Additive haemodynamic effects of piroximone and prostacyclin in severe chronic heart failure.
This study was undertaken to assess the haemodynamic effects of the combined infusion of prostacyclin and piroximone, a phosphodiesterase inhibitor, in 18 patients with severe congestive heart failure. Right heart catheterization was performed with a Swan-Ganz thermodilution catheter and arterial blood pressure was monitored using a radial line. After baseline haemodynamic measurements, prostacyclin was administered in all patients at the incremental infusion rate of 2, 4, 6 and 8 and 10 ng.kg-1.min-1 during 15 min each. After recovery of baseline haemodynamics, patients were randomly assigned to the piroximone infusion rate of 5 or 10 micrograms.kg-1.min-1 or placebo. After 24 h piroximone or placebo infusion, the same prostacyclin protocol was applied. Prostacyclin infusion added to piroximone resulted in a significant improvement in haemodynamics, as compared to the group receiving prostacyclin added to placebo. As compared to the curve observed with the placebo infusion, 10 ng.kg-1.min-1 prostacyclin infusion resulted in a further increase in cardiac index, by 41 and 38% (P < 0.01) at the piroximone-infusion rates of 5 and 10 micrograms.kg-1.min-1, respectively, whereas systemic vascular resistance decreased by 25 and 21%, respectively (P < 0.01). Additionally, a further decrease in pulmonary capillary wedge pressure by 13 and 11% (P < 0.05) and in pulmonary vascular resistance by 21 and 19% (P < 0.05) was observed at the piroximone-infusion rates of 5 and 10 micrograms.kg-1.min-1, respectively. Consequently, stroke work index increased significantly, as compared to the group receiving prostacyclin added to placebo. This haemodynamic improvement occurred without significant changes in heart rate and mean arterial pressure. Thus, this study shows that in patients with severe congestive heart failure, short-term infusion of prostacyclin is safe and has additive haemodynamic effects on phosphodiesterase inhibitors.
Albo
C
C
Départment de Cardiologie, INSERM U2, Hopital Henri Mondor Créteil, France.
Saal
J P
JP
Lellouche
D
D
Habbal
R
R
Benvenuti
C
C
Deleuze
P
P
Loisance
D
D
Castaigne
A
A
Dubois-Randé
J L
JL
D000328:Adult; D000368:Aged; D002316:Cardiotonic Agents / Q000494:pharmacology*; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D011464:Epoprostenol / Q000494:pharmacology*; D005260:Female; D006321:Heart / Q000502:physiology*; D006333:Heart Failure / Q000188:drug therapy* / Q000503:physiopathology*; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D011652:Pulmonary Circulation / Q000187:drug effects; D014655:Vascular Resistance / Q000187:drug effects
D002316:Cardiotonic Agents; D007093:Imidazoles; C039686:piroximone; D011464:Epoprostenol