TIME-DEPENDENT CHANGES IN NOREPINEPHRINE-INDUCED LEFT-VENTRICULAR DYSFUNCTION AND HISTOPATHOLOGIC CONDITION

Background: Intense activation of the sympathetic nervous system or ad ministration of high concentrations of catecholamines diminishes myoca rdial contractility and produces infarct-like lesions throughout the h eart. This study was conducted to determine whether norepinephrine-ind uced left ventricular (LV) dysfunction reverses with time and whether the histopathologic condition and the cardiac dysfunction produced by high doses of norepinephrine are causally related. Methods: Norepineph rine, 10 mu g bolus followed by 2.5 mu g/kg/min for 90 minutes, was ad ministered to conscious New Zealand white rabbits. Control rabbits (n = 8) received saline solution. LV function was evaluated either immedi ately (n = 7), on day 4 (n = 8), or on day 10 (n = 7) after norepineph rine treatment. Transverse sections from the left ventricle were then prepared for Light microscopic study. Results: Animals studied immedia tely after norepinephrine treatment demonstrated severe LV dysfunction and a decrease in global LV compliance. In contrast, LV function and compliance were normal in rabbits studied on day 4, but tissue section s from the left ventricle showed diffuse areas of inflammation. By day 10 the inflammatory process had progressed, and substantial collagen deposition had occurred. LV systolic function was normal, but a decrea se in LV compliance was evident at this time. Conclusions: The normal LV systolic function on days 4 and 10 in spite of multiple foci of inf lammation suggests (1) that norepinephrine-induced LV systolic dysfunc tion is reversible and (2) that the histologic derangements and the LV dysfunction are not causally related..