Inhibition of phosphodiesterase type III before aortic cross-clamping preserves intramyocardial cyclic adenosine monophosphate during cardiopulmonarybypass
Gm. Janelle et al., Inhibition of phosphodiesterase type III before aortic cross-clamping preserves intramyocardial cyclic adenosine monophosphate during cardiopulmonarybypass, ANESTH ANAL, 92(6), 2001, pp. 1377-1383
Citations number
49
Categorie Soggetti
Aneshtesia & Intensive Care","Medical Research Diagnosis & Treatment
Inotropes are of ten used to treat myocardial dysfunction shortly after car
diopulmonary bypass (CPB). beta -Adrenergic agonists improve contractility,
in part by increasing cyclic adenosine monophosphate (cAMP) production whe
reas phosphodiesterase type III inhibitors prevent its breakdown. CPB is as
sociated with abnormalities at the beta -receptor level and diminished aden
yl cyclase activity, both. of which tend to decrease cAMP. These effects ma
y be increased in the presence of preexisting myocardial dysfunction. We te
sted the hypothesis that inhibition of phosphodiesterase type m before glob
al myocardial ischemia and pharmacologic arrest results in the preservation
of intramyocardial cAMP concentration during CPB. Twenty adult patients un
dergoing coronary artery bypass grafting with CPB were studied. After CPB w
as instituted, a myocardial biopsy was obtained from the apex of the left v
entricle. Patients were randomized to receive either placebo or milrinone (
50 mug/kg) through the bypass pump 10 min before aortic cross-clamping. Ano
ther 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 di
fferences 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 cAMT concent
rations at the end of CPB compared with placebo (21 +/- 12.5 pmol/mg protei
n versus 12.8 +/- 2.2 pmol/mg protein; P < 0.05). The administration of mil
rinone before aortic cross-clamping is associated with increased intramyoca
rdial cAMP concentration at the end of CPB.