Tolerability of extended duration intravenous milrinone in patients hospitalized for advanced heart failure and the usefulness of uptitration of oral angiotensin-converting enzyme inhibitors

LaForest, Sharon; Shubert, Joanne; Mendoza, Bernardo; Flores, Isabella Victória Casco; Eisen, Howard J.; Piña, Ileana L.

doi:10.1016/s0002-9149(99)00461-0

Cited by 23 publications

(8 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In acute cardiac decompensation occurring in heart failure patient receiving "-AR blocker, parenteral PDE inhibitor infusion is more beneficial as compared to acute administration of dobutamine, a " 1 -AR agonist [9][10][11][12][13][14][15][16]. In decompensated patients, long-term intravenous PDE inhibitor administration allows the uptitration of oral angiotensin-converting enzyme inhibitors or other vasodilators without significant hypotension [17,18]. In chronic heart failure patients starting treatment with "-AR blocker, a concomitant PDE inhibitor administration prevents transient reduction in ventricular systolic function due to withdrawal of inotropic support provided by resting adrenergic tone [19][20][21][22].…”

mentioning

confidence: 99%

Myocardial Phosphodiesterases and Regulation of Cardiac Contractility in Health and Cardiac Disease

Osadchii

2007

Cardiovasc Drugs Ther

View full text Add to dashboard Cite

Phosphodiesterase (PDE) inhibitors are potent cardiotonic agents used for parenteral inotropic support in heart failure. Contractile effects of these agents are mediated through cAMP-protein kinase A-induced stimulation of I (Ca2+) which ultimately results in increased Ca(2+)-induced sarcoplasmic reticulum Ca(2+) release. A number of additional effects such as increases in sarcoplasmic reticulum Ca(2+) stores, stimulation of reverse mode Na(+)-Ca(2+) exchange, direct or cAMP-mediated effects on sarcoplasmic reticulum ryanodine receptor, stimulation of the voltage-sensitive sarcoplasmic reticulum Ca(2+) release mechanism, as well as A(1) adenosine receptor blockade could contribute to positive inotropic responses to PDE inhibitors. Moreover, some PDE inhibitors exhibit Ca(2+) sensitizer properties as they could increase the affinity of troponin C Ca(2+)-binding sites as well as reduce Ca(2+) threshold for thin myofilament sliding and facilitate cross-bridge cycling. Inotropic responses to PDE inhibitors are significantly reduced in cardiac disease, an effect largely attributed to downregulation of cAMP-mediated signalling due to sustained sympathetic activation. Four PDE isoenzymes (PDE1, PDE2, PDE3 and PDE4) are present in myocardial tissue of various mammalian species, of which PDE3 and PDE4 are particularly involved in regulation of cardiac myocyte contraction. PDE cAMP-hydrolysing activity is preserved in compensated cardiac hypertrophy but significantly reduced in animal models of heart failure. However, clinical studies have not revealed any changes in distribution profile as well as kinetic and regulatory properties of myocardial PDEs in failing human hearts. A reduction of PDE inhibitors-induced contractile responses in heart failure has therefore been ascribed to reduced cAMP synthesis due to uncoupling of adenylyl cyclase from beta-adrenoreceptor. In cardiac myocytes, PDEs are targeted to distinct subcellular compartments by scaffolding proteins such as myomegalin, mAKAP and beta-arrestins. Over subcellular microdomains, cAMP hydrolysis by PDE3 and PDE4 allows to control the activity of local pools of protein kinase A and therefore the extent of protein kinase A-mediated phosphorylation of cellular proteins.

show abstract

mentioning

confidence: 99%

Myocardial Phosphodiesterases and Regulation of Cardiac Contractility in Health and Cardiac Disease

Osadchii

2007

Cardiovasc Drugs Ther

View full text Add to dashboard Cite

show abstract

“…131 A retrospective analysis of patients receiving milrinone therapy for ADHF showed that more patients could start to receive an ACE inhibitor. 132 However, the study did not report the frequency of symptomatic hypotension. Thirteen percent of patients required dobutamine therapy as a replacement for, or in addition to, milrinone therapy because of hypotension.…”

Section: Transition To Oral Therapymentioning

confidence: 94%

Acute Decompensated Heart Failure: A Contemporary Approach to Pharmacotherapeutic Management

McBride

White

2003

Pharmacotherapy

View full text Add to dashboard Cite

Hospital admissions for acute decompensated heart failure (ADHF) have increased precipitously during the past few decades and are projected to continue to increase in the future. To optimize patient outcomes and reduce the costs associated with this disorder, evidenced-based pharmacotherapy is essential. Continuous infusions of loop diuretic therapy rather than bolus dosing may enhance efficacy and reduce the extent of diuretic resistance. Nesiritide is a pharmacologically novel preload and afterload reducer but based on clinical trial evidence should be reserved for those unable to take or with resistance to intravenous nitrate therapy. Catecholamine- and phosphodiesterase-based inotropic therapies are efficacious, but the increased risk of arrhythmogenesis and the potential for negative survival effects limit their use. The experimental agent levosimendan is a positive inotropic agent but does not increase myocyte calcium concentrations as do catecholamines or phosphodiesterase inhibitors. Clinical trial evidence demonstrates a positive survival benefit for levosimendan versus dobutamine.

show abstract

“…The cellular and molecular mechanisms of β-blockers are not clearly understood but could be related to lowering the heart rate [56] and normalizing adrenergic responsiveness by restoring β-AR density [57], reducing Gi expression [58] and the early transient activation of GRK2 [59]. On the other hand, β-adrenergic agonists, PDE inhibitors and AC agonists can only be used as acute positive inotropic drugs for stabilizing hemodynamics [60]. Administration of PDE inhibitors for a long term in HF patients increases mortality and morbidity [61,62].…”

Section: Sas Signaling In Cardiac Pathophysiologymentioning

confidence: 99%

β-adrenergic System and Cardiac Physiology and Pathophysiology

Liu¹,

Zhang²,

Chen³

2012

Cardiol Pharmacol

View full text Add to dashboard Cite

Tolerability of extended duration intravenous milrinone in patients hospitalized for advanced heart failure and the usefulness of uptitration of oral angiotensin-converting enzyme inhibitors

Cited by 23 publications

References 25 publications

Myocardial Phosphodiesterases and Regulation of Cardiac Contractility in Health and Cardiac Disease

Myocardial Phosphodiesterases and Regulation of Cardiac Contractility in Health and Cardiac Disease

Acute Decompensated Heart Failure: A Contemporary Approach to Pharmacotherapeutic Management

β-adrenergic System and Cardiac Physiology and Pathophysiology

Contact Info

Product

Resources

About