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Advanced Therapeutic Options in Acute Heart Failure
Published in Andreas P. Kalogeropoulos, Hal A. Skopicki, Javed Butler, Heart Failure, 2023
Tiffany Dong, Aditi Nayak, Alanna Morris
Milrinone inhibits phosphodiesterase 3, ultimately preventing breakdown of cyclic adenosine monophosphate (cAMP). This increases myocardial inotropy and diastolic compliance, while reducing systemic and pulmonary vascular resistance, and thus improves cardiac index, filling pressures, and afterload.21 Milrinone can also be used for right ventricular (RV) failure.22 Doses range from 0.125 to 0.75 mcg/kg/min. There is a synergistic effect with dobutamine as both increase cAMP. Compared with dobutamine, milrinone may be appropriate in patients who have downregulation of their adrenergic receptors. Side effects include hypotension, cardiac ischemia due to increased myocardial demand, and arrhythmias. Caution should be used in patients with renal dysfunction, as milrinone is renally cleared.3
Cardiovascular, Hemodynamic, and Critical Care Considerations in the Patient With Necrotizing Enterocolitis
Published in David J. Hackam, Necrotizing Enterocolitis, 2021
Christine C. Pazandak, Zachary A. Vesoulis, Misty Good
Milrinone is a phosphodiesterase type 3 inhibitor that leads to an accumulation of cyclic adenosine monophosphate (cAMP) (15, 44). The increased concentration of cAMP in the myocyte facilitates the influx of calcium in the cell, causing increased myocardial contractility (15). Similar increases of calcium in smooth muscle cells cause relaxation allowing for vasodilation (15). Unlike other inotropes, milrinone also promotes myocardial relaxation via breakdown of the actin–myosin complex (15). There are very limited data on the use of milrinone in preterm infants, with a single double-blind randomized placebo-controlled trial (45). This study evaluated the prophylactic use of milrinone to improve superior vena cava (SVC) flow in the first 24 hours of life (45). Despite the theoretical advantages of milrinone, given its mechanism of action and the characteristics of immature myocardium, this study found no benefit in preterm infants from the early use of milrinone (45). The authors presented many limitations of the study, which included preceding parenteral volume load, prophylactic indomethacin administration, and low incidence of decreased SVC flow (45). Additional studies are required before milrinone can be recommended for widespread use in the preterm population (45).
Thromboembolism and Amniotic Fluid Embolism
Published in Afshan B. Hameed, Diana S. Wolfe, Cardio-Obstetrics, 2020
The harbinger of treatment of cardiovascular collapse relies on urgent, immediate delivery in the setting of current pregnancy and high-quality cardiopulmonary resuscitation per ACLS guidelines [35]. When return of spontaneous circulation (ROSC) is achieved, the cardiovascular system must be maintained. Resuscitative efforts are multidisciplinary and employ maternal-fetal medicine, intensive care, cardiac surgery, and pulmonary medicine. In the setting of acute right-sided failure, inotropic support with milrinone and dobutamine may be of great use. Both agents aid in right-sided cardiac contractility, and also milrinone has pulmonary artery vasodilatory effects which allows further optimization of preload in biventricular failure resulting in an increased cardiac output [37,38]. However, care must be taken with these medications because they can be arrhythmogenic and cause systemic hypotension, which is undesirable with the combined distributive shock of an AFE.
