Olprinone, a phosphodiesterase III inhibitor, reduces gut mucosal injury and portal endotoxin level during acute hypoxia in rabbits.
BACKGROUND
Preservation of gut integrity has become a therapeutic goal to obviate bacterial translocation in the critically ill. The authors examined whether olprinone, a phosphodiesterase III inhibitor, protected functional and structural integrity of gut mucosa against acute progressive hypoxia.


METHODS
Thirty-two animals were randomly allocated to a control group (n = 12), a low-dose group (0.2 microg x kg-1 x min-1 olprinone; n = 10), or a high-dose group (0.6 microg x kg-1 x min-1 olprinone; n = 10) after preparatory surgery. Ascending aortic and portal blood flow, intramural pH of the ileum, and portal endotoxin levels were measured at normoxia and through three stages of progressive hypoxia (fraction of inspired oxygen = 0.17, 0.13, and 0.10).


RESULTS
At normoxia, ascending aortic flow in the high-dose group was approximately 20% higher than in the control and low-dose groups. During progressive hypoxia, both ascending aortic and portal flow in the control group were depressed, whereas olprinone infusion attenuated such alterations and redistributed blood to the splanchnic area in a dose-dependent manner. On the contrary, the reduction of intramural pH of the ileum and the elevation of portal endotoxin levels observed in the control group were significantly minimized in both the low- and high-dose groups to a similar extent during acute hypoxia. Histopathologic alterations of gut mucosa observed in the control group were minimized by olprinone infusion dose-independently, accompanied by reduction of mortality rate of the animals.


CONCLUSIONS
Olprinone slows progression of intestinal mucosal acidosis and gut barrier dysfunction, concurrently with preservation of microscopic structures, through both flow-dependent and -independent mechanisms under acute hypoxia. Such properties of olprinone may serve to protect the host under insult.
Satoh
Tomoyuki
T
Department of Anesthesiology and General Intensive Care Unit, Keio University School of Medicine, Tokyo, Japan.
Morisaki
Hiroshi
H
Ai
Kimiaki
K
Kosugi
Shizuko
S
Yamamoto
Michiko
M
Serita
Ryohei
R
Kotake
Yoshifumi
Y
Takeda
Junzo
J
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000378:metabolism*; D000208:Acute Disease; D000818:Animals; D002245:Carbon Dioxide / Q000378:metabolism; D054684:Cyclic Nucleotide Phosphodiesterases, Type 3; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D004731:Endotoxins / Q000097:blood*; D006863:Hydrogen-Ion Concentration; D000860:Hypoxia / Q000378:metabolism*; D007093:Imidazoles / Q000627:therapeutic use*; D007413:Intestinal Mucosa / Q000187:drug effects / Q000473:pathology*; D008297:Male; D009929:Organ Size / Q000187:drug effects / Q000502:physiology; D010101:Oxygen Consumption / Q000187:drug effects / Q000502:physiology; D010726:Phosphodiesterase Inhibitors / Q000627:therapeutic use*; D011169:Portal Vein / Q000378:metabolism; D011728:Pyridones / Q000627:therapeutic use*; D011817:Rabbits; D013152:Splanchnic Circulation / Q000187:drug effects
D004731:Endotoxins; D007093:Imidazoles; D010726:Phosphodiesterase Inhibitors; D011728:Pyridones; D002245:Carbon Dioxide; C059498:olprinone; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D054684:Cyclic Nucleotide Phosphodiesterases, Type 3