OBJECTIVETo investigate the effect of high glucose on mitochondrial respiratory chain function in INS-1 cells.

METHODSThe pancreatic beta cell line INS-1 was divided into the normal control (NC), high glucose (HG), and N-acetyl-L-cysteine (NAC) pretreatment groups, which were cultured for 72 h in the presence of 5.5 mmol/L glucose, 16.7 mmol/L glucose, and 16.7 mmol/L glucose with 1.0 mmol/L NAC, respectively. The activities of the enzyme complexes I and III of the respiratory chain in the cells were assessed with spectrophotometry, the ATP levels were examined using a luciferinluciferase kit, and insulin levels detected by radioimmunoassay.

RESULTSThe activities of the respiratory chain enzyme complexes I and III were 1.53-/+0.24 and 1.08-/+0.22 micromol.mg(-1).min(-1) in high glucose group, respectively, significantly lower than those in the normal control group (2.31-/+0.33 and 1.92-/+0.39 micromol.mg(-1).min(-1), P<0.01). ATP and insulin levels also decreased significantly in high glucose group as compared with those in the normal control group (P<0.01). The addition of NAC partially inhibited high glucose-induced decreases in the enzyme complex activities, ATP levels and insulin secretion (P<0.05).

CONCLUSIONThe respiratory chain function is positively correlated to insulin secretion in INS-1 cells, and exposure to high glucose causes impairment of the two enzyme complexes activities through oxidative stress, resulting in the mitochondrial respiratory chain dysfunction. High glucose-induced damages of the mitochondrial respiratory chain function can be partially inhibited by NAC.

Cell Respiration ; drug effects ; Cells, Cultured ; Glucose ; pharmacology ; Humans ; Insulin-Secreting Cells ; cytology ; physiology ; Mitochondria ; physiology ; Oxidative Stress ; drug effects

OBJECTIVETo study the effects of pentobarbital sodium in generation and modulation of rhythmical respiration in neonatal rats.

METHODSThe effects of pentobarbital sodium were examined on hypoglossal nerve (XII) rootlets and inspiratory neurons in the medullary preparations including the medial region of the nucleus retrofacialis, pre-Bötzinger complex and the dorsal respiratory group of neonatal rats aged 0-3 days. The electrical activity of XII nerve rootlets and inspiratory neurons were recorded. Different doses of pentobarbital sodium (20, 40, 60, 80 micromol/L) were added into modified Krebs solution to observe changes in the discharge activity of XII nerve and inspiratory neurons. Bicuculline was used to further investigate the mechanisms that pentobarbital sodium suppresses respiration.

RESULTSThe discharge activity inhibition of XII nerve was increased as pentobarbital sodium doses increased from 20 to 60 micromol/L, but no significant difference was observed between the doses of 60 and 80 micromol/L. Bicuculline can partly restore the rhythmical respiration discharge activity.

CONCLUSIONPentobarbital sodium can suppress respiration partly via GABAA receptors.

Adjuvants, Anesthesia ; pharmacology ; Animals ; Animals, Newborn ; Dose-Response Relationship, Drug ; Medulla Oblongata ; cytology ; drug effects ; physiology ; Neurons ; drug effects ; physiology ; Pentobarbital ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Receptors, GABA-A ; physiology ; Respiration ; drug effects ; Respiratory Center ; drug effects ; physiology

Animals ; Blood Pressure ; drug effects ; Electric Stimulation ; Female ; Habenula ; physiology ; Lidocaine ; pharmacology ; Male ; Raphe Nuclei ; physiology ; Rats ; Rats, Wistar ; Respiration ; drug effects ; Serotonin ; physiology

OBJECTIVETo determine the role of glycine (Gly) in the generation and modulation of basic respiratory rhythm.

