Eye movements in systemically paralyzed macaque monkeys

Y&ion Res. Vol. 13. pp. 483-487. Pctgamon Press 1973. Printed in Great Britain,

RESEARCH EYE MOVEMENTS

NOTE

IN SYSTEMICALLY

PARALYZED

MACAQUE

MONKEYS PAULL. PEASE~ Department of PhysiologicalOptics, School of Optometry, University of California, Berkeley, California, U.S.A. (Received 2 August 1972) IN STIJDIES of the spatial organization of visual receptive fields it is essential either to eliminate eye movement or to be able to specify the position of the eyes relative to the stimuius.

Since receptive field centers of some cells in the monkey subtend less than 4’ of arc, stringent requirements are placed on the adequacy of eliminating unwanted eye movements. There is little doubt that satisfactory stability of the eyes can be achieved with animals anesthetized with a barbiturate and paralyzed with gallamine. Since techniques are available for recording from unanesthetized monkeys, it would be useful to examine the extent of eye movements in the absence of barbiturates. RODIECK,PET~IGREW,BISHOPand NIKARA (1967) presented results for residual eye movements in the paralyzed cat; however, there appears to be no similar report for the monkey. A small piece of a microscope cover slip was cemented to an opaque cornea1 contact lens that was placed on one eye of each of the three monkeys (Macaca fas~j~lar~s) used in this study. The lens was a single base curve lens, 9.1 mm in dia. and approximately O-6mm steeper than the central corneal curvature; it thus provided a very tight fit to the cornea. A low energy laser beam was reflected from the cover slip to a tangent screen placed 228 cm from the eye (1 cm on the tangent screen is approximately equal to a 0*125” rotation of the eye). The position of the eye was monitored at various times by marking the locus of the reflected beam on a piece of paper attached to the tangent screen or by recording the locus with a video tape. It is unlikely that the data reported here are contaminated by slippage of the contact lens on the eye. The same preparation that exhibited relatively large rapid movements under one drug condition showed only very small slow movements a few minutes later under a different drug condition. Furthermore, the eye movements encountered during receptive field studies were of the same order of magnitude as those reported here. Prior to the actual recording of data, each animal was anesthetized with sodium thiamylal (Surital; Parke-Davis, 17 mg/kg) in order to attach a head holding assembly to a skull implant, intubate the trachea, and to insert a Butterfly cannula (Abbott) into the external saphenous vein. No records of eye position (except when indicated otherwise) were recorded * Tbis investigation was supported in part by a Nationat Institutes of Health Research Fellowship, (2 F02 MH45700-03) from the National Institute of Mental Health and by a NationaI Eye Institute Grant (EY GQOl4)to R. L. DE VALOIS.Appreciative acknowledgement is given to R. L. DE VAUW for his advice. 1 Present address: The Massachusetts College of Optometry, 424 Beacon Street, Boston, Massachusetts 02115, U.S.A. 483

484

RESEARCHNOTE

until 2 hr after the anesthetic had been given, although the dosage used here is probably dissipated within the first hour. The results of the various conditions for each monkey are illustrated in Figs. 1,2, and 3. The successive position of the eye was recorded at 1 and 5 min intervals as indicated in the figures. The effect of the pulse and respiration are not shown but cause rhythmic movements 51’ of arc. Since d-tubocurarine and gallamine accumulate, a slight overestimate in the rate of continuous infusion of these paralytics will greatly prolong the recovery stage during a lengthy recording experiment; we therefore customarily use intermittent intravenous infusion. The same was done in this study, so the dosages in the figures refer to intravenous injections given every hour rather than by continuous infusion, although the latter might have led to a slightly smaller total excursion.

(b)

(a) Gallamine

Gallamine

H I min e-0 5 min

(c 1 Gallamine+Nitrous oxide

(d)

Gollamine

+ d-tubocurarine

7.5' FIG. 1. Eye position for a 3.5kg monkey under various conditions: (a) gallamine, 10 mg/kg/ hr; (b) gallamine. 6 mg/kg/hr; (c) gallamine, 6 mg/kg/hr + 70% N,O + 30% 02; (d) gallamine, 4 mg/kg/hr + d-tubocurarine, 1 mg/kg/hr. Marker refers to the angular rotation of the eye.

Gallamine (Flaxedil; Davis & Geck) alone, or in combination with nitrous oxide (70 %) and oxygen (30 %), is inadequate for stabilization of the eyes. Both saccades and slow drifts (ALPERN, 1962) are seen (see Figs. la, lb, lc, 2b and 3a) ; these generally do not exceed 0.25” in 1 hr though only 15 min records are shown here. Arousal stimuli (pinching or loud noises) will cause rapid excursions of approximately 0.25”. These movements start about 1-2 set after arousal and are in a predominately horizontal direction with a slow drift back to the position prior to arousal.

RESEARCHNOTE

485

In Fig. 2a is shown the effect of a barbiturate combined with gallamine. This animal was given an anesthetic dose of sodium pentobarbital (Nembutal; Abbott, 35 mg/kg) 3 hr prior to systemic paralysis with gallamine. The record starts 1 hr after systemic paralysis. It is quite likely that the effect of the barbiturate was waning, but nonetheless the total movement was less than 7’ of arc in a I-hr period. Unlike the gallamine records, this record showed only vertical movement and was without any rapid components.

