Effects of Anisodine Hydrobromide on the Cardiovascular and Respiratory Functions in Conscious Dogs

Abstract

Purpose

Anisodine hydrobromide (Ani) is isolated from the medicinal plant Anisodus tanguticus (Maxim.) Pascher for clinical use. Although considerable research regarding Ani has been reported, the safety profiles of Ani are currently unknown. This study investigated the cardiorespiratory effects of Ani in conscious dogs to provide clinicians a detailed safety profile of Ani on the cardiorespiratory system.

Materials and Methods

Using the Latin square design, the study was divided into six phases, where in each phase, six telemetered beagle dogs received one dose of normal saline or sotalol hydrochloride or Ani (0.1, 0.4, 1.6, or 6.4 mg/kg). Electrocardiogram, blood pressure (BP) and respiratory parameters were collected before and after administration for 24 hours. Statistical comparisons were performed at scheduled time-points.

Results

The heart rate was significantly increased, PR and QT_CV intervals were significantly shortened in Ani 0.4, 1.6, 6.4 mg/kg treatment group after drug administration. Compared with the saline group, a significant increase in heart rate and shortening of PR, QT_CV intervals were observed in the Ani 1.6, 6.4 mg/kg treatment groups from 5 min to 4 h time-points. Diastolic and mean BP were significantly increased in Ani 1.6, 6.4 mg/kg from 1 h to 2 h time-points compared to those of the saline control. Accelerated breathing was observed in the first 20 min after Ani 0.4, 1.6, and 6.4 mg/kg treatment, although not statistically significant. Furthermore, no significant differences were observed in any of the corresponding indexes of Ani 0.1 mg/kg treatment group at different time-points compared to those of the saline group.

Conclusion

Ani may have adverse effects on the cardio-respiratory systems of dogs at doses above 0.4 mg/kg, whereas Ani 0.1 mg/kg was devoid of potentially deleterious effects on cardiorespiratory function.

Keywords:

• anisodine hydrobromide
• electrocardiogram
• blood pressure
• cardio-respiratory function
• telemetered dogs
• safety

Funding

This study was supported by the science and technology support plan of Sichuan province under Grant (No. 2016SZ0027).

Abbreviations

Ani, anisodine hydrobromide; BP, blood pressure; ICH, International Council for Harmonization; CFDA, China Food and Drug Administration; ECG, Electrocardiogram; Sol, sotalol hydrochloride; NS, normal saline; SYS, systolic blood pressure; DIA, diastolic blood pressure; MEAN, mean arterial blood pressure; TV, tidal volume; MV, minute ventilation volume; BR, breath rate; SOP, standard operating procedure; PND, phrenic nerve discharges.

Disclosure

Yunlu Liu, Lin Wang, Feng Wanand Na Yang report grants from the Science and Technology support plan of Sichuan province, during the conduct of the study. The authors report no other potential conflicts of interest in this work.