Effects of chronic infusion of norepinephrine on cardiac structure, function, and biochemistry: physiologic versus...

Ventricular hypertrophy should be divided into at least physiologic and patholgic states in order to clarify structural and functional clinical alterations. The elucidation of the structural, functional, and biochemical mechanisms of ventricular hypertrophy is vital to designing effective preventive and therapeutic measures for the hypertensive patient. Tissue markers may help differentiate pathologic from physiologic hypertrophy. Studies have established the concept that norepinephrine may be a myocardial cellular hypertrophying hormone. The studies ranged from the direct application of norepinephrine to isolated myocardial cells to the chronic subhypertensive infusion of norepinephrine into the conscious, free-roaming dog. Norepinephrine infusion can produce physiologic ventricular hypertrophy or a pathologic state of hypertrophic cardiomyopathy, the former by a three- to four-month infusion and the latter by an infusion of more than six months. The biochemical effect of subhypertensive infusion of norepinephrine was studied prior to the production of ventricular hypertrophy, thereby permitting the elucidation of the mechanism of the hypertrophic process. The biochemical stimulus for the production of myocardial cellular hypertrophy is postulated to be a diminution of cyclic AMP and a stimulation of alpha-1 receptors. Because the ventricular septum has the highest content of adenylate cyclase, which does not increase with cyclic AMP, these changes are postulated to be the biochemical basis for septal hypertrophy in the disease entity hypertrophic cardiomyopathy. A unique conscious-canine model for the production of a myocardial infarction capable of creating a controlled localized occlusion of the coronary artery is presented.(ABSTRACT TRUNCATED AT 250 WORDS)