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The mechanism of action of local anesthetics on synaptic transmission and their effects on synaptic components and on electrophysiologic properties of the nerve cell body are not clear. Therefore, the effects of lidocaine and bupivacaine on pre- and postsynaptic mechanisms underlying synaptic transmission in sympathetic ganglia were studied utilizing the techniques of intracellular recording and stimulation on isolated superfused superior cervical ganglia of rats. Lidocaine and bupivacaine either depressed or completely blocked synaptic transmission in sympathetic ganglia in a dose-dependent manner. Blockade of axonal conduction in presynaptic fibers was preceded by increased latency (the latency increased from 11.2 +/- 0.9 to 16.5 +/- 1.4 ms, mean +/- SEM, P less than 0.01) when the drugs were applied to the presynaptic nerves. Application of the drugs directly to the ganglion produced alterations in postsynaptic membrane properties consisting of decreased membrane resistance (from 40 +/- 3 to 32 +/- 3 M omega, P less than 0.01), increased firing threshold (from 14 +/- 0.5 to 18 +/- 0.5 mV, P less than 0.01), and decreased action potential amplitude (P less than 0.01) and/or blockade of action potential generation. Resting postsynaptic membrane potential did not change significantly. These changes were reversible. However, even after the excitatory postsynaptic potential resulting from presynaptic nerve stimulation had fully recovered during washout of the local anesthetic, the threshold for evoking the spike potential (firing level) still remained elevated for both presynaptic and intracellular stimulation of the ganglion cell, suggesting prolonged cell depression.(ABSTRACT TRUNCATED AT 250 WORDS)

While the effects of local anaesthetics on axonal conduction and axonal membrane have been extensively studied, there is little information about the actions of these agents on nerve cell soma. Therefore, the effects of the amide local anaesthetic bupivacaine on the electrophysiologic properties of the nerve cell soma were studied on isolated superfused superior cervical ganglia of rats. Administration of 100-200 nM of bupivacaine to the preparation produced marked changes in membrane properties of the cell soma. The resting membrane potential did not change, but the membrane resistance decreased 20% (P less than 0.01). The firing threshold, the action potential duration at 50% of maximal amplitude, and the intracellular current threshold for firing the cells increased significantly (P less than 0.01), while the action potential amplitude decreased significantly (P less than 0.01), before its complete blockade. The results show that the cell soma is a major site of action of local anaesthetics. The implication of the results is that when local anaesthetics are applied to areas where cell bodies and processes (axons and dendrites) are present together, such as during celiac plexus block, lumbar sympathetic block, stellate ganglion block, etc., they will all be effectively depressed and/or blocked.

The effects of intravenous administration of fentanyl (50 and 100 micrograms/kg) on the discharge activity of the medullary inspiratory neurons and of the phrenic nerve were studied following vagotomy in nine decerebrate, paralyzed mechanically ventilated cats. In six cats, the inspiratory neurons explored were in the dorsal respiratory group (DRG) associated with the nucleus of the tractus solitarius (NTS), while in the remaining three, they were in the ventral respiratory group (VRG). In the former group, the rhythmic discharge of the inspiratory neurons was disrupted by fentanyl and replaced by a continuous discharge superimposed with irregularly occurring bursts. These changes were also reflected by the phrenic nerve discharge. Inspiratory neuronal activity increased significantly (P less than 0.05) at 1 and 5 min after completion of fentanyl injection. Disruption of the rhythmic activity of the inspiratory neurons and its replacement by a continuous and irregular discharge may lead to sustained contraction of inspiratory muscles and cessation of respiration. In the VRG, the activity of the inspiratory neurons was totally abolished by fentanyl. Thus, it appears that different groups of medullary inspiratory neurons have differential sensitivity to fentanyl. Nalbuphine, an opiate agonist-antagonist, restored the normal pattern and magnitude of the activity of the inspiratory neurons.

The purpose of the present investigation was to determine the normal perioperative variations in the serum concentration of creatine phosphokinase (CPK) and its isoenzymes MM, MB, and BB, and of lactic dehydrogenase (LDH) and its isoenzymes LDH1 to LDH5 to distinguish operation-induced changes in these enzymes from those due to acute myocardial infarction or malignant hyperthermia. In 30 patients, 52 to 75 years of age undergoing elective orthopedic operations, 10 serial blood samples were obtained in the perioperative period: two samples before skin incision and eight samples after the incision over a time span of 70 hours. The preinduction mean serum CPK level of 141 U/L increased gradually and significantly and reached a maximum mean concentration of 809 U/L 34 hours after incision (p less than 0.01). The CPK-MM percent increased after incision, whereas that of CPK-MB and CPK-BB decreased, although their absolute values in terms of U/L rose. The preinduction mean serum LDH value of 173 U/L increased gradually after incision and achieved peak levels at 34 hours (203 U/L) and 58 hours (210 U/L) after incision (p less than 0.05). The LDH1:LDH2 ratio did not change. The LDH5 percent increased and peaked 10 hours after incision (p less than 0.05). There was a significant correlation between severity of operation-induced tissue damage and the serum CPK concentration (p less than 0.001). The large increase in total CPK (primarily MM fraction) occurring after surgery may minimize the percentile effects caused by an increase in MB level due to myocardial infarction.

The effects of intravenously administered fentanyl (25 micrograms/kg, n = 9; 50 micrograms/kg, n = 5) and alfentanil (12.5 micrograms/kg, n = 5; 25 micrograms/kg, n = 7) on the noxiously evoked, single-unit activity of cells in the nucleus reticularis gigantocellularis (NRGC) were studied in decerebrate cats. Only cells of the NRGC excited exclusively by supramaximal electrical stimulation of A delta fibers (noxious stimulation) of the superficial radial nerve were studied. The noxiously evoked activity of all cells in the NRGC was suppressed by the administration of opioids (by 58 and 88% for fentanyl, 25 micrograms/kg and 50 micrograms/kg, respectively; by 35 and 78% for alfentanil 12.5 micrograms/kg and 25 micrograms/kg, respectively). Fentanyl and alfentanil effects were antagonized by the intravenous administration of naloxone. These results indicate that opioid suppression of noxiously evoked activity is seen in neurons located in the brainstem, and thus suppression of brainstem neurons may be important in the production of fentanyl and alfentanil analgesia.

Intracellular recording and dye injection were used to study the morphological and electrophysiological properties of rat pelvic ganglion cells. The dye-injected cells measured on the average 37 μm by 22.5 μm and had a mean number of 1.5 primary processes (axon and dendrites). The cells received unmyelinated preganglionic inputs from either the pelvic (parasympathetic) or the hypogastric (sympathetic) nerves, but no cells received inputs from both nerves. The number of synaptic inputs to each cell varied between 1 and 5 with a mean of 2. Each cell had at least one large amplitude suprathreshold EPSP which always initiated an action potential. These properties, namely, morphological simplicity, small number of inputs, security of synaptic transmission and lack of convergence between sympathetic and parasympathetic inputs, suggest that the capacity for synaptic modulation and integration in this ganglion is minimal. Such a structure should therefore relay preganglionic information to target organs with little or no alteration.