Positive inotropes

Inotropic agents are substances used to improve cardiac output and end-organ perfusion in severe forms of acute heart failure. However, inappropriate use of inotropic agents may be associated with severe adverse effects and death. Despite clear indications to restrict their use to acute heart failure patients presenting with signs of end-organ hypoperfusion, the current use of inotropes is very frequent and often unnecessary. This chapter reviews mechanisms of action of current and future inotropes (including catecholamines, phosphodiesterase-III inhibitors, calcium sensitizers, cardiac myosin activators, and istaroxime) and discusses their clinical use in acute heart failure.

Positive inotropes

Inotropic agents are substances used to improve cardiac output and end-organ perfusion in severe forms of acute heart failure. However, inappropriate use of inotropic agents may be associated with severe adverse effects and death. Despite clear indications to restrict their use to acute heart failure patients presenting with signs of end-organ hypoperfusion, the current use of inotropes is very frequent and often unnecessary. This chapter reviews mechanisms of action of current and future inotropes (including catecholamines, phosphodiesterase-III inhibitors, calcium sensitizers, cardiac myosin activators, and istaroxime) and discusses their clinical use in acute heart failure.

Abstract 17908: Milrinone Lacks Acute Inotropic And Lusitropic Effects Under Constant Afterload Conditions

Introduction: Phosphodiesterase III inhibitors are known to improve cardiac output in patients with heart failure. Whether this is due to a reduction in afterload, a positive inotropic effect, or an interaction of these factors is uncertain. We compared the inotropic and lusitropic effects of milrinone to those of commonly used catecholamines in a working Langendorff model under constant loading conditions. Methods: Sprague Dawley rats (n=35, 350-400 grams) were anesthetized and heparinized for cardiac explantation. The aorta and left atrium were immediately cannulated by a single experimenter. Left atrial pressure (10 mmHg) and aortic pressure (90 mmHg) were fixed. A conductance catheter (Millar) was inserted into the left ventricle. Following baseline measurements, infusions of milrinone, dopamine, dobutamine, epinephrine, or norephinephrine, alone and in commonly-used combinations, were initiated into the left atrium for 10 minute periods. Changes in cardiac output, contractility (dP/dTmax), diastolic performance (-dP/dT and Tau) relative to baseline were compared between groups by linear regression analysis. Results: Cardiac output increased in linear fashion for each of the catecholamines: Dobutamine>>Dopamine>Norepinephrine>Epinephrine (P<0.001 for each). Dobutamine, Norepinephrine, and Dopamine (P<0.05) significantly increased diastolic function, including negative dP/dT (C) and Tau (D), none of which were changed by Milrinone infusion. Conclusions: When afterload is fixed using a Starling resistor, milrinone at commonly used doses does not acutely change systolic or diastolic performance or cardiac output. It is possible that clinical improvements are due to milrinone’s vasodilatory properties.

Skeletonized Radial Artery Graft Prepared with Phosphodiesterase-III Inhibitors Indicates Favorable Results Compared with Pedicled Radial Artery Graft in Angiographic Studies

Objectives The technique used to harvest the radial artery was modified, with improved results. Skeletonized radial artery conduits prepared with phosphodiesterase-III inhibitor were compared with pedicled conduits by angiography. Methods Isolated coronary artery bypass graft surgery that used the radial artery for conduits was performed on 83 consecutive occasions from March 2003 to February 2004. The mean age of the patients was 68 ± 7 years; 65% were male. The radial arteries were harvested randomly for skeletonized (group SPD and group SPa) or pedicled (group PPD). A phosphodiesterase-III inhibitor, olprinone hydrochloride, was used as an antispastic agent during harvesting of the radial artery for both in groups SPD and PPD. Papaverine was used in group SPa. Postoperative angiograms were performed within 1 month. Diameters of the radial artery were scaled at proximal, mid, and distal sections and averaged. Optical stenosis was measured as a percent stenosis value. Results There were no significant differences among groups SPD, SPa, and PPD in morbidity or mortality rates. Graft patency rates were 97.4% in group SPD, 98.6% in group SPa, and 95.4% in group PPD (P = 0.67). Diameters of the radial artery conduits were significantly wider in group SPD compared with group PPD (P < 0.001). Spasm and stenosis were less frequent in group PPD (P < 0.05). Conclusions Skeletonized radial artery grafting prepared with a phosphodiesterase-III inhibitor indicated favorable results in angiographic studies.