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Phenyldiguanide and veratridine given i.v. in doses of 25–60 and 12–30 μg/kg, respectively, were found to produce depression preceded by brief acceleration of spontaneous γ efferent and attendant spindle afferent discharge in cats under chloralose-urethane anesthesia. This effect resembles that described earlier for nicotine. The depressant action of phenyldiguanide and veratridine, which occurred in both extensor and flexor γ fibers, was abolished by bilateral cervical vagotomy or spinal transection, suggesting that it was caused by a reflex action arising from sensory receptors in the cardiopulmonary region. The γ acceleratory effect, on the other hand, which was not entirely prevented by vagotomy, is likely to originate from more widely distributed sensory receptors including cutaneous endings. Excitation of cardiopulmonary receptors causes the autonomic effects of phenyldiguanide and veratridine (bradycardia, hypotension and apnea). The simultaneous onset of hypotension and γ depression, as well as other observations, indicate that the γ depression cannot be due to the fall in blood pressure and that, for a given drug, both effects may be due to excitation of the same sensory ending. Since receptors in different portions of the cardiopulmonary region have been implicated in the autonomic reflex effects of phenyldiguanide, veratridine and nicotine, the same would then hold true for the γ depressant action of these drugs. The γ depression elicited by phenyldiguanide was abolished by naphthylguanidine, sparing the effects of veratridine and nicotine; the γ depression elicited by nicotine was blocked by hexamethonium, sparing the effects of phenyldiguanide and veratridine. This selective antagonism suggests the existence of distinct pharmacological receptor sites situated on the sensory endings excited by the drugs, γ Acceleration, rather than depression, was the predominant effect of i.v. injection of 5-hydroxytryptamine. This effect also was probably due to stimulation of sensory endings, since it was abolished by blockade of the neuronal M receptors with morphine.

Based on the rationale that splanchnicectomy might interrupt a viscero-visceral autonomic reflex are responsible for bronchospasm and bronchorrhea, this operation has been performed on 24 infants and children with mucoviscidosis, most of whom were poor operative risks. Three of them died at or soon after operation, and six others have died at intervals of from 2 to 12 months postoperatively. Of the remaining 15, manifestations are essentially unchanged in five, and equivocally ameliorated in six. No information could be secured concerning the late effects in one child (Patient 17, K. W.). Three patients may have been materially benefited by the procedure.

A hypothesis is advanced that sudden unexpected death in infancy (S.U.D.) is a preventable condition that results from the magnesium-deprivation syndrome of growth (M.D.G.) which is most striking in young, rapidly growing infants and animals. This syndrome may develop during the rapid growth of a young infant fed magnesium-poor breast milk from a malnourished, multi-parous mother, or an artificial diet poor in magnesium in relation to calcium, phosphorus, and protein— nutrients that increase the metabolic requirement for magnesium. Premature and low-birth-weight infants with poor magnesium stores and rapid growth-rates are most vulnerable. It is suggested that the key to the pathogenesis of S.U.D. is the fact that magnesium deficiency leads to the liberation of histamine without exogenous histamine liberators, and initiates autonomic reflex activity through the vagus nerve; the result is histamine shock. Histamine shock approximates to anaphylactic shock and is characterised by bronchospasm, apnoea, emphysema, arteriolar dilatation, and increased permeability leading to pulmonary œdema which is often haemorrhagic, and circulatory collapse During shock, heparin is released from the liver, resulting in incoagulability of the blood. This seems to explain the anaphylactoid character of S.U.D. despite the failure to demonstrate allergens. It is postulated that liberation of acetylcholine secondary to hypo-magnesaemia leads to cholinergic symptoms and neuromuscular hyperirritability. Histamine liberation is greatest in the neonatal period and when the body temperature and blood-sugar are lowest; this might explain the highest incidence of S.U.D. in the first months of life in the early morning hours of winter.

Rheographic recording of circulatory variations on the forearm following caloric-vestibular stimulation in 33 tests on 25 subjects showed no significance in 10 subjects (30° water, fasting), while 5 persons (30° water, non-fasting) exhibited significance during the periods 60–70 sec and 80–90 sec after the start of the irrigation. In 10 persons (20°C water, non-fasting) there was significance 80–90 sec and 100–110 sec after the irrigation was started. In a control group of 8 out of the 25 subjects (37°C water, non-fasting) significance was found 100–110 sec after the irrigation was started.

