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RESULTS
All rabbits attained surgical stage of anesthesia as assessed by response to ear pinching and pedal reflex. The mean basal heart rate immediately after ketamine anesthesia (275±9/min) did not vary significantly (P<0.01) after ocular manipulation (270±10/min). Use of either of the topical anesthetics proparacaine, lignocaine, bupivacaine before ocular manipulations in this group of animal, did not significantly change the heart rate (270±7,270±6,264±6/min) recorded with ocular manipulation under ketamine alone.
A significant reduction in heart rate was recorded after ocular manipulation (245±11/min, P<0.01) under propofol anesthesia as compared to the basal heart rate (278±8/min) recorded after propofol anesthesia. Use of topical anesthetics proparacaine, lignocaine, bupivacaine prior to ocular manipulation in this group of animal significantly (P<0.01) prevented the decreased heart rate recorded after ocular manipulation under propofol anesthesia alone (vs 270±5, 277±4, 276±6/min).
Uniform gradual reduction in the diameter of created corneal defect was observed after topical fluorescein dye test in all the groups (Figure 2 AH). Any intraocular changes i.e. uvietis, hypema, lens opacity or retinal changes were not observed in any animal during the period of study. Lack of anterior epithelial cells and uniform arrangement of collagen in the stromal layer was seen in sections of cornea subjected to superficial keratectomy (Figure 3AD). Histological sections stained either with hematoxilin eosin or sirius red did not reveal any difference in corneal healing and collagen deposition between the control and topical anesthetics group (Figure 4AD).
Ultrastructural study of the portion of the intact cornea treated with topical anesthetic showed no intracellular changes and was similar to section of the untreated cornea. The cellular junctions appeared normal. The nuclear membrane integrity was preserved and the chromatin appeared uniformly distributed. No dilatations of the endoplasmic reticulum and intact mitochondrial outer and inner membrane were observed.
DISCUSSION
Oculocardiac reflex (OCR) is mainly encountered during strabismus surgery, with incidence of OCR ranging from 32% to 90%. It is also observed during LASIK[1], eye muscle surgery, repair of detached retina, compression of gasserian ganglion, enucleation of eye, by contact lens[2], and repair of nasal fracture under general anesthesia. As the expression of OCR is influenced by the anesthetic regimen, we have investigated the incidence of oculocardiac reflex with ketamine and propofol anesthesia by a variety of ocular stimulus in rabbit. We have also used topical anesthetics for prevention of OCR. No preanesthetics i.e. atropine sulphate or other anesthetic combination were used to avoid any masking effect of preanesthetics on the incidence OCR with the two anesthetics under study.
Rabbit is a preferred model for assessment of new technologies as well as ophthalmic surgical procedures for its large size of the eye[14], docile nature and lower cost compared to dog or primate. Rabbit has been used as a model for studies on oculocardiac, oculorespiratory reflex. In the present study ocular manipulations under ketamine anesthesia did not produce any significant change in the heart rate. However, a significant reduction in heart rate was recorded after ocular manipulation under propofol anesthesia. Ten percent decrease in heart rate or occurrence of any arrhythmia induced by extraocular muscle manipulation is considered as OCR in the present study. In case of propofol anesthesia the basal heart rate was recorded 3 minutes after induction to eliminate the transient increase in heart rate[15] which occurs after propofol anesthesia and to make the basal heart rates of both anesthetics comparable. Similar studies report lower incidence of OCR with ketamine anesthesia in comparison to other anesthetic combinations [16]. Low incidence of OCR under ketamine anesthesia could be attributed to its profound analgesic property as we hypothesize and also due to inhibition of the parasympathetic reflex. On the contrary propofol has a potency to increase bradycardia by central sympatholytic effect and vagal stimulation. Hahnenkamp et al[17] explored the incidence of OCR using sevoflurane, halothane, propofol and ketamine as the main anesthetics and found the least incidence with ketamine and the highest with propofol.
Proparacaine, lignocaine, bupivacaine significantly prevented the decrease in heart rate resulting from various ocular manipulations under propofol anesthesia in the present study. Effect of topical anesthetics for prevention of OCR has been studied mainly in strabismus surgery [18,19]. Use of topical anesthetics on the cornea for the prevention of OCR and its influence on corneal healing has not been studied so far. Instillation of topical anesthetics directly on the medial rectus muscle significantly reduced the incidence of the OCR in pediatric and adult patients undergoing strabismus surgery, this involves dissection of tissues to expose the rectus muscles. Topical application of bupivacaine, procaine, and benzocaine, lidocaine, did not show any toxic effect on cornea and corneal reepithelization. But tetracaine and proparacaine are reported to have toxic effects on stromal keratocytes related not only to drug concentrations but also to time exposure. This finding raises concern that widespread use of topical anesthetic might affect the stromal wound healing. Contrary to such concern effect of single topical application of lignocaine, bupivacain and proparacain did not influence the corneal healing following superficial keratectomy in our study. The healing was comparable to the untreated control group as evident from clinical observation, histopathological study, and collagen staining and ultrastructural study of cornea.
【参考文献】
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