Effects of low-dose Beraprost sodium, a stable prostaglandin I2 analogue, on reperfusion injury to rabbit lungs.
We investigated the effects of low-dose Beraprost sodium (BPS), a stable prostaglandin I2 (PGI2) analogue, on microvascular permeability and the plasma concentrations of thromboxane and adenosine 3',5'-cyclic monophosphate (cAMP) in blood-perfused rabbit lungs subjected to ischemia-reperfusion (I/R). After an ischemic insult for 2 h, saline as a vehicle, 3 pmol/L of BPS (BPS-1), 150 to 300 pmol/L of BPS (BPS-2), 900 pmol/L of BPS (BPS-3), or 60 micromol/L of indomethacin (IND) was administered into the reservoir, then the lungs were reperfused and reventilated for 1 h. Vascular permeability was assessed by determining the microvascular filtration coefficient (Kf, ml/min/mm Hg/100 g wet lung). I/R resulted in increases in vascular resistance, Kf, and thromboxane. BPS-2, BPS-3, and IND inhibited the increase in vascular resistance, and BPS-3 and IND attenuated the increases in Kf and thromboxane. BPS-3 increased, but IND decreased, the concentrations of cAMP in the perfusate. Perfusate thromboxane released after reperfusion was significantly correlated with Kf. We conclude that cyclooxygenase products play a critical role in I/R-induced lung vascular injury and that 900 pmol/L of BPS inhibits the production of thromboxane and enhances the permeability barrier via a cAMP-elevating effect. However, vasodilatory action of BPS may exacerbate the reperfused lung injury by increasing the flow through injured capillaries via inhibition of thromboxane-induced vasoconstriction.
Jiang
X W
XW
Second Department of Internal Medicine, Gifu University School of Medicine, Hakuaikai General Hospital, Gifu, Japan.
Kambara
K
K
Gotoh
N
N
Nishigaki
K
K
Fujiwara
H
H
D015121:6-Ketoprostaglandin F1 alpha / Q000097:blood; D000704:Analysis of Variance; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects; D002196:Capillaries / Q000187:drug effects; D002199:Capillary Permeability / Q000187:drug effects; D000242:Cyclic AMP / Q000097:blood; D011464:Epoprostenol / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D007213:Indomethacin / Q000008:administration & dosage / Q000627:therapeutic use; D008168:Lung / Q000098:blood supply / Q000187:drug effects / Q000473:pathology; D008171:Lung Diseases / Q000097:blood / Q000188:drug therapy*; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D011817:Rabbits; D015427:Reperfusion Injury / Q000097:blood / Q000188:drug therapy*; D012121:Respiration, Artificial; D013929:Thromboxane B2 / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis; D014655:Vascular Resistance / Q000187:drug effects; D014664:Vasodilation; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000627:therapeutic use*
D000893:Anti-Inflammatory Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; D014409:Tumor Necrosis Factor-alpha; D014665:Vasodilator Agents; C048081:beraprost; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; D011464:Epoprostenol; D000242:Cyclic AMP; D007213:Indomethacin