Severance of the spinal cord at the tenth thoracic vertebra in cats, not anesthetized but under bulbocapnine, decreases the amplitude of the galvanic skin reflex from the forefeet, in response to an auditory stimulus just as it reduces the intensity of the ipsilateral flexion reflex of the forelegs.

Preliminary experimentation on ring doves to ascertain whether they might regulate any aspects of their reproductive behavior in terms of olfactory cues was vitiated by the discovery that their sectioned olfactory nerves had apparently regenerated. Concurrent work on frogs has shown that the olfactory receptors degenerate after axotomy and are replaced by new ones. This phenomenon was studied in pigeons. All transected nerves were found to be healed. Electrical recording from the regenerated nerves revealed apparently normal receptor function and, indirectly, autonomic reflex responsiveness. Previously untrained pigeons learned an olfactory discrimination after reconstitution of the peripheral olfactory system using a conditioned suppression procedure. The olfactory nerves of trained pigeons were sectioned and the behavioral response recovered within 16-82 days. The gross sizes of primary olfactory nerves and olfactory bulbs were frequently much less than those of controls, but on the ultrastructural level there was no recognizable morphological deficiency in the receptor cellular organelles or terminal synaptic contacts in bulbar glomeruli. Recent results by other workers indicate that pigeons utilize olfactory cues in homing performance.

Summary Using female dogs, changes in the urethral pressure profile in response to vesical distension were studied. It was noted that during the collecting phase there was an increase in the amplitude of the profile tracing. These experiments revealed that this increase is not mediated through an autonomic reflex and does not reflect a significant enhancement of a-adrenergic activity. These changes are mainly due to increased tension of the urethral muscle, secondly to detrusor stretch.

This study investigated the possibility that the hippocampus exerts a modulating influence on autonomic reflexes. Electrical stimulation of the dorsal and ventral hippocampus of unanaesthetized rabbits had no effect on an olfactory-trigeminal induced inhibition of respiration and heart rate. Neither was a conditioned fear induced acceleration of respiration and heart rate influenced by hippocampal stimulation. Even prolonged electrical seizure discharges in the hippocampus did not alter, or only slightly influenced, normal or the induced autonomic changes. Hippocampal stimulation did evoke weak autonomic changes as part of an arousal reaction to which however the animals became quickly habituated.

1. 1. When application of the term “sudden death” is limited to instances wherein death occurred more or less instantaneously and in some degree unexpectedly, the vast majority of its victims will be found to suffer from organic heart disease, predominantly coronary occlusive disease. 2. 2. In two major studies of patients dying suddenly of coronary disease, the incidence of coronary thrombosis approximated only 25 per cent, and of acute myocardial infarction, something less than 20 per cent. 3. 3. The presence of coronary occlusive disease does not, per se, explain why the afflicted individual should have died abruptly. Others with lesions similar in kind and more extensive in degree may live on indefinitely. 4. 4. Although cardiac standstill and ventricular fibrillation are the established immediate causes of most instances of sudden death, precise documentation of these events in clinical circumstances is lacking. 5. 5. Experimental studies of Harris, Moe and others indicate: (a) that general bodily anoxia and shock predispose to pacemaker arrest and A-V conduction disturbances; (b) that localized boundaries of injury developing in sequence to severe coronary insufficiency are the sites at which tachysystole and fibrillation develop—probably as a consequence of production at these boundaries of high action potentials during the ventricular excitation process; (c) that general hypoxia induced by lowering the content of oxygen in inspired air may diminish the gradient of concentration of oxygen at the boundary of injury and reduce the frequency of extrasystolic discharge; (d) that autonomic reflex activity may play a major role in increasing the vulnerability of the heart both to cardiac arrest and ventricular fibrillation. 6. 6. Sudden death apparently does occur, albeit infrequently, in individuals whose hearts are morphologically normal, thus recalling Dr. Soma Weiss' statement that “There is a close similarity and interrelation between the mechanism of instantaneous death and that of syncope; frequently, indeed, instantaneous death is merely fatal syncope. 7. 7. With obvious justification, an increased understanding of these reflex phenomena which exert protection in one individual and facilitate death in another may be zealously pursued.