METHODSNeonatal (0-3 days) SD rats of either sex were used in this study. The medulla oblongata brain slice containing the medial region of the nucleus retrofacialis (mNRF) and the hypoglossal nerve rootlets was prepared, and the surgical procedure was performed in the modified Kreb's solution (MKS) with continuous carbogen (95% O(2) and 5% CO(2)) within 3 min. The rhythmical respiratory discharge activity (RRDA) of the hypoglossal nerve rootlets was recorded using suction electrode. Eighteen medulla oblongata slice preparations were divided into 3 groups and treated for 20 min with Gly receptor specific agonist Gly (10 micromol/L), Gly receptor antagonist strychnine (STR, 1 micromol/L), or Gly+STR after a 20 min Gly application. The changes in RRDA of the hypoglossal nerve rootlets were observed.

RESULTSGly significantly decreased the inspiratory time and integral amplitude (IA), but the changes of respiratory cycle (RC) and expiratory time (TE) were not statistically significant. STR induced a decrease in expiratory time and respiratory cycle without significantly affecting the inspiratory time or integral amplitud. The effect of Gly on the respiratory rhythm was partially reversed by additional application of STR.

CONCLUSIONGly may play an important role in the modulation of RRDA in the medulla oblongata slice of neonatal rats.

Animals ; Animals, Newborn ; Female ; Glycine ; pharmacology ; Hypoglossal Nerve ; physiology ; Male ; Medulla Oblongata ; physiology ; Rats ; Rats, Sprague-Dawley ; Respiration ; drug effects ; Respiratory Center ; physiology

OBJECTIVETo investigate the effects of iron supplement on function of mitochondrial respiratory of liver during exercise-induced hypochromic rats.

METHODForty healthy male Wistar rats were randomized into 5 groups (n = 8): static control (C), exercise-training (T), training with supplementation of small dose iron (S + T), training with supplementation of middle dose iron (M + T) and training with supplementation of large dose iron (L + T). Training performed incremental exercise for 8 weeks, 6 days/week, iron supplementation from the fifth week. Liver were prepared immediately after exhaustive running. Liver mitochondria were extracted by differential centrifugation. Spectrophotometric analysis was used to evaluate activities of electron transport chain complex (C) I-IV in liver mitochondria.

RESULTS(1) C I, CII and CIV activities in T group were increased significantly (P < 0.05, P < 0.01), CI - C IV activities in S + T, M + T and L + T groups were increased significantly (P < 0.05, P < 0.01) compared with those in C group. (2) CII activity in S + T group was increased remarkably (P < 0.05); CIII and CIV activities in M + T group were increased remarkably (P < 0.01); CI - CIV activities in L+ T group were increased remarkably (P < 0.05, P < 0.01) compared with those in T group.

CONCLUSIONLarge load exercise training composite iron supplementation can improve function of mitochondrial respiration of liver and the aerobic capacity. From the athletic ability , the middle dose iron supplementation is better during large load exercise training.

Anemia, Hypochromic ; metabolism ; physiopathology ; Animals ; Cell Respiration ; drug effects ; Hemoglobins ; metabolism ; Iron ; administration & dosage ; pharmacology ; Male ; Mitochondria, Liver ; drug effects ; physiology ; Physical Conditioning, Animal ; Rats ; Rats, Wistar

This study was performed to clarify the analgesic effect of ketamine injected into the first intercoccygeal (Co1-Co2) epidural space in standing cattle. Five adult cows were randomly received 3 treatments at least 1 week interval: 5, 10 and 20 mL of 5% ketamine. Sedation, analgesia, ataxia and other effects on cardiopulmonary and rumen functions were assessed before ketamine administration and until 120 min. The analgesia without sedation was shown at tail and perineum about 5 min after all three treatments. The duration of analgesia was significantly increased according to the volume of ketamine (p < 0.01). There was a similar tendency of ataxia with individual variation. There were minimal effects on cardiopulmonary and rumen functions. The present study showed that caudal epidural ketamine administration induced analgesia without sedation in cows, and the duration of analgesia was dose dependent with ataxia. However, the duration of analgesia after 5 and 10 mL ketamine administration is short for common surgical procedures and pain relief of perineum. Further studies are needed to prolong the duration of analgesia without side effects.
Analgesia, Epidural/*veterinary ; Analgesics/*administration & dosage ; Animals ; Blood Pressure/drug effects ; Body Temperature/drug effects ; Cattle/*physiology ; Female ; Heart Rate/drug effects ; Ketamine/*administration & dosage ; Respiration/drug effects ; Rumen/metabolism

