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Milrinone improves diastolic function in coronary artery bypass surgery as assessed by acoustic quantification and peak filling rate: a prospective randomized study
Dept of Cardiothoracic Surgery and Anestesiology, Örebro University hospital.
Dept of Cardiothoracic Surgery and Anestesiology, Örebro University hospital.
Statistical and Epidemiological Unit, Örebro University hospital.
Thoracic clinic, Karolinska University hospital.
2010 (English)In: Journal of Cardiothoracic and Vascular Anesthesia, ISSN 1053-0770, E-ISSN 1532-8422, Vol. 24, no 2, 244-249 p.Article in journal (Refereed) Published
Abstract [en]

OBJECTIVE: To compare the effects of a bolus dose of milrinone, 50 microg/kg, to placebo on diastolic function (active relaxation) in patients undergoing on-pump coronary artery bypass grafting (CABG).

DESIGN: Prospective, randomized, double-blind, placebo-controlled study.

SETTING: University hospital.

PARTICIPANTS: Twenty-four patients with stable angina and left ventricular ejection fraction >30%, scheduled for elective CABG using cardiopulmonary bypass (CPB), were included.

INTERVENTION: Patients were randomized to receive either 50 microg/kg of milrinone (n = 12) or placebo (n = 12) after aortic declamping.

MEASUREMENTS AND MAIN RESULTS: The diastolic function of the left ventricle (LV) was measured as peak filling rate (dA/dt [maximal diastolic area change over time]) with transesophageal echocardiography (TEE) using acoustic quantification (AQ) before CPB and 10 minutes after termination of CPB. The normalized peak filling rate (dA/dt)/EDA was also calculated. Active relaxation was statistically significantly increased in the milrinone group compared with the placebo group after CPB.

CONCLUSION: Patients undergoing CABG surgery and treated with milrinone after aortic declamping had better diastolic function following cardiopulmonary bypass.

Place, publisher, year, edition, pages
2010. Vol. 24, no 2, 244-249 p.
National Category
Anesthesiology and Intensive Care
URN: urn:nbn:se:umu:diva-68815DOI: 10.1053/j.jvca.2009.10.007PubMedID: 20022262OAI: diva2:618001
Available from: 2013-04-25 Created: 2013-04-25 Last updated: 2013-05-03Bibliographically approved
In thesis
1. Cardiac effects of non-adrenergic inotropic drugs: clinical and experimental studies
Open this publication in new window or tab >>Cardiac effects of non-adrenergic inotropic drugs: clinical and experimental studies
2013 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Background: Myocardial failure and dysfunction is not uncommon during critical illness and following cardiac surgery. For optimal treatment, a better understanding of the effects of inotropic drugs is needed. In this thesis, two non-adrenergic mediated inotropes, milrinone and levosimendan were studied in different models of myocardial dysfunction. The study aims were to assess the following: the effects of milrinone on blood flow in coronary artery bypass grafts during CABG surgery; the effects of milrinone on left ventricular diastolic function during post-ischaemic myocardial dysfunction; whether milrinone or levosimendan are protective or injurious during acute myocardial ischaemia, and if levosimendan potentiates myocardial function when added to milrinone in an experimental model of post-ischaemic (stunned) myocardium.

Material and Methods: In Study I, 44 patients undergoing coronary artery bypass surgery(CABG) were included as subjects. Milrinone or saline was administrated in a single dose during cardio-pulmonary bypass (CPB) and coronary graft flow measurements were recorded after 10 and 30 min following CPB. In Study II; 24 patients undergoing CABG had estimations of peak ventricular filling rates made before and after CPB with administration of milrinone or saline as a single dose during CPB, performed by assessment of the rate of change in diastolic cross-sectional left ventricular area. In Study III, energy-metabolic effects of milrinone and levosimendan were measured in an anaesthetized porcine model during 45 minutes of regional myocardial ischemia. Microdialysis sampling of metabolites of local ischemic metabolism allowed assessment of glycolytic activity and the degree of myocardial calcium overload. In Study IV, in a porcine model of postischaemic myocardial stunning, ventricular pressure-volume relationships were analyzed when milrinone or a combination of milrinone and levosimendan were given together.

Results: In Study I, there was a clear increase in non-sequential saphenous vein graft blood flow with milrinone at 10 minutes (64.5 ± 37.4 compared to placebo 43.6 ± 25.7 ml/min (mean ± SD).). A decreasing but still measureable flow increase was seen for milrinone at 30 minutes. In Study II, an increase in early left ventricular filling rate (ventricular cross-sectional area rate of change,dA/dt) was seen in the milrinone treated group. Pre-bypass milrinone group dA/dt 22.0 ± 9.5 changed to post-bypass values dA/dt 27.8 ± 11.5 cm2/sec). Placebo group pre-bypass dA/dt was 21.0 ± 8.7 and post-bypass 17.1 ± 7.1 cm2/sec. A milrinone effect was demonstrated in an adjusted regression model (p = 0.001). In Study III, neither milrinone nor levosimendan led to a change in energy-metabolic activity during ischemia as reflected by interstitial glucose, pyruvate, lactate orglycerol. Neither drug exacerbated the relative myocardial calcium overload during ischemia. In Study IV, milrinone improved active relaxation (tau) in post-ischemic stunned myocardium, but did not markedly improve systolic function by preload recruitable stroke work. Levosimendan added to milrinone showed minimal effect on active relaxation but a positive effect on systolic function in combination with milrinone.

Conclusions: We conclude that milrinone treatment leads to an increase in blood flow in newly implanted coronary saphenous vein grafts, and improves ventricular relaxation post-cardiopulmonary bypass. Neither milrinone nor levosimendan, in this porcine model, negatively influence myocardial energy metabolism or calcium overload during acute ischaemia. Addition of levosimendan to milrinone treatment during post-ischaemic ventricular dysfunction may provide additive inotropic effects on systolic function but probably not for active relaxation.

Place, publisher, year, edition, pages
Umeå: Umeå Universitet, 2013. 93 p.
Umeå University medical dissertations, ISSN 0346-6612 ; 1568
Milrinone, levosimendan, vein graft flow, myocardial ischemia, protection, inotropy, diastole
National Category
Anesthesiology and Intensive Care
Research subject
urn:nbn:se:umu:diva-68967 (URN)978-91-7459-610-6 (ISBN)
Public defence
2013-05-30, Wilandersalen, Universitetssjukhuset, Örebro, Örebro, 13:00 (Swedish)
Available from: 2013-05-03 Created: 2013-05-02 Last updated: 2013-05-06Bibliographically approved

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