Epinephrine Affects Pharmacokinetics of Ropivacaine Infiltrated Into Palate
Pulpal anesthesia success rates for ropivacaine following maxillary infiltration anesthesia seem to be low. We investigated the hypothesis that the addition of epinephrine would affect the pharmacokinetics of ropivacaine by retaining ropivacaine in the mucosa of the injected area through the time-dependent distribution of ropivacaine in the rat maxilla and serum following maxillary infiltration anesthesia using 3H-labeled ropivacaine. We then examined the vasoactivity of ropivacaine with or without epinephrine on local peripheral blood flow. The addition of epinephrine to ropivacaine increased ropivacaine concentrations in the palatal mucosa and adjacent maxilla by more than 3 times that of plain ropivacaine at 20 minutes. By observing the autoradiogram of 3H-ropivacaine, plain ropivacaine in the maxilla was remarkably reduced 20 minutes after injection. However, it was definitely retained in the palatal mucosa, hard palate, adjacent maxilla, and maxillary nerve after the administration with epinephrine. Ropivacaine with epinephrine significantly decreased labial blood flow. This study suggests that 10 μg/mL epinephrine added to 0.5% ropivacaine could improve anesthetic efficacy and duration for maxillary infiltration anesthesia over plain ropivacaine.
Divisions of the maxilla. The palatal mucosa was removed from the areas of A and B. The maxilla part from the front end of the zygomatic arch to the end of the third molar was divided into 2 parts (C, D) along the solid line (—). The asterisk indicates the site of injection. The broken line (—) shows the position of a frontal section for the 3H-autoradiogram. (A) Right palatal mucosa. (B) Left palatal mucosa. (C) Right maxilla part (including right molars; the zygomatic arch was removed). (D) Left maxilla part (including left molars; the zygomatic arch was removed).
Measurement of blood flow rate. The schema shows the locations of a probe of the flowmeter and injection of the agents. The blood flow rate was measured by the laser Doppler flowmetry with a contact-type probe. The probe was placed on the left upper lip under general anesthesia. Twenty microliters of each agent (0.9% NaCl [control], 10 μg/mL epinephrine, 0.5% ropivacaine, or 0.5% ropivacaine with 10 μg/mL epinephrine) was injected into the left upper lip adjacent to the angle of mouth with a 31-gauge needle. The blood flow rate was measured for 60 minutes after the injection of each solution (n = 4).
Distribution and concentration of ropivacaine in rat maxilla. After 0.5% 3H-ropivacaine was infiltrated into the right palatal mucosa proximal to the first molar without (○) or with (•) 10 μg/mL epinephrine, the radioactivity in (A) right palatal mucosa, (B) left palatal mucosa, (C) right maxilla part, or (D) left maxilla part was measured with the liquid scintillation counter. The concentration (ng/mg wet weight) of ropivacaine was calculated by the specific radioactivity. Data are mean ± SD (n = 7). *P < .05 versus the ropivacaine group.
Autoradiogram of 3H-ropivacaine in a frontal section of the maxilla. 3H-ropivacaine of 0.5% was infiltrated into the right palatal mucosa proximal to the first molar without (the left line) or with (the right line) 10 μg/mL epinephrine. The maxilla removed 2, 20, 40, and 60 minutes after infiltration was frozen and sectioned at the injection point with the cryostat microtome. The section of 20 μm was exposed for 40 days at room temperature to MS-film with sensitization paper. Then, the sections were stained with 0.25% eosin. The stained section was put on top of the autoradiogram of MS-film and was scanned by a scanner with transmitted light.
Quantitative analysis of 3H-autoradiogram. The section used for autoradiography in Figure 3 was exposed to the imaging plate also for 40 days at room temperature. Quantitative analysis of the 3H-autoradiogram in the plate was performed by an image analyzer. 3H-ropivacaine was infiltrated into the palatal mucosa without (○) or with (•) epinephrine. The amount of autoradiographic signal in the section at 2 minutes after the injection of ropivacaine was indicated as 100 (2953 ± 18 dpm/section). The maximal amount of the signal existed in the maxilla at 2 minutes after the injection of ropivacaine with epinephrine. The radioactivity in this section was 4264 ± 29 dpm/section. Data are mean ± SD (n = 4). *P < .05 versus the ropivacaine group.
Concentration of radioactivity derived from 3H-ropivacaine in the serum. After 0.5% 3H-ropivacaine was infiltrated into the right palatal mucosa proximal to the first molar, without (○) or with (•) 10 μg/mL epinephrine, the radioactive concentration (dpm/mL) in the serum was measured with the liquid scintillation counter. Data are mean ± SD (n = 7). *P < .05 between the two groups.
Effect of ropivacaine on the blood flow rate of rat upper lip. After 20 μL of 0.9% NaCl (○), 0.5% ropivacaine (•), 10 μg/mL epinephrine (△), or ropivacaine with epinephrine (▴) was injected to the rat upper left lip, the labial blood flow rate was measured by a laser Doppler flow meter (ALF21, ADVANCE) with a contact-type probe. Data are mean ± SD (n = 4). *P < .05 epinepherine versus ropivacaine with epinephrine.
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