Prostaglandin E1 attenuation of ischemic renal reperfusion injury in the rat.
BACKGROUND
Prostaglandin E1 (PGE1), a vasodilating prostaglandin, has been shown to protect against renal ischemic-reperfusion injury in acute experiments. The purpose of this study was to determine whether or not delayed administration of PGE1 would also be effective, as it has been suggested to be, in ischemic hepatic injury.


METHODS
In a chronic model, rats underwent 60 minutes of total renal ischemia followed by either NaCl or PGE1 therapy delivered at either time 0, 30, or 60 minutes after reperfusion. Serum creatinine and renal histology were evaluated for seven days. In an isolated perfused kidney model, kidneys were similarly treated but were removed and perfused in order to measure renal vascular resistance (VR).


RESULTS
Prostaglandin E1 administration at time 0 resulted in lower creatinine values when compared with controls at both day 2 (2.1 +/- 0.4 compared with 4.2 +/- 0.9 mg/dL) and day 7 (0.9 +/- 0.1 compared with 2.3 +/- 0.8 mg/dL). Conversely, no improvement was observed when PGE1 was delayed for either 30 or 60 minutes. Renal morphology at seven days was essentially intact in PGE1-treated rats (time 0) whereas changes characteristic of acute tubular necrosis were observed in control kidneys. Ischemia caused a twofold increase in VR compared with nonischemic controls (6.18 +/- 1.12 compared with 3.45 +/- 0.66 mm Hg/mL/min/g at 20 minutes of perfusion). Prostaglandin E1-treated kidneys (time 0) had a VR that was unchanged from that calculated for nonischemic controls (3.28 +/- 0.63 compared with 3.45 +/- 0.66 mm Hg/mL/min/g at 20 minutes).


CONCLUSIONS
These data demonstrate that after total renal ischemia, PGE1 administration at reperfusion ameliorates the expected injury, whereas delayed treatment is ineffective. Decreased vascular resistance may be responsible for this protective effect.
Vargas
A V
AV
Department of Surgery, Case Western Reserve University, Cleveland, OH, USA.
Krishnamurthi
V
V
Masih
R
R
Robinson
A V
AV
Schulak
J A
JA
D000527:Alprostadil / Q000627:therapeutic use*; D000818:Animals; D003404:Creatinine / Q000097:blood; D007668:Kidney / Q000098:blood supply* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D051381:Rats; D011917:Rats, Inbred Lew; D012077:Renal Artery / Q000503:physiopathology; D015427:Reperfusion Injury / Q000097:blood / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D014655:Vascular Resistance
D003404:Creatinine; D000527:Alprostadil