Milrinone enhances cytosolic calcium transient and contraction in rat cardiac myocytes during beta-adrenergic stimulation

Raffaeli, S.; Ferroni, C.; Spurgeon, Harold A.; Capogrossi, Maurizio C.

doi:10.1016/0167-5273(89)90095-8

Cited by 13 publications

(4 citation statements)

References 15 publications

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“…Myocytes were stimulated at 1 Hz via platinum electrodes connected to a Grass Telefactor S48 stimulator (West Warwick, RI). As Mil alone did not elicit a functional effect (as previously demonstrated; Raffaeli et al, 1989 ), following baseline, all cells were perfused with a low dose of ISO (0.1 nM) to increase intracellular cAMP to enable MIL to have an effect, but yet, 0.1 nM ISO did not have a significant function effect alone. Both CXL-1020 and Mil solutions also contained 0.1 nM ISO.…”

Section: Methodsmentioning

confidence: 74%

CXL-1020, a Novel Nitroxyl (HNO) Prodrug, Is More Effective than Milrinone in Models of Diastolic Dysfunction—A Cardiovascular Therapeutic: An Efficacy and Safety Study in the Rat

et al. 2017

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The nitroxyl (HNO) prodrug, CXL-1020, induces vasorelaxation and improves cardiac function in canine models and patients with systolic heart failure (HF). HNO's unique mechanism of action may be applicable to a broader subset of cardiac patients. This study investigated the load-independent safety and efficacy of CXL-1020 in two rodent (rat) models of diastolic heart failure and explored potential drug interactions with common HF background therapies. In vivo left-ventricular hemodynamics/pressure-volume relationships assessed before/during a 30 min IV infusion of CXL-1020 demonstrated acute load-independent positive inotropic, lusitropic, and vasodilatory effects in normal rats. In rats with only diastolic dysfunction due to bilateral renal wrapping (RW) or pronounced diastolic and mild systolic dysfunction due to 4 weeks of chronic isoproterenol exposure (ISO), CXL-1020 attenuated the elevated LV filling pressures, improved the end diastolic pressure volume relationship, and accelerated relaxation. CXL-1020 facilitated Ca2+ re-uptake and enhanced myocyte relaxation in isolated cardiomyocytes from ISO rats. Compared to milrinone, CXL-1020 more effectively improved Ca2+ reuptake in ISO rats without concomitant chronotropy, and did not enhance Ca2+ entry via L-type Ca2+ channels nor increase myocardial arrhythmias/ectopic activity. Acute-therapy with CXL-1020 improved ventricular relaxation and Ca2+ cycling, in the setting of chronic induced diastolic dysfunction. CXL-1020's lusitropic effects were greater than those seen with the cAMP-dependent agent milrinone, and unlike milrinone it did not produce chronotropy or increased ectopy. HNO is a promising new potential therapy for both systolic and diastolic heart failure.

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Section: Methodsmentioning

confidence: 74%

CXL-1020, a Novel Nitroxyl (HNO) Prodrug, Is More Effective than Milrinone in Models of Diastolic Dysfunction—A Cardiovascular Therapeutic: An Efficacy and Safety Study in the Rat

et al. 2017

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“…This may indicate that baseline b-adrenergic stimulation (i.e., endogenous catecholamines) is required to detect the cardiac activity of atenolol or other beta-blockers, and hence co-culture systems containing cardiac endothelial cells might be more promising biological systems to use in this case, as they are able to synthesize and release catecholamines, such as adrenaline (Sorriento et al, 2012). A similar explanation may explain the results for milrinone, which induced no increase in the average amplitude of the calcium transients, given that enhancement in the baseline b-adrenergic stimulation is required for this compound to induce a positive inotropic action in vitro (Raffaeli et al, 1989).…”

Section: Discussionmentioning

confidence: 92%

Deriving waveform parameters from calcium transients in human iPSC-derived cardiomyocytes to predict cardiac activity with machine learning

et al. 2022

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“…In canine cardiac myocytes, a significant inotropic effect was observed with no increase in the Ca-transient at concentrations of EMO 57033 up to 3 jJ.moljl [50], although at higher concentrations (5 jJ.moljl and above), a small increase in the systolic Ca-transient was observed, probably due to some residual POE-inhibitory effect. In rat myocardium however, there is low POE activity compared with other species such that any residual POE-inhibitory effect of EMO 57033 would be minimized [56,57]. It is likely therefore, that at concentrations up to 5 u moly'l, the inotropic effect of EMO 57033 is exerted predominantly by increasing the myofilament response to Ca [55].…”

Section: Emd 57033 and Wall-stress-induced Arrhythmiamentioning

confidence: 99%

Experimental Studies on Myocardial Stretch and Ventricular Arrhythmia in Hypertrophied and Non-Hypertrophied Hearts

Evans

DALTON

Levi

2000

European Journal of Cardiovascular Risk

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Hypertension affects about 5% of western populations and in the majority of cases it is of unknown aetiology. It exposes the heart to greater levels of myocardial stretch as a result of increased systolic pressure and peripheral resistance. Under certain circumstances myocardial stretch may trigger arrhythmias but the mechanisms and clinical importance of this phenomenon are unclear. This article outlines the risks of sudden cardiac death conferred by hypertension and left ventricular hypertrophy, presents the results of experiments using an animal model of myocardial stretch and discusses some possible mechanisms underlying stretch-induced arrhythmias which may be important in hypertensive patients. j Cardiovasc Risk 7:163-175

show abstract

Milrinone enhances cytosolic calcium transient and contraction in rat cardiac myocytes during beta-adrenergic stimulation

Cited by 13 publications

References 15 publications

CXL-1020, a Novel Nitroxyl (HNO) Prodrug, Is More Effective than Milrinone in Models of Diastolic Dysfunction—A Cardiovascular Therapeutic: An Efficacy and Safety Study in the Rat

CXL-1020, a Novel Nitroxyl (HNO) Prodrug, Is More Effective than Milrinone in Models of Diastolic Dysfunction—A Cardiovascular Therapeutic: An Efficacy and Safety Study in the Rat

Deriving waveform parameters from calcium transients in human iPSC-derived cardiomyocytes to predict cardiac activity with machine learning

Experimental Studies on Myocardial Stretch and Ventricular Arrhythmia in Hypertrophied and Non-Hypertrophied Hearts

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