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EFFECT OF LOCAL ANESTHETICS ON CELL DIVISION AND MIGRATION FOLLOWING THERMAL BURNS OF CORNEA FREE

GEORGE K. SMELSER, Ph.D.; V. OZANICS, M.S.
[+] Author Affiliations

Read at a meeting of the New York Academy of Medicine, Section of Ophthalmology, Nov. 20, 1944.

The work described in this paper was done under a contract, recommended by the Committee on Medical Research, between the Office of Scientific Research and Development and Columbia University.


Arch Ophthalmol. 1945;34(4):271-277. doi:10.1001/archopht.1945.00890190271001
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It has long been recognized that the frequent topical application of anesthetics delays the repair of epithelial injuries of the cornea. This observation has been made clinically (Stallard1), and more rigorously controlled comparisons have been made on laboratory animals on which treated and untreated standardized corneal abrasions have been inflicted (Gundersen and Liebman,2 Friedenwald and Buschke3). Such studies have lead to attempts to secure less harmful drugs which are yet effective anesthetics.

The search for an anesthetic agent which does not inhibit healing is obviously of practical value. It is of equal interest to determine whether inhibition of healing processes is proportional to the anesthetic properties and is, therefore, possibly due to the same factors which produce anesthesia. In such a case normal healing rate and anesthesia would be incompatible. It is the purpose of this paper to show that anesthesia and normal healing are compatible, to

REFERENCES

Stallard, H. B.:  Methods of Anesthesia and Analgesia for Ophthalmic Operations , in Ridley, F., and Sorsby, A.: Modern Trends in Ophthalmology , London, Butterworth & Co., Ltd., 1940;, chap. 49.
Gundersen, T., and Liebman, S. D.:  Effect of Local Anesthetics on Regeneration of Corneal Epithelium , Arch. Ophth. 31:29 ( (Jan.) ) 1944;.
Friedenwald, J. S., and Buschke, W.:  The Influence of Some Experimental Variables on the Epithelial Movements in the Healing of Corneal Wounds , J. Cell. & Comp. Physiol. 23:95, 1944;.
Arey, L. B.:  Wound Healing , Physiol. Rev. 16:327, 1936;.
Wigglesworth, V. B.:  Wound Healing in an Insect (Rhodnius Prolixus Hemiptera) , J. Exper. Biol. 14:364, 1937;.
Arey, L. B., and Covode, W. M.:  The Method of Repair in Epithelial Wounds of the Cornea , Anat. Rec. 86:75, 1943;.
Mann, I.:  Study of Epithelial Regeneration in Living Eye , Brit. J. Ophth. 28:26, 1944;.
Smelser, G. K., and Ozanics, V.:  Effect of Chemotherapeutic Agents on Cell Division and Healing of Corneal Burns and Abrasions in the Rat , Am. J. Ophth. 27:1063, 1944;.
Baba, H.:  Vergleichende Beobachtungen über die durch Instillationen von verschiedenen lokalen Anaesthetica hervorgerufenen Augenveränderungen , abstracted, Zentralbl. f. d. ges. Ophth. 40:555, 1938;.
The solutions of cocaine hydrochloride were obtained in the hospital pharmacy. The solutions of all other drugs were prepared in our laboratory. Some of the ointments were also prepared in our laboratory in the hydrous wool fat base mentioned; others were proprietary ointments, obtained as follows: Ophthalmic Ointment Butyn Sulfate 2% and Metaphen 1:3,000, Abbott Laboratories; Ophthalmic Ointment Butesin Picrate 1% and Butesin 1%, Abbott Laboratories; Pontocaine Base Eye Ointment (0.5 per cent tetracaine base), Winthrop Chemical Company, Inc.; Nupercainal (nupercaine base, 1 per cent), Ciba Pharmaceutical Products, Inc., and Holocaine Hydrochloride (2 per cent phenacaine hydrochloride), Abbott Laboratories. These products were purchased locally.
Friedenwald, J. S., and Buschke, W.:  The Effects of Excitement, of Epinephrine and of Sympathectomy on the Mitotic Activity of the Corneal Epithelium in Rats , Am. J. Physiol. 141:689, 1944;.
Friedenwald, J. S., and Buschke, W.:  Mitotic and Wound-Healing Activities of Corneal Epithelium , Arch. Ophth. 32:410 ( (Nov.) ) 1944;.
Since this article was submitted for publication, we have carried out similar experiments with metycaine hydrochloride (Lilly) solutions and ointments. The burned areas, treated with a 1 per cent solution of metycaine hydrochloride, were 134 per cent larger than the untreated control burns. This delay in healing was similar to that caused by a 0.1 per cent solution of nupercaine hydrochloride. There were 17 per cent fewer mitotic figures in these treated eyes, a depression similar to that caused by butacaine sulfate. The ointment containing 4 per cent metycaine hydrochloride delayed epithelization a little less than did the ointment containing 0.5 per cent tetracaine base. The burned area was 159 per cent greater than the average area of the control burns. The number of mitotic figures was 25 per cent less in the ointment-treated eyes, an effect similar to that obtained with the ointment containing butacaine sulfate, 2 per cent, and metaphen.
Michaelis, M., and Quastel, J. H.:  The Site of Action of Narcotics in Respiratory Processes , Biochem. J. 35:518, 1941;.
Herrmann, H.; Moses, S. G., and Friedenwald, J. S.:  Influence of Pontocaine Hydrochloride and Chlorobutanol on Respiration and Glycolysis of Cornea , Arch. Ophth. 28:652 ( (Oct.) ) 1942;.

