Cardiovascular effects of increasing doses of glycopyrrolate in anesthetized New Zealand white rabbits.

OBJECTIVE

To characterize the cardiovascular effects of 3 increasing doses of glycopyrrolate in healthy rabbits anesthetized with isoflurane.

METHODS

9 healthy 1-year-old female New Zealand white rabbits were anesthetized with isoflurane and received increasing doses of glycopyrrolate at low dose (LD; 0.025 mg/kg), medium dose (MD; 0.05 mg/kg), and high dose (HD; 0.1 mg/kg) IV. Heart rate was recorded at baseline and 3, 5, 10, 20, and 30 minutes after administration of each dose. An arterial blood sample was collected to measure plasma glycopyrrolate concentrations at baseline and 3 and 30 minutes after administration of each dose. Analysis of plasma glycopyrrolate concentrations was performed using LC-MS-MS.

RESULTS

The HD led to a significantly higher heart rate δ value than LD and MD only at 3 minutes (all P < .003). The HD caused significantly higher systolic arterial pressure and mean arterial pressure δ values at 3, 5, 20, and 30 minutes (P < .05) and diastolic arterial pressure at 3, 20, and 30 minutes (P < .05) than LD. The MD caused a significantly higher diastolic arterial pressure δ value at 20 and 30 minutes (P < .05) and mean arterial pressure at 5, 20, and 30 minutes (P < .05) than LD. The mean plasma concentration that elicited a significant increase in heart rate was 62 ± 16.11 ng/mL.

CONCLUSIONS

A brief increase (< 5 minutes) in HR in nonbradycardic rabbits was observed with 0.1 mg/kg of glycopyrrolate during isoflurane anesthesia.

CLINICAL RELEVANCE: Even at HDs, clinical effects of glycopyrrolate in rabbits appear very short lived.