Premedication is an old idea. Claude Bernard suggested using morphine before anesthesia to facilitate induction. Misconceptions are prevalent concerning premedication. Often it is ordered empirically without rational basis. This exhibit indicates accepted uses and common misconceptions. Why Give Premedication? Preanesthetic medication is necessary (1) for psychic sedation primarily, (2) to minimize secretions, (3) to fortify impotent anesthetics, and (4) as prophylaxis for suppression of vagal and other autonomic reflex activity. Summary Premedication is part of the anesthetic. The desired goal is tranquility and amnesia without loss of consciousness. The narcotics combined with belladonna alkaloids still remain the most reliable and versatile agents for premedication. What Are the Criteria for Selection of Premedication? Premedication is part of the anesthetic. Drugs and methods must be individualized for a particular patient and technique of anesthesia. The anesthetist is best qualified to prescribe it. It should be his prerogative to select it. What Drugs

IN EARLIER investigations 1 it was found that (1) reiterated elicitation of a single autonomic reflex or (2) hard work by which the subject was generally fatigued resulted in disintegration of central autonomic mechanisms of control. When the pupillary reflex to light was fatigued and finally exhausted by repeated stimuli, two related sequences of events occurred: In the periphery, a gradual, although rhythmically interrupted, disintegration of the reflex shape. Certain types of reflex shapes appeared and were described as shapes of slight disinhibition of contraction, the tonohaptic reflex, W- and V-shapes, sluggish and inextensive contraction, prolonged latency periods, and absence of the reflex. In the centers of autonomic control, corresponding processes of disintegration, the sequence of which was expressed in a general law: "All nervous fatigue is central in origin; the sympathetic centers fatigue prior to the parasympathetic centers, the cortical prior to the subcortical." All fatigue shapes which, transitorily and

Tactile classical conditioning of an autonomic reflex (pupillary dilation and constriction) and a somatic response (eyeblinking) was attempted in two separate experiments with one-month-old infants. The tactile CS was effective for conditioning eyeblinking but was ineffective for elaborating conditional pupillary reflex dilation or constriction. These differences were related to the interaction between stimulus and response in infant conditioning and the source of nervous system innervation of the CR as it relates to conditionability.

To the Editor.— Autonomic dysreflexia with its many variations form an integral and troublesome way of life for spinal cord injury patients. 1,2 The attending physician must acquaint himself with these vagaries, if he is to avoid labeling all of his patients' complaints as psychosomatic or psychoneurotic manifestations. Bors and Comarr 3 state that, physiologically, all vascular segmental reflex activity is integrated at supraspinal levels of normal man, preventing extreme fluctuations of blood pressure. This integration of vasomotion is lost in patients with lesions of the neuraxis above the splanchnic outflow, ie, above levels between T-4 and T-6. It has been stated that autonomic dysreflexia occurs with lesions of the cord at the T-4 level and above. Also clinically significant autonomic reflex may be seen in patients with myelopathy cephalad to the sixth thoracic dermatome. Autonomic dysreflexia also may occur in lesions below the sixth segment. It has been the

PATHOLOGIC autonomic reflex mechanisms which accompany injuries to the cervical and upper thoracic segments of the spinal cord have been observed and described and their clinical manifestations studied by means of physiologic investigations during the period following the first and second world wars. 1 Many pathophysiologic phenomena were explained; yet no therapeutic effort was reported to eliminate permanently the most dangerous of these, namely, paroxysmal hypertension, which is caused by distention of hollow viscera and which threatens the life of the patient. The present study was stimulated by a previous observation 2 on three cases in which pathologic autonomic reflexes became suppressed after the subarachnoid injection of absolute alcohol administered in order to abolish skeletal spasticity. 3 Since subarachnoid alcohol block interrupts both afferent and efferentpathways below the level of injection, posterior rhizotomy at segments which supply the highly reflexogenic areas of the genitalia, bladder, and rectum would be

HEAD AND RIDDOCH, 1 in their classic experiments on patients with gross spinal cord injuries, found facilitation of spinal reflexes in that part of the cord below the level of the lesion and without suprasegmental control. It was shown that a sufficient stimulus to any receptive surface whose afferent fibers entered the distal stump of the cord was liable to evoke a massive response which overflowed widely into regions of the spinal cord normally associated with other reflexes (assuming that recovery from spinal cord "shock" and resumption of reflex activity of the distal stump of the spinal cord was not prevented by such complications as general infection and toxemia). Especially investigated were abnormal autonomic reflex effects due to afferent impulses from bladder and bowel distention, both those of spontaneous occurrence due to urinary obstruction or flatulence and those artificially induced by inflation of the bladder or enemas. Outbursts of intense