Experimental heart failure produced by rapid ventricular pacing in the dog

Abstract

To study the complex pathophysiology of chronic heart failure and the efficacy of pharmacologic interventions, a number of experimental models have been developed. ~ Most animal models used previously were ones of surgically induced volume or pressure overload, myocardial ischemia, and toxic depression of cardiac function. Many of these models had major limitations, for example, requiring major surgery and/or thoracotomy deranging neurohormonal systems and cardiovascular reflexes, exhibiting only left ventricnlar (LV) hypertrophy or dysfunction that lacked essential features of congestive heart failure (such as elevated filling pressures, low cardiac output, activation of neurohumoral systems, and systemic vasoconstriction), producing only rightsided heart failure, or causing systemic damage by cardiotoxic agents. In many preparations, the degree of damage to the heart and the resulting state of heart failure are not predictable. In addition, models in very small animals are limited due to the restricted number of functional and humoral parameters to be assessed. In the last decade, because of its apparent advantages over many other preparations, the model of pacing-induced heart failure has become one of the most widely used and best-studied models of heart failure. This model was developed in dogs and has most often been used in that species. Recently, it was modified for other species, such as sheep, s,6 pigs, 7,8 rabbits, 9,~° and rats. H Because most of the literature on the pacing model is based on the canine model and because variations between species and differing techniques cannot be excluded, our review will focus mainly on experiments performed in dogs. A model of pacing-induced heart failure was briefly reported for the first time in 196272 Rapid atrial stimulation in dogs was performed using external pacemakers. Due to largely varying atrioventricular (AV) conduction,