PubMed · 14225949
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C P ARTZ. 1964. RECENT DEVELOPMENTS IN BURNS.. https://doi.org/10.1016/0002-9610(64)90107-2
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Motor evoked potentials (MEPs) have shown promise as a valuable tool for monitoring intraoperative motor tract function and reducing postoperative plegia. MEP monitoring has been reported to contribute to deficit prevention during resection of tumors adjacent to motor structures in the cerebral cortex and spine, and in detecting spinal ischemia during thoracic aortic reconstruction. Many commonly used anesthetic agents have long been known to depress MEP responses and reduce MEP specificity for motor injury detection. Although new stimulation techniques have broadened the spectrum of anesthetics that can be used during MEP monitoring, certain agents continue to have dose-dependent effects on MEP reliability. Understanding the effects of anesthetic agents and physiologic alterations on MEPs is imperative to increasing the acceptance and application of this technique in the prevention of intraoperative motor tract injury. This review is intended as an overview of the effects of anesthetics and physiology on the reproducibility of intraoperative myogenic MEP responses, rather than an analysis of the sensitivity and specificity of this monitoring method in the prevention of motor injury.
The hydrogen-bond-acceptor properties of the carbonyl moiety in the 17beta-acetyl group on the D-ring of the anesthetic steroids (3alpha,5alpha)- and (3alpha,5beta)-3-hydroxypregan-20-one form an important part of the anesthetic steroid pharmacophore. 13,24-Cyclo-18,21-dinorcholanes containing a ketone or conjugated ketone group at C-20, C-22, C-23, or C-24 were prepared as conformationally constrained analogues of these anesthetic steroids and were used to probe for alternate locations for the D-ring hydrogen-bond-accepting carbonyl group. The analogues were evaluated (1). in [(35)S]-tert-butylbicyclophosphorothionate binding experiments, (2). in electrophysiological experiments using rat alpha(1)beta(2)gamma(2L) GABA(A) receptors expressed in Xenopus laevis oocytes, and (3). as tadpole anesthetics. In the binding assay, the relative order of potencies for the analogues in the 5alpha- and 5beta-series is identical. For the ketones, the order is 24-one >or= 23-one > 20-one > 22-one. Likewise, for the enones, the order is delta(22)-24-one > delta(20(22))-23-one > delta(22)-20-one > delta(23)-22-one. Similar relative orders of potencies are also found in the other two bioassays. The activities of the 24-one and delta(22)-24-one compounds were expected to be very low, because the carbonyl group in these compounds is located over the steroid C-ring and oriented toward C-8. Instead, these compounds have the highest activities in their respective series, with the delta(22)-24-one compounds having activities comparable to those of the reference anesthetic steroids. The electrophysiology results obtained with the 24-oxo-cyclosteroids suggest that rat alpha(1)beta(2)gamma(2L) GABA(A) receptors contain more than one donor for the hydrogen-bond-acceptor group of anesthetic steroids. The family of cyclosteroids should be useful for future structure-activity relationship studies of steroid modulation of other GABA(A) receptor subtypes.