Time-dependent changes in norepinephrine-induced left ventricular dysfunction and histopathologic condition

Intense activation of the sympathetic nervous system or administration of high concentrations of catecholamines diminishes myocardial contractility and produces infarct-like lesions throughout the heart. This study was conducted to determine whether norepinephrine-induced 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.

Norepinephrine, 10 microg bolus followed by 2.5 microg/kg/min for 90 minutes, was administered to conscious New Zealand white rabbits. Control rabbits (n=8) received saline solution. LV function was evaluated either immediately (n=7), on day 4 (n=8), or on day 10 (n=7) after norepinephrine treatment. Transverse sections from the left ventricle were then prepared for light microscopic study.

Animals studied immediately 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 sections 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 decrease in LV compliance was evident at this time.

The normal LV systolic function on days 4 and 10 in spite of multiple foci of inflammation suggests (1) that norepinephrine-induced LV systolic dysfunction is reversible and (2) that the histologic derangements and the LV dysfunction are not causally related.