Postischemic renal injury is mediated by neutrophils and leukotrienes.
Neutrophils have been implicated as central mediators in myocardial and skeletal muscle ischemia-reperfusion injury. This study tests whether these cellular elements and the chemoattractant leukotriene (LTB4) play a role in postischemic renal failure. Anesthetized rats underwent 45 min of left renal pedicle clamping. Five minutes after reperfusion, LTB4 levels were elevated to 1.42 ng/ml (P less than 0.05); thromboxane (Tx)B2 was 2,840 pg/ml, higher than 503 pg/ml in sham controls (P less than 0.05); renal artery blood flow was 67% of preclamping values at 1 min of reperfusion compared with 111% in sham (P less than 0.05). At 24 h, creatinine levels were 4.6 mg/dl (P less than 0.05). At 24 h, creatinine levels were 4.6 mg/dl (P less than 0.05); histology showed acute tubular necrosis (ATN). Neutrophil depletion by rabbit antiserum (n = 8) led during reperfusion to reduced LTB4 and TxB2 levels, 1.04 ng/ml and 1.043 pg/ml (P less than 0.05); increased renal blood flow of 174% (P less than 0.05); reduced creatinine levels of 1.8 mg/dl (P less than 0.05); and limited ATN. Pretreatment with diethycarbamazine prevented the increases in LTB4 and TxB2 (P less than 0.05), increased renal blood flow (P less than 0.05), minimized creatinine increase to 1.7 mg/dl (P less than 0.05), and reduced ATN. These data indicate that neutrophils and LTB4 play a role in ischemia-induced Tx synthesis and mediate postischemic renal injury.
Klausner
J M
JM
Department of Surgery, Brigham and Women's Hospital, Boston, Massachusetts.
Paterson
I S
IS
Goldman
G
G
Kobzik
L
L
Rodzen
C
C
Lawrence
R
R
Valeri
C R
CR
Shepro
D
D
Hechtman
H B
HB
D015121:6-Ketoprostaglandin F1 alpha / Q000097:blood; D000818:Animals; D004049:Diethylcarbamazine / Q000494:pharmacology; D007511:Ischemia / Q000473:pathology* / Q000503:physiopathology; D007668:Kidney / Q000473:pathology* / Q000503:physiopathology; D007958:Leukocyte Count; D007975:Leukotriene B4 / Q000097:blood / Q000502:physiology*; D008297:Male; D009504:Neutrophils / Q000473:pathology / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains; D012079:Renal Circulation; D012082:Renal Veins; D015424:Reperfusion; D013929:Thromboxane B2 / Q000097:blood
D007975:Leukotriene B4; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; D004049:Diethylcarbamazine