Rational use of inotropes

Circulation, 1988

Clinical trials in patients with dilated cardiomyopathy (DCM) have shown a wide disparity in the hemodynamic responses to positive inotropic therapy. In addition, the response of the failing left ventricle to positive inotropic agents reflects the net interaction of multiple factors, including the magnitude of contractile abnormality and compensatory mechanisms. In the current study, left ventricular geometry, loading conditions, and contractile state were assessed in 13 patients with nonischemic DCM with the use of simultaneous high-fidelity pressure measurements and echocardiographic recordings. Comparisons were made with echocardiographic and calibrated carotid pulse data acquired in nine age-matched normal subjects. The patients with DCM were divided according to the left ventricular end-diastolic wall thickness-to-dimension ratio into groups with "appropriate" hypertrophy (i.e., < 2 SDs from mean normal; n = 5; group 1) and "inadequate" hypertrophy (i.e., > 2 SDs from mean normal; n =8; group 2). Age, New York Heart Association functional class, left ventricular wall mass index, and left ventricular end-diastolic pressure and dimension were similar for the DCM groups. Baseline left ventricular afterload (defined as circumferential end-systolic wall stress, COes) was 168% and 203% greater than normal in groups 1 and 2, respectively. The administration of the 13-adrenoceptor agonist dobutamine decreased left ventricular afterload by 12% in the normal subjects and by 10% in group 1 patients, while augmenting afterload by 5% in group 2 patients. The latter response occurred despite a 17% fall in systemic vascular resistarnce. Overall left ventricular performance, as assessed by the rate-corrected mean velocity of fiber shortening (Vcfc), was related to left ventricular afterload (i.e., Ces). The resultant Qes -Vcfc relationship, a sensitive measure of left ventricular contractility, was determined over a wide range of afterload conditions generated by methoxamine (normal subjects) or nitroprusside (DCM). Baseline left ventricular contractile state was 61% of normal for group 1 and 44% of normal for group 2. The contractile response to dobutamine infusion was 52% of normal for group 1 and only 22% of normal for group 2. Thus, positive inotropic therapy with dobutamine in patients with DCM is limited by (1) an attenuated contractile response and (2) elevated left ventricular afterload, which may be augmented further during its administration. The ability to separate and quantify abnormalities in left ventricular geometry, loading conditions, and contractile state allows a more thorough interpretation of the hemodynamic responses to a positive inotropic agent and may be useful in determining which patients with heart failure would benefit from treatment with specific cardiotonic agents. trials have demonstrated a wide disparity in the hemodynamic responses to these agents even when administered in the same doses to patients with similar symptoms.3 This is due to numerous factors, including (1) interpatient differences in left ventricular contractile state, preload, afterload, heart rate, chamber geometry, and ventricular hypertrophy,6' 7 (2) the variable activation of cardiac and peripheral vascular receptors by the same pharmacologic agent, and (3) the load dependency of traditional measures of overall left ventricular performance (e.g., cardiac output and ejection fraction) as well as their inability to distinguish 625 by guest on July 11, 2011 http://circ.ahajournals.org/ Downloaded from

Journal of applied physiology (Bethesda, Md. : 1985), 2016

Inotropic medications are routinely used to increase cardiac output and arterial blood pressure during critical illness. However, few comparative data exist between these medications, particularly independent of their effects on venous capacitance and systemic vascular resistance. We hypothesized that an isolated working heart model that maintained constant left atrial pressure and aortic blood pressure could identify load-independent differences between inotropic medications. In an isolated heart preparation, the aorta and left atrium of Sprague Dawley rats were cannulated and placed in working mode with fixed left atrial and aortic pressure. Hearts were then exposed to common doses of a catecholamine (dopamine, epinephrine, norepinephrine, or dobutamine), milrinone, or triiodothyronine (n = 10 per dose per combination). Cardiac output, contractility (dP/dtmax), diastolic performance (dP/dtmin and tau), stroke work, heart rate, and myocardial oxygen consumption were compared during...

