Animal models to investigate drug effects on coronary physiology

Coronary blood flow is regulated by local intrinsic mechanisms according to the oxygen need of the myocardium, but the coronary circulation is also modulated by nervous, humoral, and extravascular influences. Therefore, any method used to study drug effects on the coronary circulation must take into account not only the direct effects of the drug but also any secondary drug effects that might indirectly influence the coronary vasculature. The simplest methods involve the use of isolated vessels. With these methods, the environment of the vessel can be precisely controlled, although usually only vessels larger than true resistance vessels can be studied. Isolated heart models have also been successfully employed, and in these models, effects of the drug on the myocardium must be considered. More complex models include in vivo anesthetized animal techniques with intracoronary drug administratiorl. With these models, drug effects on the coronary circulation as well as on other cardiac variables can be examined. The use of conscious, instrumented animals perhaps provides the most physiologic preparation and is very useful, particularly if intracoronary administration of drugs is employed.