An update of cyclic nucleotide phosphodiesterase as a target for cardiac diseases
Published in Expert Opinion on Drug Discovery, 2021
rate and magnitude of cardiac contractility, which is the basis for using PDE3 inhibitors to treat congestive heart failure. Also, PDE3 inhibition stimulates vascular relaxation, thus reducing peripheral and pulmonary vascular resistance and enhances coronary blood flow. Thus, PDE3 inhibitors such as milrinone have become powerful drugs for the short-term treatment of life-threatening heart failure due to their inotropic and vasodilatory actions. Several PDE3 inhibitors are currently FDA approved and marketed inside or outside the USA. Milrinone is FDA-approved in 1987 for the treatment of acute HF or chronic HF [135,136]. Milrinone markedly improves cardiac performances including increasing cardiac contractility, cardiac relaxation, and vasodilation [136]. Concerns about its adverse effects, such as an increased risk of supraventricular and ventricular arrhythmias, and hypotension, make Milrinone to be used with special cautions [135,137]. There are continued interests and efforts in optimizing the therapeutic regiment for using PDE3 inhibitors in treating heart failure. For example, a phase II clinical trial is ongoing to test a hypothesis that carefully monitoring and optimizing Milrinone levels in children following cardiac surgery may improve clinical outcomes and reduce the duration of Milrinone infusion (ClinicalTrials.gov Identifier: NCT01841177).
Investigation of the Effect of Milrinone on Renal Damage in an Experimental Non-Heart Beating Donor Model
Published in Journal of Investigative Surgery, 2018
Erdal Uysal, Mehmet Dokur, Serdar Altınay, Eyup İlker Saygılı, Kadir Batcıoglu, Mehmet S. Ceylan, Hatem Kazımoglu, Burcin A. Uyumlu, Mehmet Karadag
Milrinone is a phosphodiesterase 3 inhibitor used in the treatment of congestive heart failure. Milrinone increases intracellular c-AMP concentration. It provides vasodilation in the arteries and venules [35]. It increases blood flow in the tissue and suppresses TNF-alpha production. Increased TNF-alpha release leads to tissue damage by increasing production of eicosanoid analogs and free oxygen radicals [6]. TNF-alpha facilitates coagulation by increasing the production of vasopressor agents such as platelet-activating factor and endothelin-1. Thus, microcirculation deteriorates and tissue blood flow decreases [7]. Tubular obstruction and acute tubular necrosis occur due to increased vasoconstriction [36]. Therefore, suppression of TNF-alpha plays a key role in preventing ischemia-reperfusion injury. Previous studies have shown the efficacy of TNF-alpha inhibitors in preventing ischemia-reperfusion injury [37]. Milrinone is thought to be effective in ischemia reperfusion injury because it is an agent that inhibits TNF-alpha. Milrinone has been shown to reduce ischemic reperfusion injury in the lung, liver, heart and rat kidneys [11, 16, 17]. However, it is predicted that it can also reduce renal failure in the experimental non -heart beating donor model in which the renal arterial and venous blood flow is completely eliminated and does not provide blood flow again.
Managing respiratory complications in infants and newborns with congenital diaphragmatic hernia
Published in Expert Opinion on Orphan Drugs, 2020
Sandeep Shetty, Fahad M. S. Arattu Thodika, Anne Greenough
Delivery of infants with CDH is recommended close to term. Studies in lambs suggest that physiological/delayed cord clamping reduces pulmonary vascular resistance and significantly increases pulmonary blood flow in those with CDH [66]. Delayed cord clamping is being investigated in a trial for infants born with CDH (NCT03314233). Gentle ventilation in the delivery suite may reduce morbidity and routine administration of a neuromuscular blocking agent should be avoided. On the neonatal unit, conventional mechanical ventilation should be used and diaphragmatic closure attempted only when the infant’s condition has stabilized. Current postnatal protocols regarding treating pulmonary hypertension in infants with CDH are mostly based on trials performed in infants with other causes of pulmonary hypertension [171]. The treatment of pulmonary hypertension remains controversial and randomized trials are required to decide optimum management. Echocardiography is critical for characterizing the severity of pulmonary hypertension and myocardial function and allows for targeted identification of systemic therapies that optimize hemodynamic function or reduce pulmonary vascular resistance. Emerging evidence suggests that cardiac dysfunction may be a cause of impending irreversible cardiopulmonary failure, more than the severity of PPHN [172–174]. The role of milrinone is currently being evaluated in a randomized trial in participating centers of the neonatal research network [175]. A European multicentre randomized controlled trial is comparing the efficacy of intravenous sildenafil and inhaled nitric oxide and incorporating cardiac function assessment (CoDiNOS trial) [96].