Recurrent episodes of gram-negative bacteremia or endotoxemia change reactivity of pre- and post-capillary pulmonary segments to angiotensin or free radicals.
OBJECTIVE
Recurrent episodes of Gram-negative bacteremia (from intraperitoneal abscesses) or endotoxemia cause lung microvascular injury in the rat. Change in vascular reactivity was assessed in response to challenge.


METHODS
In the isolated lung preparation, resistance was partitioned between pre-(PVRa) and post-capillary (PRVv) segments: vasoreactivity was assessed by challenge with Angiotensin II (AII) or reactive oxygen metabolites. Animals received 4 weekly intra-abdominal implants of live E. coli and B. fragilis in a carrier of sterile cecal content and barium sulfate (SEPSIS) or carrier alone (SHAM SEPSIS): or 4 weekly intravenous infusion of E. coli endotoxin (ENDO) or of saline (SHAM ENDO). A fifth group were untreated controls (CONTROL).


RESULTS
In the SEPSIS and ENDO lungs, PVRa and PVRv before challenge were normal. In the SEPSIS lung, AII increased PVRa more than in the control lung, PVRv to a similar degree in both. In the ENDO lung it increased PVRa compared with its effect on the SHAM ENDO lung: In both it also increased PVRv, to a similar degree and well above the baseline. Always tachyphylaxis developed with increases in dosage (to 25 microns and 50 microns, respectively). Oxygen free radical challenge in the SEPSIS and ENDO lung caused significant vasoconstriction, particularly PVRv, whereas no response was observed in the CONTROL or SHAM-treated lung from either group.


CONCLUSIONS
Abnormal lung vascular reactivity after SEPSIS or ENDOTOXIN is evident on challenge, the two agents used here detecting site specific changes.
Kirton
O C
OC
Department of Pathology, Children's Hospital, Boston, MA.
Gore
R G
RG
Reid
L M
LM
Jones
R C
RC
D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D016470:Bacteremia / Q000503:physiopathology*; D002196:Capillaries / Q000187:drug effects / Q000503:physiopathology; D005609:Free Radicals; D016905:Gram-Negative Bacterial Infections / Q000503:physiopathology*; D008168:Lung / Q000098:blood supply*; D008297:Male; D010100:Oxygen / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D012008:Recurrence; D014115:Toxemia / Q000503:physiopathology*; D014655:Vascular Resistance
D005609:Free Radicals; D000804:Angiotensin II; D010100:Oxygen