The differential effects of positive inotropic and vasodilator therapy on diastolic properties in patients with congestive cardiomyopathy.

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Abstract
Symptoms of congestive heart failure frequently reflect abnormalities in both systolic and diastolic performance. While much work has been reported regarding the mechanisms by which positive inotropic and vasodilator therapy affect systolic performance, little is known about their effect on diastolic function. In 12 patients with diffuse congestive cardiomyopathy micromanometer left ventricular and aortic pressure measurements were recorded simultaneously with two-dimensionally targeted M mode echocardiograms and thermodilution-determined cardiac output. Each patient received dopamine (2, 4, and 6 .mu.g/kg/min), and dobutamine (2, 6, and 10 .mu.g/kg/min), and 10 received nitroprusside (0.125 to 2.0 .mu.g/kg/min). Baseline hemodynamics were characterized by low cardiac index (2.1 .+-. 0.7 liter/min/m2, mean .+-. SD), high left ventricular end-diastolic pressure (24 .+-. 10 mm Hg), and increased end-diastolic (6.8 .+-. 1.0 cm) and end-systolic dimensions (6.0 .+-. 1.0 cm). All patients had abnormal left ventricular pressure decay with a prolonged time constant (67 .+-. 20 msec) and reduced peak diastolic lengthening rates. Dopamine and dobutamine decreased the time constant of relaxation and increased the peak lengthening rate. Dobutamine also reduced the minimum diastolic pressure from 14 .+-. 7 to 10 .+-. 9 mm Hg (p < .01); neither drug reduced end-diastolic pressure. In fact, dopamine elevated end-diastolic pressures in seven patients, despite more rapid pressure decay. Diastolic pressure-dimension relations after dopamine and dobutamine showed a leftward shift with a reduced end-systolic chamber size, but no significant changes in passive chamber stiffness. Nitroprusside decreased left ventricular minimum diastolic pressure by 4 .+-. 2 mm Hg and end-diastolic pressure by 7 .+-. 4 mm Hg (p < .01). It did not consistently accelerate left ventricular pressure decay at the doses tested. The decreased end-diastolic pressure with nitroprusside was due to a reduced end-diastolic dimension in five patients. In the other patients, all of whom had elevated right atrial pressures, diastolic pressure-dimension relations showed a parallel downward shift after nitroprusside. Thus, positive inotropic therapy with .beta.1-adrenoceptor agonists enhances early diastolic distensibility by accelerating relaxation, augmenting filling, and reducing end-systolic chamber size. Vasodilator therapy is much more effective in lowering diastolic pressures. In some patients this is due to a reduction in extrinsic restraint of the pericardium and/or right ventricular interaction, while in others it simply reflects a decrease in chamber size without alterations in ventricular passive chamber properties.