The aim of the present study was to investigate the effect of endogenous carbon monoxide (CO) on respiratory rhythm. The experiments were carried out on the medullary slices of newborn Sprague-Dawley rats. The rhythmic discharge frequency (DF) of hypoglossal rootlets was taken as an index of rhythmic respiratory activity. The slices of medulla oblongata were superfused with ZnPP-9 (inhibitor of heme oxygenase), CO and hemin (substrate of heme oxygenase), respectively, to observe their effects on respiratory rhythm. The preparations were divided into 5 groups: control group of artificial cerebrospinal fluid (ACSF), group of ZnPP-9, group of exogenous CO, group of hemin and group of ZnPP-9 + hemin. The results obtained were as follows. In ZnPP-9 group, the rhythmic DF of the hypoglossal rootlets was increased (P<0.05); while in exogenous CO group, it was decreased (P<0.05). In the groups of hemin and ZnPP-9 + hemin, the rhythmic DF of the hypoglossal rootlets was increased (P<0.05). It is suggested that endogenous CO may play an important role in the regulation of respiratory rhythm.
Animals ; Animals, Newborn ; Carbon Monoxide ; physiology ; Female ; Hemin ; pharmacology ; Hypoglossal Nerve ; drug effects ; physiology ; Male ; Protoporphyrins ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Respiration

OBJECTIVETo investigate the role of dopamine-1 receptor in the modulation of basic respiration rhythm.

METHODSNewborn SD rat (0-3 days, n=20) brain stem slices containing the medial region of the nucleus retrofacialis (mNRF) were prepared with the hypoglossal nerve roots retained. The respiratory rhythmical discharge activity (RRDA) of the hypoglossal nerve was recorded using suction electrodes on these preparations, and the effects of dopamine-1 receptor on RRDA were investigated by application of the specific agonist of dopamine-1 receptor A68930 at different concentrations (0, 1, 2, and 5 micromol/L) in the perfusion solution.

RESULTSThe respiratory cycles (RC) and the expiratory time (TE) decreased progressively with gradual increment of the integrated amplitude (IA) after A68930 administration, and their changes were the most conspicuous at 5 min after the administration. A68930 at the concentrations of 2 and 5 micromol/L resulted in the most obvious changes in RC, TE, and IA (P<0.05), but IA exhibited no significant variation at 1 min after perfusion with 2 micromol/L A68930 (P>0.05). RC and TE were gradually shortened after treatment with increasing concentrations of A68930, which also caused gradual increment of IA, and at the concentration of 5 micromol/L, RC, TE, and IA all showed the most obvious changes (P<0.01).

CONCLUSIONSDopamine-1 receptor plays a role in the modulation of RRDA in isolated neonatal rat brainstem slice. A68930 may increase the frequency of respiration by shortening TE and enhance the respiratory activity by increasing the amplitude of inspiratory discharge of the respiratory neurons.

Animals ; Animals, Newborn ; Cell Separation ; Chromans ; pharmacology ; Dopamine Agonists ; pharmacology ; In Vitro Techniques ; Medulla Oblongata ; cytology ; physiology ; Neurons ; cytology ; Rats ; Rats, Sprague-Dawley ; Receptors, Dopamine ; physiology ; Respiration ; drug effects

OBJECTIVETo investigate the role of GABA A receptor in nikethamide-induced respiratory enhancement in the medullary slices of neonatal rats.

