VENTRICULAR DYSFUNCTION IN NOREPINEPHRINE-INDUCED CARDIOMYOPATHY

Cardiac dysfunction resulting from norepinephrine-induced cardiomyopat hy has not been fully investigated. This study evaluates acute and chr onic changes in systolic and diastolic function at three levels of nor epinephrine (NE)-induced injury. Rabbits were infused with saline or 2 , 4, or 6 mu g/kg/min NE for 90 min. Ventricular function was assessed immediately after infusion or at 48 hr using the isolated non-ejectin g heart preparation. Hearts were perfused at 10 ml/min/g with Krebs-He nseleit buffer. After baseline measurements, hearts were perfused with NE (10(-10) to 10(-7) M). Steady state left ventricular pressure (LVP ), +dP/dt, and -dP/dt were recorded at baseline and each NE concentrat ion. NE infusion acutely depressed baseline LV systolic function. Decr eases in LVP and +dP/dt were inversely related to dose of infused NE. By 48 hr, LVP and +dP/dt improved slightly in all NE groups but improv ement was significant only in hearts from rabbits infused with 4 mu g NE Systolic function of hearts from animals infused with 6 mu g NE rem ained depressed. Diastolic (-dP/dt) function was impaired following NE infusion when compared to saline treated hearts and did not improve w ithin 48 hr. Although baseline function is depressed, myopathic hearts increased ventricular function the same amount as normal hearts at 10 (-7) M NE. These findings demonstrate a) impairment in LV systolic and diastolic function acutely after NE infusion, b) improvement in systo lic function within 48 hr, c) ability to increase contractility in res ponse to NE is not impaired, and d) recovery of systolic function prec edes improvement in diastolic function. (C) 1994 Wiley-Liss, Inc.