Cardiac effects of non-adrenergic inotropic drugs

Cover illustration " Weighing of the Heart " from chapter 125 of " the Book of the Dead " , a famous papyrus from the 19th Dynasty of the New Kingdom in ancient Egypt, dated around 1250 BC. Second thoughts Tage Danielsson from " Thoughts from the root " (1974) I believe in doubt. Doubt is the basis of all knowledge and the engine of all change. Doubt is, to make doubly sure, the prerequisite of faith. He who believes without first doubting is an exulting blockhead and a tinkling cymbal. And he who believes without at the same time doubting is hardly less of an exulting blockhead and hardly less of a tinkling cymbal. Faith can remove mountains but doubt can put them back in place again. Reprinted with permission from the copyright holder I wish to dedicate this book to my family. Abstract 4 Abstract 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 administered 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 in 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 …