Olprinone, a phosphodiesterase III inhibitor, reduces gut mucosal injury and portal endotoxin level during acute hypoxia in rabbits

Tomoyuki Satoh, Hiroshi Morisaki, Kimiaki Ai, Shizuko Kosugi, Michiko Yamamoto, Ryohei Serita, Yoshifumi Kotake, Junzo Takeda

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

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 μg · kg-1 · min-1 olprinone; n = 10), or a high-dose group (0.6 μg · kg-1 · 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.

Original languageEnglish
Pages (from-to)1407-1414
Number of pages8
JournalAnesthesiology
Volume98
Issue number6
DOIs
Publication statusPublished - 2003 Jun 1

Fingerprint

Type 3 Cyclic Nucleotide Phosphodiesterases
Phosphodiesterase Inhibitors
Endotoxins
Rabbits
Wounds and Injuries
Control Groups
Ileum
Mucous Membrane
Bacterial Translocation
Viscera
Acidosis
olprinone
Hypoxia
Critical Illness
Oxygen
Mortality

ASJC Scopus subject areas

  • Anesthesiology and Pain Medicine

Cite this

Olprinone, a phosphodiesterase III inhibitor, reduces gut mucosal injury and portal endotoxin level during acute hypoxia in rabbits. / Satoh, Tomoyuki; Morisaki, Hiroshi; Ai, Kimiaki; Kosugi, Shizuko; Yamamoto, Michiko; Serita, Ryohei; Kotake, Yoshifumi; Takeda, Junzo.

In: Anesthesiology, Vol. 98, No. 6, 01.06.2003, p. 1407-1414.

Research output: Contribution to journalArticle

Satoh, Tomoyuki ; Morisaki, Hiroshi ; Ai, Kimiaki ; Kosugi, Shizuko ; Yamamoto, Michiko ; Serita, Ryohei ; Kotake, Yoshifumi ; Takeda, Junzo. / Olprinone, a phosphodiesterase III inhibitor, reduces gut mucosal injury and portal endotoxin level during acute hypoxia in rabbits. In: Anesthesiology. 2003 ; Vol. 98, No. 6. pp. 1407-1414.
@article{8b329dbf85264069baf5644b4c5d1142,
title = "Olprinone, a phosphodiesterase III inhibitor, reduces gut mucosal injury and portal endotoxin level during acute hypoxia in rabbits",
abstract = "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 μg · kg-1 · min-1 olprinone; n = 10), or a high-dose group (0.6 μg · kg-1 · 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.",
author = "Tomoyuki Satoh and Hiroshi Morisaki and Kimiaki Ai and Shizuko Kosugi and Michiko Yamamoto and Ryohei Serita and Yoshifumi Kotake and Junzo Takeda",
year = "2003",
month = "6",
day = "1",
doi = "10.1097/00000542-200306000-00016",
language = "English",
volume = "98",
pages = "1407--1414",
journal = "Anesthesiology",
issn = "0003-3022",
publisher = "Lippincott Williams and Wilkins",
number = "6",

}

TY - JOUR

T1 - Olprinone, a phosphodiesterase III inhibitor, reduces gut mucosal injury and portal endotoxin level during acute hypoxia in rabbits

AU - Satoh, Tomoyuki

AU - Morisaki, Hiroshi

AU - Ai, Kimiaki

AU - Kosugi, Shizuko

AU - Yamamoto, Michiko

AU - Serita, Ryohei

AU - Kotake, Yoshifumi

AU - Takeda, Junzo

PY - 2003/6/1

Y1 - 2003/6/1

N2 - 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 μg · kg-1 · min-1 olprinone; n = 10), or a high-dose group (0.6 μg · kg-1 · 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.

AB - 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 μg · kg-1 · min-1 olprinone; n = 10), or a high-dose group (0.6 μg · kg-1 · 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.

UR - http://www.scopus.com/inward/record.url?scp=0038104736&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0038104736&partnerID=8YFLogxK

U2 - 10.1097/00000542-200306000-00016

DO - 10.1097/00000542-200306000-00016

M3 - Article

C2 - 12766650

AN - SCOPUS:0038104736

VL - 98

SP - 1407

EP - 1414

JO - Anesthesiology

JF - Anesthesiology

SN - 0003-3022

IS - 6

ER -