Effects of olprinone, a new phosphodiesterase inhibitor, on gastric intramucosal acidosis and systemic inflammatory responses following hypothermic cardiopulmonary bypass.
BACKGROUND
Phosphodiesterase (PDE) III inhibitors have both an inotropic and a peripheral vasodilatory effect, and also inhibit the activation of macrophages. Thus a newly developed PDE III inhibitor, olprinone, could modify gastric intramucosal pH (pHi), systemic oxygen consumption, and systemic inflammatory responses in patients undergoing cardiac surgery with cardiopulmonary bypass (CPB).


METHODS
We studied 23 patients. In 15 patients, olprinone (0.1 or 0.2 microg x kg(-1) x min(-1)) was administered from the commencement of CPB until their admission to the ICU. The other 8 patients received placebo. The pHi and regional CO2 tension (PrCO2) were assessed by a capnometric air tonometry. Systemic inflammatory responses were evaluated by serum interleukin-6 (IL-6), IL-10, and leucocyte counts.


RESULTS
The pHi and PCO2-gap, the difference between PrCO2 and arterial CO2 tension (PaCO2), showed a transient decrease and an increase after CPB, respectively. Although olprinone did not affect pHi, olprinone at 0.2 microg x kg(-1) x min(-1) significantly lessened post-CPB increase in PCO2-gap. Olprinone at 0.2 microg x kg(-1) x min(-1) significantly increased IL-10 and reduced the extent of leucocytosis, while it did not affect IL-6 levels. At the same dosage, olprinone also lessened the surge in systemic oxygen uptake index (VO2) and augmented the increase in mixed oxygen saturation (SvO2) both of which occurred after CPB. At 0.1 microg x kg(-1) x min(-1), however, olprinone did not show any significant effect.


CONCLUSIONS
Our results suggest that olprinone at 0.2 microg x kg(-1) x min(-1) suppresses gastric intramucosal acidosis and systemic inflammation following CPB.
Yamaura
K
K
Department of Anaesthesiology and Critical Care Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Akiyoshi
K
K
Irita
K
K
Taniyama
T
T
Takahashi
S
S
D000138:Acidosis / Q000188:drug therapy* / Q000209:etiology; D000368:Aged; D002315:Cardiopulmonary Bypass / Q000009:adverse effects*; D005260:Female; D005745:Gastric Acidity Determination; D005753:Gastric Mucosa / Q000187:drug effects*; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D007036:Hypothermia, Induced / Q000009:adverse effects*; D007093:Imidazoles / Q000627:therapeutic use*; D007249:Inflammation / Q000188:drug therapy* / Q000209:etiology; D016753:Interleukin-10 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010092:Oximetry; D010726:Phosphodiesterase Inhibitors / Q000627:therapeutic use*; D011728:Pyridones / Q000627:therapeutic use*; D014065:Tonometry, Ocular
D007093:Imidazoles; D015850:Interleukin-6; D010726:Phosphodiesterase Inhibitors; D011728:Pyridones; D016753:Interleukin-10; C059498:olprinone