Inhibition of phosphodiesterase type III before aortic cross-clamping preserves intramyocardial cyclic adenosine monophosphate during cardiopulmonary bypass.
Inotropes are often used to treat myocardial dysfunction shortly after cardiopulmonary bypass (CPB). beta-Adrenergic agonists improve contractility, in part by increasing cyclic adenosine monophosphate (cAMP) production, whereas phosphodiesterase type III inhibitors prevent its breakdown. CPB is associated with abnormalities at the beta-receptor level and diminished adenyl cyclase activity, both of which tend to decrease cAMP. These effects may be increased in the presence of preexisting myocardial dysfunction. We tested the hypothesis that inhibition of phosphodiesterase type III before global myocardial ischemia and pharmacologic arrest results in the preservation of intramyocardial cAMP concentration during CPB. Twenty adult patients undergoing coronary artery bypass grafting with CPB were studied. After CPB was instituted, a myocardial biopsy was obtained from the apex of the left ventricle. Patients were randomized to receive either placebo or milrinone (50 micro/kg) through the bypass pump 10 min before aortic cross-clamping. Another myocardial biopsy was performed adjacent to the left ventricular apex just before weaning from CPB. Myocardial cAMP concentration was determined by radioimmunoassay. Myocyte protein content was determined by the Bradford method by using a commercial kit. There were no significant demographic differences between the groups; however, patients in the Milrinone group had a lower left ventricular ejection fraction than placebo (41% +/- 13% vs 53% +/- 7%; P < 0.05). Patients who received milrinone had larger cAMP concentrations at the end of CPB compared with placebo (21 +/- 12.5 pmol/mg protein versus 12.8 +/- 2.2 pmol/mg protein; P < 0.05). The administration of milrinone before aortic cross-clamping is associated with increased intramyocardial cAMP concentration at the end of CPB.


CONCLUSIONS
The administration of a single dose of milrinone before aortic cross-clamping resulted in significantly larger intramyocardial cyclic adenosine monophosphate concentration in myocardial biopsy specimens compared with controls.
Janelle
G M
GM
Department of Anesthesiology, University of Florida College of Medicine, Gainesville, 32610, USA.
Urdaneta
F
F
Blas
M L
ML
Shryock
J
J
Tang
Y S
YS
Martin
T D
TD
Lobato
E B
EB
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors*; D000368:Aged; D001011:Aorta / Q000502:physiology; D002315:Cardiopulmonary Bypass / Q000009:adverse effects*; D003250:Constriction; D000242:Cyclic AMP / Q000378:metabolism*; D054684:Cyclic Nucleotide Phosphodiesterases, Type 3; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D007036:Hypothermia, Induced; D007432:Intraoperative Period; D008297:Male; D008875:Middle Aged; D020105:Milrinone / Q000627:therapeutic use*; D009206:Myocardium / Q000378:metabolism*; D010726:Phosphodiesterase Inhibitors / Q000627:therapeutic use*
D010726:Phosphodiesterase Inhibitors; D000242:Cyclic AMP; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D054684:Cyclic Nucleotide Phosphodiesterases, Type 3; D020105:Milrinone