Yoichi Maruyama

Anesthetics and Excitatory/Inhibitory Responses of Midbrain Reticular Neurons

The effects of nitrous oxide, halothane, ether, isoflurane, thiopental, and thiamylal on the excitatory as well as inhibitory responses of single neurons in the midbrain reticular formation (MRF), believed to be one of the most important sites for the regulation of wakefulness, were studied by long-term, extracellular microelectrode recording in cats and rats. All anesthetics except nitrous oxide suppressed the excitatory responses of MRF neurons evoked by somatosensory stimulation. The inhibitory responses markedly were potentiated by both barbiturates but variously affected by other inhalation anesthetics. Blockade of the inhibitory responses (disinhibition) was observed more frequently with the inhalation agents during the light state of anesthesia. Thus, suppression of excitatory responses is likely to be a general feature of the anesthetic state in terms of the behavior of MRF neurons. Further, potentiation of the inhibitory responses might be characteristic of harbiturate anesthesia.

Effects of Isoflurane on Spinal Inhibitory Potentials

The effects of isoflurane on segmental spinal cord potentials and heterosegmental slow positive potentials in response to fore- and hindpaw stimulation were studied in the rat. The heterosegmental slow positive potential and late (second) component of the slow positive wave (P2) of segmental spinal cord potential, thought to be primary afferent depolarization, an agent of presynaptic inhibition activated by a feedback loop via supraspinal structures, were greatly suppressed by the anesthetic. In contrast the negative wave (N1) of segmental spinal cord potential, believed to be synchronized activity of dorsal horn neurons, was only minimally affected. No differential effects of isoflurane on spinal cord potentials activated by fore- and hindpaws were found. Thus, the inhibitory activities of the spinal cord, particularly those produced by a feedback loop via supraspinal structures, are suggested to be highly vulnerable to isoflurane.

Dorsal Column Stimulation in Man: Facilitation of Primary Afferent Depolarization

The effects of cervical epidural dorsal column stimulation on the negative and slow positive waves of the spinal cord potentials recorded from the posterior epidural space at the lumbar enlargement, in response to intense stimulation of the tibial nerve in five neurologically normal subjects during neuroleptanesthesia were studied. Single pulses applied to the cervical dorsal cord near the midline produced slow positive potentials preceded by negative waves in the dorsal spinal cord at the level of the lumbar enlargement. The negative wave, believed to represent synchronized activities of interneurons, was inhibited up to 100 to 120 msec by conditioning dorsal column stimulation. The slow positive wave, thought to represent primary afferent depolarization, was facilitated for more than 100 msec with a transient inhibition for 10 to 40 msec. The results suggest that the pain-alleviating effect of dorsal column stimulation in man may be at least partly due to orthodromic and/or antidromic activation of descending inhibitory pathways which inhibit the responsible cells and facilitate primary afferent depolarization.

Effects of diazepam on evoked electrospinogram and evoked electromyogram in man.

&NA; The effects of intravenous diazepam (0.2 mg/kg) on the evoked electrospinogram recorded with an epidural electrode in the posterior epidural space of the lumbar enlargement and on the evoked electromyogram recorded with disc electrodes on the gastrocnemius muscle were studied following posterior tibial nerve stimulation in 14 subjects. Following administration of diazepam, the amplitude of P1, a reflection of afferent input through the dorsal root, was significantly depressed 3 minutes after administration of diazepam. The amplitude of P2 of electrospinogram, a reflection of primary afferent depolarization in the spinal cord was significantly increased 10 to 30 minutes after injection. The amplitude of the H‐reflex of the evoked electromyogram decreased significantly 3 to 30 minutes after injection, whereas that of the M‐wave remained unchanged. These results suggest that diazepam in the clinical doses may directly affect function of the human spinal cord.

Interaction between human evoked electrospinograms elicited by segmental and descending volleys.

Interaction between the slow negative-positive waves of human evoked electrospinograms produced by descending and segmental volleys was tested under general anaesthesia. A partial occlusion was demonstrated in these slow waves.

Brain and Spinal Cord Monitoring by Multispatial and Multimodal Evoked Potentials during Aortic Surgery

The most serious complications of aortic surgery are ischemic spinal cord and/or brain dysfunctions caused by an aortic clamp or emboli (15). As neurological signs and symptoms of ischemic lesions by aortic clamping are masked during anesthesia, an alternative measure should be undertaken for monitoring the brain and spinal cord functions. Although several neurophysiological techniques have been successfully used to detect early signs of CNS dysfunction due to carotid surgery (10, 17, 31, 34), there are some difficulties in monitoring CNS functions in aortic surgery. First, it is hard to define the anticipated sites of ischemia preoperatively, since there are considerable anatomical variations of arterial outflows to the spinal cord (7). Second, although the skin surface recording of spinal cord potential (SCP) has been attempted (32), it is often hard to reproduce the potential and also takes a considerable amount of time to average the response.

Spinal Cord Potentials Evoked by Ascending Volleys

When the dorsal surface of the human spinal cord is stimulated through a pair of electrodes situated in the cervical posterior epidural space (PES), a series of potentials can be recorded from the PES of the lumbosacral enlargement. The potentials begin with mono- or polyphasic spikes associated with the arrival of the volleys at the lumbar enlargement. Following these spikes, a series of slow potentials occur. These include a slow and sharp negative wave followed by a slow positive wave (Fig. 3.1). These slow negative (descending N) and positive (descending P) complexes resemble the segmentally evoked N1 and P2 waves (segmental N1 and P2), respectively. The similarity between the negative-positive complex evoked by descending volleys and the N1–P2 wave complex elicited by segmental nerve stimulation suggests that the origins of these slow descending N and P waves of SCPs are similar to those of the N1 and P2 waves of segmentally evoked SCPs (Shimizu et al., 1979a) (Table 3.1). The segmental N1 and P2 waves in humans show approximately the same characteristics as the slow negative and positive waves of the cord dorsum potential in animals (Shimoji et al., 1975, 1977), which are believed to be produced by the excitation of interneurons and primary afferent depolarization (PAD), respectively (Bernhard and Widen, 1953; Schmidt, 1971).

DESCENDING INHIBITION IN HUMAN SPINAL CORD

The effects of dorsal column stimulation (DCS) from the posterior epidural space (PES) on the negative (N1) and positive (P2) waves of human spinal cord potentials (SCPs), recorded from the PES in the lumbar enlargement, in response to an intense stimulation of the tibial nerve were studied in neurologically normal subjects. The cervical DCS itself produced the spikes and slow negative-positive complexes in the lumbar enlargement. The N1 wave, believed to be activities of interneurons, was inhibited up to 100–130 msec by the conditioning DCS. The P2 wave, thought to reflect primary afferent depolarization (PAD), was facilitated up to more than 100 msec preceded by a transient inhibition. Morphine (1 mg/kg, i.v.) suppressed both the N1 and P2 waves, while thiamylal sodium (5 mg/kg, i.v.) augmented both waves. The results suggest that the pain-alleviating mechanism of DCS in man may be at least partly due to the direct activation of descending inhibitory systems, which is distinct from that of morphine or thiamylal sodium.