Influence of ischaemic cardioplegic arrest on the haemodynamic efficacy of the PDE-III inhibitor, enoximone.
The haemodynamic support from an enoximone infusion (2 x bolus 0.5 mg.kg-1, infusion 0.5 micrograms.kg-1min-1) in the early postischaemic phase is modified by a transient diminution of the drug's positive inotropic and vasodilatory effect (1 to 4 h). Forty-five min after weaning off cardiopulmonary bypass (CPB) the initial increase in cardiac index (CI) induced by enoximone (+26 +/- 8%) faded and was no longer discernible in the control group. A significant increase in CI was observed again 4-6 h after cardioplegic arrest (ultimate steady state values greater than 10 h; CI +0.71.min-1 x m-2; +21%). This pharmacodynamic fading occurred in the presence of constant plasma concentrations of enoximone (442 +/- 31 ng.ml-1) and elevated high plasma norepinephrine (926 +/- 70 pg.ml-1). Two independent processes might be responsible for the ischaemia-induced complex time dependency of the pharmacodynamic effect: (1) sensitization of the adrenergic receptor pathway and/or activation of sarcolemmal Ca-influx, rapidly reversed during reperfusion, and (2) impaired sarcoplasmic reticulum responses, which are slowly repaired after weaning off CPB.
Preuner
J G
JG
Dept. of Cardiovascular Surgery, Rehabilitationszentrum, Krozingen, Germany.
Gieseke
R
R
Kasper
W
W
Birnbaum
D
D
D002302:Cardiac Output / Q000187:drug effects*; D002315:Cardiopulmonary Bypass; D002316:Cardiotonic Agents / Q000494:pharmacology*; D017335:Enoximone; D005260:Female; D006324:Heart Arrest, Induced; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D013997:Time Factors
D002316:Cardiotonic Agents; D007093:Imidazoles; D017335:Enoximone