(a) Gallamine + Nembutal

(b) Gallamine

0-o I min 045min

(c) Gallamine + d-tubocurarine

7.5’ FIG. 2. Eye position for a 2-Pkg monkey under various conditions: (a) gallamine, 7 mg/kg/hr + nembutal, 35 mg/kg given 3 hr prior to the gallamine; (b) gallamine, 7 mg/kg/hr; (c) gallamine, 4 mg/kg/hr + &ubocurarine. 1 mg/kg/hr.

The records labelled gallamine + d-tubocurarine (see Figs. Id, 2c and 3b) are 1 hr records and again are completely devoid of any rapid movements, i.e. saccades. In all cases the ratio of gallamine to d-tubocurarine (Tubocurarine Chloride Injection; Abbott) was 4/l and the amount of gallamine was 4 mg/kg/hr. Occasionally there were relatively large (7’) slow drifts but in general the eye did not move more than about 4’ of arc in a I-hr period. Arousal stimuli had no effect on the eye movement. The combination of gallamine and d-tubocurarine effects the best stability of the eyes for all conditions reported here except, in some cases, the barbiturate/gallamine record. Furthermore, a mixture of gallamine and d-tubocurarine reduce the risk of hypotension that occurs when d-tubocurarine is used alone and of tachycardia that results from gallamine. A careful dose-response study was not done, though some observations indicate that the gallamine/&tubocurarine ratio may be increased up to 7/l without increasing the eye movements from those seen with a 4/l ratio. A change in the mixture might be dictated in order to keep the heart rate constant. d-Tubocurarine differs from gallamine by having an action at adrenergic sites. It is not clear whether the stability achieved with the gallamine/d-tubocurarine mixture is due to the

486

RESEARCHNOTE (bf

0-4

Gal~amine~ d-tubocurarine

I min

0-05min

(c 1 Gallamine + Succinylchoiina

FIG.3. Eye position for a 3Gkg monkey under various conditions: (a) galfamine, 7 mg/kg/hr; (b) g&amine, 4 rn~kg~~ I- d-tubocurarine, 1 mg/kg/hr; (c) gallamine, 7 rn~~~~ + su~inyIcholine, 20 mg~kg~.

adrenergic blockade of d-tubocurarine on smooth muscle in the orbit and/or a potentiation effect of one agent on the other in their actions on skeletal muscle. [See EAKINSand KATZ (1971) for a review of the pharmacology of the extraocular muscles.] Small dosages of a depolarizing neuromuscular blocking agent (succinylcholine, decamethonium) when combined with a competitive (non-depolarizing) agent (d-tubocurarine, gallamine) may cause a partial antagonism of the block achieved with the competitive agent (KOELLE,1965). This antagonism can be seen in Fig. 3c where succinylcholine (Anectine; Burroughs Wellcome & Co.) was combined with galfamine. The record starts 1 hr after the administration of succinylcholine and 3 hr after gallamine, The eye movements are larger than with gallamine alone though still predominately horizontal. Both fast and slow movements are observed. If succinylcholine had been used to achieve the paralysis and gallamine given as an adjunct, it is possible that the movements would have been less, because the usual depolarizing block characteristic of succinylcholine can change to a nondepolarizing block if succinylcholine is given over a long period of time. Succinylcholine causes an elevation in the intra-ocular pressure (EAKINSand KATZ, 1971) and thus, if for no other reason, should be avoided in visual studies where normal function is the ultimate goal. The data reported by RODIECKet al. (1967) for the paralyzed cat anesthetized with nitrous oxide (70%) and oxygen (30 “/,) are similar to those reported here. However, in the gallamine records, the cat shows primarily vertical movement (up to 2”) whereas the monkey exhibits predominantly horizontal movement (up to 0.25’). This difference in direction of movement may be correlated to the number of fibers in the four recti muscles (PEACHEY,1971). In the cat the ratio of fibers in the inferior and superior recti to the medial and lateral recti is approximately 1*3/l, whereas the same ratio for the monkey is 0*74/l.

&SEARCH

NOTE

487

In both the cat and monkey, the greatest stability was achieved by use of a mixture of gallamine and d-tubocurarine, though a cervical sympathectomy may further reduce the movement in the cat (RODIECK er al., 1967). Since Rodieck et al. were not able to improve the stability by mechanical clamping of the eyes, the optimal condition in both cat and monkey for eliminating unwanted eye movement is achieved by a mixture of gallamine and dtubocurarine. REFERENCES ALPERN,M. (1962). Types of movement. In 2% Eye (edited by H. D~vso~), Vol. 3. Academic Press, New York. EAKINS,E. E. and KATZ, R. (1971). The pharmacoIogy of extraocular muscle. In The Control ofEye Mmmeats (edited by P. BACH-Y-RITA and C. C. COLLINS).Academic Press, New York. KOELLS, G. B. (l%S). Neuromuscular blocking agents. In Tire ~~~~g~~ &rsis uf ~r~ut~~~ (edited by L. S. GOOD~UNand A. GILLMAN),3rd edn., Macmillan,Toronto. PEACHEY, L. (1971). The structure of the extraocular musc!e fibers of mammals. In The C5mol uf Eye Movements(op. tit).

RODIIXK,

R. W., PEI-IIGREW,J. D., BISHOP,P. 0. and NIKARA,T. (1967). Residual eye movements in receptive-field studies of paralyzed cats. I&ionRes. 7, 107410.