Changes of electrocardiogram and hemodynamics in response to dipyridamole: In vivo comparative analyses using anesthetized beagle dogs and microminipigs

• Published in: Journal of pharmacological sciences 2018-02, Vol.136 (2), p.86-92
• Main Authors: Ando, Kentaro, Takahara, Akira, Nakamura, Yuji, Wada, Takeshi, Chiba, Koki, Goto, Ai, Lubna, Nur Jaharat, Hagiwara-Nagasawa, Mihoko, Izumi-Nakaseko, Hiroko, Hoshiai, Kiyotaka, Akie, Yasuki, Naito, Atsuhiko T., Sugiyama, Atsushi
• Format: Article
• Language: English
• Subjects: Anesthesia; Animals; Collateral arteries; Collateral Circulation - drug effects; Coronary Circulation - drug effects; Coronary steal; Dipyridamole; Dipyridamole - administration & dosage; Dipyridamole - pharmacology; Dogs; Dose-Response Relationship, Drug; Electrocardiography - drug effects; Female; Hemodynamics - drug effects; Infusions, Intravenous; Male; Models, Animal; ST-segment depression; Swine; Swine, Miniature
• ISSN: 1347-8613; 1347-8648
• DOI: 10.1016/j.jphs.2018.01.002

Microminipigs are expected as a novel animal model for cardiovascular pharmacological experiments. Since inherent vulnerability of coronary circulation of microminipigs has not been characterized, we performed dipyridamole-stress test to both microminipigs and beagle dogs, and compared the results. Dipyridamole in doses of 0.056 and 0.56 mg/kg were intravenously infused over 10 min (n = 4 for each animal). Dipyridamole decreased the systolic/diastolic blood pressures and double product in dogs as well as in microminipigs; but it did not significantly alter the heart rate or the global balance between the myocardial oxygen demand and supply in either animal. While organic coronary arterial stenosis was not detected in either animal, dogs have well-developed epicardial intracoronary networks unlike microminipigs. Like in humans, dipyridamole did not affect the ST segment of microminipigs, whereas it substantially depressed that in dogs. The results indicate the onset of subendocardial ischemia by dipyridamole in dogs may be partly associated with their well-developed native coronary collateral channels. Microminipigs would be more useful to evaluate the drugs which may affect the coronary circulation in the pre-clinical study than dogs.