Effects of phosphodiesterase III inhibition on length-dependent regulation of myocardial function in coronary surgery patients.
BACKGROUND
Phosphodiesterase III inhibitors increase myocardial contractility and decrease left ventricular (LV) afterload. We studied whether these effects altered LV response to an increase in cardiac load and affected length-dependent regulation of myocardial function.


METHODS
Before the start of cardiopulmonary bypass, a high-fidelity pressure catheter was positioned in the left ventricle and the left atrium in 10 coronary surgery patients. LV response to an increased cardiac load, caused by leg elevation, was assessed during baseline conditions and after administration of milrinone at a dose of 20 micrograms kg-1 over 15 min. Effects on contraction were measured by changes in maximal rate of pressure development (dP/dtmax). Effects on relaxation were assessed by analysis of changes in maximum rate of pressure decrease and by analysis of the load dependency of myocardial relaxation (R = slope of the relation between the time constant of isovolumic relaxation and end systolic pressure).


RESULTS
Milrinone increased dP/dtmax but measures of relaxation were unaltered. Leg elevation had more effect on measures of contraction and relaxation after milrinone than at baseline. The relationship between R and changes in dP/dtmax shifted downwards and to the right with milrinone, whereas the relationship between R and changes in end diastolic pressure (EDP) shifted downwards and to the left.


CONCLUSIONS
This suggests that milrinone improved contraction, reduced the load dependency of LV pressure decrease, and reduced the change in EDP after leg elevation.
De Hert
S G
SG
Department of Anaesthesiology, University Hospital Antwerp, Wilrijkstraat 10, B-2650 Edegem, Belgium.
ten Broecke
P W
PW
Mertens
E
E
Rodrigus
I E
IE
Stockman
B A
BA
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors; D000368:Aged; D002316:Cardiotonic Agents / Q000494:pharmacology*; D001026:Coronary Artery Bypass; D054684:Cyclic Nucleotide Phosphodiesterases, Type 3; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D020105:Milrinone / Q000494:pharmacology*; D009200:Myocardial Contraction / Q000187:drug effects*; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D016277:Ventricular Function, Left / Q000187:drug effects
D002316:Cardiotonic Agents; D010726:Phosphodiesterase Inhibitors; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D054684:Cyclic Nucleotide Phosphodiesterases, Type 3; D020105:Milrinone