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Stallard, H. B.:  Methods of Anesthesia and Analgesia for Ophthalmic Operations , in Ridley, F., and Sorsby, A.: Modern Trends in Ophthalmology , London, Butterworth & Co., Ltd., 1940;, chap. 49.
Gundersen, T., and Liebman, S. D.:  Effect of Local Anesthetics on Regeneration of Corneal Epithelium , Arch. Ophth. 31:29 ( (Jan.) ) 1944;.
Friedenwald, J. S., and Buschke, W.:  The Influence of Some Experimental Variables on the Epithelial Movements in the Healing of Corneal Wounds , J. Cell. & Comp. Physiol. 23:95, 1944;.
Arey, L. B.:  Wound Healing , Physiol. Rev. 16:327, 1936;.
Wigglesworth, V. B.:  Wound Healing in an Insect (Rhodnius Prolixus Hemiptera) , J. Exper. Biol. 14:364, 1937;.
Arey, L. B., and Covode, W. M.:  The Method of Repair in Epithelial Wounds of the Cornea , Anat. Rec. 86:75, 1943;.
Mann, I.:  Study of Epithelial Regeneration in Living Eye , Brit. J. Ophth. 28:26, 1944;.
Smelser, G. K., and Ozanics, V.:  Effect of Chemotherapeutic Agents on Cell Division and Healing of Corneal Burns and Abrasions in the Rat , Am. J. Ophth. 27:1063, 1944;.
Baba, H.:  Vergleichende Beobachtungen über die durch Instillationen von verschiedenen lokalen Anaesthetica hervorgerufenen Augenveränderungen , abstracted, Zentralbl. f. d. ges. Ophth. 40:555, 1938;.
The solutions of cocaine hydrochloride were obtained in the hospital pharmacy. The solutions of all other drugs were prepared in our laboratory. Some of the ointments were also prepared in our laboratory in the hydrous wool fat base mentioned; others were proprietary ointments, obtained as follows: Ophthalmic Ointment Butyn Sulfate 2% and Metaphen 1:3,000, Abbott Laboratories; Ophthalmic Ointment Butesin Picrate 1% and Butesin 1%, Abbott Laboratories; Pontocaine Base Eye Ointment (0.5 per cent tetracaine base), Winthrop Chemical Company, Inc.; Nupercainal (nupercaine base, 1 per cent), Ciba Pharmaceutical Products, Inc., and Holocaine Hydrochloride (2 per cent phenacaine hydrochloride), Abbott Laboratories. These products were purchased locally.
Friedenwald, J. S., and Buschke, W.:  The Effects of Excitement, of Epinephrine and of Sympathectomy on the Mitotic Activity of the Corneal Epithelium in Rats , Am. J. Physiol. 141:689, 1944;.
Friedenwald, J. S., and Buschke, W.:  Mitotic and Wound-Healing Activities of Corneal Epithelium , Arch. Ophth. 32:410 ( (Nov.) ) 1944;.
Since this article was submitted for publication, we have carried out similar experiments with metycaine hydrochloride (Lilly) solutions and ointments. The burned areas, treated with a 1 per cent solution of metycaine hydrochloride, were 134 per cent larger than the untreated control burns. This delay in healing was similar to that caused by a 0.1 per cent solution of nupercaine hydrochloride. There were 17 per cent fewer mitotic figures in these treated eyes, a depression similar to that caused by butacaine sulfate. The ointment containing 4 per cent metycaine hydrochloride delayed epithelization a little less than did the ointment containing 0.5 per cent tetracaine base. The burned area was 159 per cent greater than the average area of the control burns. The number of mitotic figures was 25 per cent less in the ointment-treated eyes, an effect similar to that obtained with the ointment containing butacaine sulfate, 2 per cent, and metaphen.
Michaelis, M., and Quastel, J. H.:  The Site of Action of Narcotics in Respiratory Processes , Biochem. J. 35:518, 1941;.
Herrmann, H.; Moses, S. G., and Friedenwald, J. S.:  Influence of Pontocaine Hydrochloride and Chlorobutanol on Respiration and Glycolysis of Cornea , Arch. Ophth. 28:652 ( (Oct.) ) 1942;.

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