METHODSEx vivo medullary slices of neonatal rats (1 to 3 days old) containing the medial region of the nucleus retrofacialis with the hypoglossal nerve rootlets were prepared and perfused with modified Kreb's solution to record respiration-related rhythmic discharge activity (RRDA) from the hypoglossal nerve rootlets using suction electrodes. Thirty RRDA-positive slices were randomized into 5 equal groups and perfused with nikethamide (at concentrations of 0.5, 1, 3, 5, 7, and 10 microg/ml with the optimal nikethamide concentration determined), GABA (at 10, 20, 40, and 60 micromol/ to determine the optimal concentration), 10 micromol/ bicuculline, 10 micromol/ bicuculline plus 40 micromol/L GABA, and 5 microg/ml nikethamide followed by 5 microg/ml nikethamide plus 10 micromol/ bicuculline after wash out, respectively.

RESULTSNikethamide increased RRDA at the concentrations of 0.5-7 microg/ml, and 5 microg/ml nikethamide showed the most distinct effect on the inspiratory time (TI), integral amplitude (IA), and respiratory cycle (RC). GABA at 40 micromol/ showed the most effective inhibition of RRDA in terms of TI, IA, and RC. Bicuculline at 10 micromol/ could increase the IA, TI and RC, but the combination of 10 micromol/ bicuculline and 40 micromol/ GABA had no significant effects on RRDA. Compared with nikethamide used alone, nikethamide plus bicuculline significantly increased TI and IA without affecting RC.

CONCLUSIONNikethamide can enhance RRDA of the hypoglossal nerve rootlets in the medullary slices of neonatal rats, and the effect can be partially mediated by the GABA A receptor.

Animals ; Animals, Newborn ; Central Nervous System Stimulants ; pharmacology ; Female ; In Vitro Techniques ; Male ; Medulla Oblongata ; physiology ; Nikethamide ; pharmacology ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Receptors, GABA-A ; physiology ; Respiration ; drug effects ; Respiratory Center ; drug effects ; physiology

BACKGROUNDPropofol is increasingly used during partial support mechanical ventilation such as pressure support ventilation (PSV) in postoperative patients. However, breathing pattern, respiratory drive, and patient-ventilator synchrony are affected by the sedative used and the sedation depth. The present study aimed to evaluate the physiologic effects of varying depths of propofol sedation on respiratory drive and patient-ventilator synchrony during PSV in postoperative patients.

METHODSEight postoperative patients receiving PSV for <24 h were enrolled. Propofol was administered to achieve and maintain a Ramsay score of 4, and the inspiratory pressure support was titrated to obtain a tidal volume (VT) of 6-8 ml/kg. Then, the propofol dose was reduced to achieve and maintain a Ramsay score of 3 and then 2. At each Ramsay level, the patient underwent 30-min trials of PSV. We measured the electrical activity of the diaphragm, flow, airway pressure, neuro-ventilatory efficiency (NVE), and patient-ventilator synchrony.

RESULTSIncreasing the depth of sedation reduced the peak and mean electrical activity of the diaphragm, which suggested a decrease in respiratory drive, while VT remained unchanged. The NVE increased with an increase in the depth of sedation. Minute ventilation and inspiratory duty cycle decreased with an increase in the depth of sedation, but this only achieved statistical significance between Ramsay 2 and both Ramsay 4 and 3 (P < 0.05). The ineffective triggering index increased with increasing sedation depth (9.5 ± 4.0%, 6.7 ± 2.0%, and 4.2 ± 2.1% for Ramsay 4, 3, and 2, respectively) and achieved statistical significance between each pair of depth of sedation (P < 0.05). The depth of sedation did not affect gas exchange.

CONCLUSIONSPropofol inhibits respiratory drive and deteriorates patient-ventilator synchrony to the extent that varies with the depth of sedation. Propofol has less effect on breathing pattern and has no effect on VT and gas exchange in postoperative patients with PSV.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Blood Pressure ; drug effects ; physiology ; Female ; Hemodynamics ; drug effects ; physiology ; Humans ; Intensive Care Units ; Male ; Middle Aged ; Positive-Pressure Respiration ; methods ; Propofol ; therapeutic use ; Prospective Studies ; Respiration, Artificial ; methods ; Tidal Volume ; drug effects ; physiology ; Young Adult