Related Experiment Video
Updated: Dec 26, 2025
Post-Myocardial Infarction Heart Failure in Closed-chest Coronary Occlusion/Reperfusion Model in Göttingen Minipigs and Landrace Pigs
Published on: April 17, 2021
Characterization of microminipig as a laboratory animal for pharmacological study by analyzing bepridil-induced
Yoshio Nunoi1, Mihoko Hagiwara-Nagasawa2, Ryuichi Kambayashi2
1Department of Pharmacology, Faculty of Medicine, Toho University, 5-21-16 Omori-nishi, Ota-ku, Tokyo 143-8540, Japan; Division of Cardiovascular Surgery, Department of Surgery, Faculty of Medicine, Toho University, 6-11-1 Omori-nishi, Ota-ku, Tokyo 143-8541, Japan.
Abstract:
Since microminipig is becoming attractive model for various cardiac electropharmacological applications, which may meet consideration of 3Rs. We characterized microminipigs by analyzing how multi-ionic channel inhibitor bepridil may affect their in situ hearts in comparison with dogs. Bepridil in doses of 0.3 and 3.0 mg/kg were intravenously administered over 10 min under halothane anesthesia (n = 4). Microminipigs may be less sensitive for ICaT inhibition of bepridil, whereas they are more responsive to INa, IKr and IKs suppression than dogs. This information would help predict cardiovascular effects of a drug in patients with the remodeled hearts having similar electrophysiological profile to microminipigs.
Insights
Microminipigs show distinct cardiac responses to bepridil compared to dogs, with greater sensitivity to sodium and potassium channel inhibition. This finding aids in predicting drug effects in patients with remodeled hearts.
Area of Science:
- Cardiovascular Pharmacology
- Cardiac Electrophysiology
- Animal Models in Research
Background:
- The microminipig is emerging as a valuable animal model for cardiac research, aligning with the 3Rs principles (Replacement, Reduction, Refinement).
- Understanding the electrophysiological effects of drugs in microminipigs is crucial for translational research.
Purpose of the Study:
- To characterize the effects of the multi-ionic channel inhibitor bepridil on the in situ heart of microminipigs.
- To compare the electrophysiological responses of microminipigs to bepridil with those of dogs.
Main Methods:
- Intravenous administration of bepridil (0.3 and 3.0 mg/kg) over 10 minutes in microminipigs (n=4) under halothane anesthesia.
- Assessment of bepridil's effects on cardiac ion channels (ICaT, INa, IKr, IKs) in microminipigs in comparison to dogs.
Main Results:
- Microminipigs exhibited reduced sensitivity to bepridil's inhibition of the transient calcium current (ICaT).
- Microminipigs demonstrated greater responsiveness to bepridil's suppression of the sodium current (INa) and potassium currents (IKr, IKs) compared to dogs.
Conclusions:
- Microminipigs possess a unique electrophysiological profile regarding their response to bepridil.
- This study provides valuable data for predicting the cardiovascular effects of drugs in patients with remodeled hearts exhibiting similar electrophysiological characteristics to microminipigs.
