ABSTRACT
The deleterious effects that can be exerted on myocardial structure and function by high levels of sympathomimetic amines are so significant that they were first recognized shortly after the initial characterization of epinephrine (Ziegler, 1905; Pearce, 1906; Josue, 1907; Aeisher and Loeb, 1909, 1910; Christian et al., 1911). Out of necessity, studies prior to the 1950s concentrated on the involvement of the naturally occurring compounds, norepinephrine and epinephrine. The demonstration, in 1958, that the synthetic catecholamine, isoproterenol ( 1-[3' ,4' -dihydroxyphenol]-2-isopropylaminoethanol), was capable of producing massive necrotic changes in the myocardium began to lead the focus of investigation away from the naturally occurring catecholamines (Chappel et al., 1959a). Since that time, it has become abundantly evident that myocardial damage, characterized by acute myofibrillar hypercontractile changes with reactive mononuclear inflammatory infiltration and subsequent myocardial necrosis, can be produced routinely by administration of supraphannacological doses of sympathomimetic compounds of a variety of structures and adrenoceptor activities (Chappel et al., 1959b; Rosenblum et al., 1965a; Lehr et al. , 1969). The subject of isoproterenol-induced myocardial toxicity has been recently and comprehensively reviewed (Balazs and Bloom, 1982; Rona, 1985). Isoproterenol has proved to be an enormously
valuable tool in the investigation of myocardial pathophysiology due to its ability to initiate, in a dose-dependent manner, reproducible myocardial lesions which possess many of the characteristics observed in human myocardial infarction. As a consequence, relatively little attention has been devoted in recent years to the participation of the catecholamines which normally mediate sympathetic nervous influences over myocardial function. The last major review of the cardiovascular toxicity of naturally occurring catecholamines was that of Haft (1974). The growing understanding of the importance of the central nervous system in physiological regulation of circulatory dynamics (for recent comprehensive reviews, see Randall, 1977; Galosy et al., 1981; Talman, 1985; Corr et al., 1986; Dampney, 1981; Loewy and McNeill, 1981; Pace, 1977; Swanson, 1982; Komer, 1979) has stimulated a corresponding resurgence of interest in the involvement of neural mechanisms in circulatory pathology (Talman, 1985; Sherman et al., 1987). While it is now recognized that sympathetic neurotransmission is not solely mediated by norepinephrine and epinephrine (Wilson et al., 1980; Bumstock, 1986) and that peptide hormones which are known to be co-stored and co-released with catecholamines can modulate the influences of catecholamines on myocardial function (Eiden and Ruth, 1982; Ruth et al., 1983, 1984; Schadt and Gaddis, 1985; Allen et al., 1986; McEwan et al., 1986), it seems prudent, nevertheless, to begin with a thorough recapitulation of evidence linking sympathetic catecholamines with myocardial necrotic changes.
