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milrinone
Milrinone, commonly known and marketed under the brand name Primacor, is a medication used in patients who have heart failure. It is a phosphodiesterase 3 inhibitor that works to increase the heart's contractility and decrease pulmonary vascular resistance. Milrinone also works to vasodilate which helps alleviate increased pressures (afterload) on the heart, thus improving its pumping action. While it has been used in people with heart failure for many years, recent studies suggest that milrinone may exhibit some negative side effects that have caused some debate about its use clinically.〔Packer, M. Calcium channel blockers in chronic heart failure: The risks of ‘ physiologically rational ’ therapy () . C irculation 8 2,
2254 – 2257.〕〔Packer M, Carver J, Rodeheffer R, Ivanhoe R, DiBianco R, Zeldis S et al. Effect of Oral Milrinone on Mortality in Severe Chronic Heart Failure. The New England Journal of Medicine. 21 Nov 1991;325(21):1468-1475.〕
Overall, milrinone supports ventricular functioning of the heart by decreasing the degradation of cAMP and thus increasing phosphorylation levels of many components in the heart that contribute to contractility and heart rate. Milrinone use following cardiac surgery has been under some debate because of the potential increase risk of postoperative atrial arrhythmias.〔Fleming G, Murray K, Yu C, Byrne J, Greelish J, Petracek M et al. Milrinone Use Is Associated With Postoperative Atrial Fibrillation After Cardiac Surgery. The Journal of the American Heart Association. 29 Sept 2008;118:1619-1625.〕 However, in the short term milrinone has been deemed beneficial to those experiencing heart failure and an effective therapy to maintain heart function following cardiac surgeries. There is no evidence of any long term beneficial effects on survival.〔British National Formulary. 66 ed. London: BMJ Group and Pharmaceutical Press; Sept 2013〕
==Contractility in the heart==
People experiencing heart failure have a significant decrease in the contractile ability of heart cells (cardiomyocytes). This impaired contractility occurs through a number of mechanisms. Some of the main problems associated with decreased contractility in those with heart failure are issues arising from imbalances in the concentration of calcium. Calcium permits myosin and actin to interact which allows initiation of contraction within the cardiomyocytes. In those with heart failure there may be a decreased amount of calcium within the cardiomyocytes reducing the available calcium to initiate contraction. When contractility is decreased the amount of blood being pumped out of the heart into circulation is decreased as well. This reduction in cardiac output causes many systemic implications such as fatigue, syncope and other issues associated with decreased blood flow to peripheral tissues.
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