Hemodynamic effects of the novel selective cAMP-phosphodiesterase III inhibitor R 80122 in anesthetized patients with moderate left ventricular dysfunction before coronary artery bypass grafting.
OBJECTIVE
To investigate the hemodynamic effects and safety of R 80122, a novel selective phosphodiesterase (PDE) III inhibitor, and its solvent hydroxypropyl-beta-cyclodextrin.


METHODS
Prospective, randomized study.


METHODS
Operating theater of a university hospital in the Netherlands.


METHODS
Twelve patients with impaired left ventricular function scheduled for coronary artery bypass grafting after induction of anesthesia were included.


METHODS
R 80122 (n = 6) or its solvent (n = 6) was administered using the same infusion regimen. A bolus of 0.1 mL/kg (= 0.1 mg/kg R 80122) was infused over 10 minutes followed by a maintenance infusion of 5 microliters/kg/min (5 micrograms/kg/min R 80122) over 20 minutes.


RESULTS
Compared with the solvent, patients receiving R 80122 did not show any significant changes in heart rate, arterial blood pressure, or pulmonary artery pressures. However, R 80122 produced a marked increase (P < 0.05) in cardiac output (thermodilution) and echocardiographically obtained percentage area reduction. No arrhythmias or ischemic episodes occurred during the infusion period. The plasma half-life of R 80122 was 10.6 +/- 1.9 minutes.


CONCLUSIONS
R 80122 appears to be a potent positive inotropic agent in these patients. Its use is not associated with marked vasodilation, it is devoid of positive chronotropic effects, and it can be administered safely in patients with impaired left ventricular function.
Vroom
M B
MB
Department of Anesthesiology, Free University Amsterdam, The Netherlands.
van Wezel
H B
HB
Visser
C A
CA
Eijsman
L
L
van Zwieten
P A
PA
D000073738:2-Hydroxypropyl-beta-cyclodextrin; D000368:Aged; D000768:Anesthesia, General; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D002316:Cardiotonic Agents / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use*; D001026:Coronary Artery Bypass; D003505:Cyclodextrins / Q000008:administration & dosage / Q000494:pharmacology; D017548:Echocardiography, Transesophageal; D005260:Female; D006207:Half-Life; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use*; D007262:Infusions, Intravenous; D008297:Male; D010726:Phosphodiesterase Inhibitors / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use*; D011292:Premedication; D011446:Prospective Studies; D011669:Pulmonary Wedge Pressure / Q000187:drug effects; D011799:Quinazolines / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use*; D012449:Safety; D012997:Solvents / Q000008:administration & dosage / Q000494:pharmacology; D018487:Ventricular Dysfunction, Left / Q000517:prevention & control*; D047392:beta-Cyclodextrins
D002316:Cardiotonic Agents; D003505:Cyclodextrins; D007093:Imidazoles; D010726:Phosphodiesterase Inhibitors; D011799:Quinazolines; D012997:Solvents; D047392:beta-Cyclodextrins; C076518:R 80122; D000073738:2-Hydroxypropyl-beta-cyclodextrin