Circulation, 1986

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 gg/kg/min), and dobutamine (2, 6, and 10 ,ug/kg/min), and 10 received nitroprusside (0.125 to 2.0 gg/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 < .0 1). 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 /31-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. Circulation 74, No. 4, 815-825, 1986. AS OUR UNDERSTANDING of the pathophysiology of the heart failure syndrome has improved, certain classes of drugs have assumed prominent roles in its treatment. The administration of vasodilating agents is

International Journal of Cardiology, 1995

The phosphodiesterase (PDE) III inhibitor, E-1020 (loprinone hydrochloride), has positive inotropic and vasodilating effects. This study evaluated the positive inotropic effect of intracoronary E-1020 in eight patients with coronary artery disease and hypertensive heart disease. A direct intracoronary infusion of the PDE III inhibitor minimizes its vasodilating effect. After baseline hemodynamic measurements and coronary arteriography, a micromanometer-tipped SF conductance catheter was introduced into the left ventricle to determine the hemodynamic effects of E-1020. Saline and vehicle were infused into the left main coronary artery at a rate of 2 ml/min. The dose of intracoronary E-1020 increased from 2.5 to 5.0 and 7.5 pg/min. The inotropic effect of E-1020 was defined as the change in the slope of the end-systolic pressure-volume relationship (E,,,), which was independent of afterload and preload. E,,, significantly increased at infusion rates of 7.5 &min from control. Peak +dP/dt increased at an infusion rate of 5.0 &mm or higher, while left-ventricular end-diastolic pressure (LVEDP) decreased significantly at a rate of 5.0 and 7.5 &min. Intracoronary infusion of E-1020 at a rate of 2.5 &min produced a plasma concentration of 20 rig/ml, which was identical to the minimum effective plasma concentration seen in previous study by intra venous infusion. However, at a plasma concentration of 20 r&ml, E-1020 has more vasodilating effects than inotropic effects. Clinically, E-1020 appears to have a positive inotropic effect that depends on the extent of myocardial perfusion.

Journal of Cardiothoracic Anesthesia, 1990

The American Journal of Cardiology, 1984

The acute hemodynamic effects of intravenous diltiazem were studied in 8 patients with coronary artery disease, left ventricular (LV) failure (New York Heart Association functional class III), a rest ejection fraction (EF) less than 40% or a cardiac index less than 2.4 liters/min/m 2. Hemodynamic measurements and LV angiograms were performed at rest before and after the administration of diltiazem, 0.5 mg/kg, administered at a speed of 5 mg/min. Diltiazem treatment induced a decrease in heart rate from 68 -4-12 to 55 4-9 beats/min (p <0.001 ). Mean aortic pressure decreased from 94 4-14 to 81 -I-15 mm Hg (p <0.05). Thus, the pressure-rate product significantly decreased under the influence of the drug, from 8,791 -t-2,465 to 6,342 -4-1,808 beats mm Hg/min, (p <0.001). Diltiazem induced no significant change of LV end-diastolic pressure, pulmonary wedge pressure, cardiac index and LV stroke work index. Systemic vascular resistance decreased (p <0.01), whereas pulmonary vascular resistance showed no change. End-systolic volume diminished (p <0.02), which accounts for the increase of stroke volume and ejection fraction (p <0.001). Disorders of regional contractility were not aggravated by diltiazem, and even improved in individual cases. Thus, intravenous diltiazem may be used safely in patients with heart failure. However, in view of the marked bradycardic effects seen in some cases, heart rate should be carefully monitored.

Critical Care Medicine, 2006

2013

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2003

and it is a condition of accessing publications that users recognise and abide by the legal requirements associated with these rights. • Users may download and print one copy of any publication from the public portal for the purpose of private study or research. • You may not further distribute the material or use it for any profit-making activity or commercial gain • You may freely distribute the URL identifying the publication in the public portal ? Overige leden promotiecommissie: prof.dr. J. Baan prof.dr. A.V.G. Bruschke prof.dr. C.J.A. van Echteld prof.dr. W.H. van Gilst prof.dr. N. Westerhof CONTENTS Chapter 1 Introduction Diastolic left ventricular dysfunction: The epicenter of the heart failure syndrome 1.1 General Introduction 1.2 Heart failure and left ventricular ejection fraction 1.3 Left ventricular diastolic distensibility and heart failure 1.4 Stroke volume reserve and heart failure symptoms 1.5 Diastolic pressure-volume relationship and left ventricular diastolic dysfunction Chapter 2 Diastolic left ventricular dysfunction and an upward shift of the left ventricular diastolic pressure-volume relationship 2.1 Comparative effects of pacing-induced and balloon coronary occlusion ischemia on left ventricular diastolic function in man Circulation. 1991;84(1):211-22 2.2 Comparative effects of ischemia and hypoxemia on left ventricular systolic and diastolic function in humans Circulation. 1993;88(2):461-71 2.3 Comparative effects of ischemia and hypoxemia on left ventricular diastolic function in humans In: Lorell B, Grossman W, editors. Diastolic relaxation of the heart. Boston: Kluwer Academic Publishers, 1994: 303-321 2.4 Deficient acceleration of left ventricular relaxation during exercise after heart transplantation