Ventricular dysfunction in norepinephrine-induced cardiomyopathy

Cardiac dysfunction resulting from norepinephrine-induced cardiomyopathy has not been fully investigated. This study evaluates acute and chronic changes in systolic and diastolic function at three levels of norepinephrine (NE)-induced injury. Rabbits were infused with saline or 2, 4, or 6 micrograms/kg/min NE for 90 min. Ventricular function was assessed immediately after infusion or at 48 hr using the isolated non-ejecting heart preparation. Hearts were perfused at 10 ml/min/g with Krebs-Henseleit 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 concentration. NE infusion acutely depressed baseline LV systolic function. Decreases 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 improvement was significant only in hearts from rabbits infused with 4 micrograms NE. Systolic function of hearts from animals infused with 6 micrograms NE remained depressed. Diastolic (-dP/dt) function was impaired following NE infusion when compared to saline treated hearts and did not improve within 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 systolic function within 48 hr, c) ability to increase contractility in response to NE is not impaired, and d) recovery of systolic function precedes improvement in diastolic function.