg/kg ketamine (95% CIs 0.88/0.29-1.27/0.42). The effects were additive at both endpoints; there was no evidence of an interaction. The ED50s for apnea were 1.61 mg/kg propofol (95% CIs 1.39-1.94), greater than 0.85 mg/kg ketamine and for the combination 1.50 mg/kg propofol and 0.50 mg/kg ketamine (95% CIs 1.15/0.38-3.09/1.03). The addition of ketamine did not significantly alter the ED50 for apnea of propofol. There was a significant difference in the arterial pressures among the three groups (P < 0.001). Using the combination, the cardiostimulant effects of ketamine balanced the cardiodepressant effects of propofol. There was no change in arterial pressure or heart rate after the noxious stimulus. Conclusions When using the combination, doses were additive at hypnotic and anesthetic endpoints. Ketamine had no influence on the incidence of apnea after propofol, and the net hemodynamic effects were minimal.

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