Effect of inotropic and vasodilator therapy on left ventricular diastolic filling in dogs with severe left ventricular dysfunction

Abstract

Inotropic and vasodilator therapy for congestive heart failure improve left ventricular systolic performance by different mechanisms. However, the nature and extent to which diastolic filling is altered have not been well described. Acute severe left ventricular dysfunction was induced in 21 dogs by severe left ventricular global ischemia produced by left main coronary artery microsphere embolization until left ventricular end-diastolic pressure was ≥18 mm Hg. Dobutamine was infused in seven dogs until the peak positive first derivative of left ventricular pressure (dP/dt) increased by ≥33%. Nitroprusside was infused in seven dogs until left ventricular end-diastolic pressure was <15 mm Hg. Seven dogs were observed for 1 h after the induction of acute severe left ventricular dysfunction and served as the control group.In all groups of dogs, severe left ventricular dysfunction resulted in left ventricular dilation, reduction in area ejection fraction, elevation of left ventricular end-diastolic pressure and an early redistribution of diastolic filling (increased 1/3 and 1/2 filling fractions) despite a markedly abnormal tune constant of relaxation. No changes were noted in any variable after 1 h of observation in the seven control dogs. Nitroprusside reduced left ventricular size and filling pressure, increased cardiac output, improved relaxation and redistributed diastolic filling to later in diastole as characterized by a reduced 1/3 filling fraction (19.4 ± 7.4% versus 51.4 ± 10%, p < 0.001). The pressure-area curve was shifted downward and leftward. Dobutamine increased cardiac output, increased area ejection fraction, reduced end-systolic volume, improved relaxation and redistributed diastolic filling to later in diastole (1/3 filling fraction 18.7 ± 7.4% versus 44.2 ± 8.0%, p < 0.001). The pressure-area curve was shifted downward and leftward initially (smaller end-systolic volume and lower left ventricular minimal pressure).In conclusion, despite differing mechanisms utilized to improve systolic and diastolic performance, diastolic filling was altered in a similar fashion by both dobutamine and nitroprusside. The nonspecificity of this alteration may be related to similar influences of improved relaxation and reduced pericardial restraining forces on the diastolic filling pattern.