Effects of the angiotensin converting enzyme inhibitor enalapril on bacterial translocation after thermal injury and bacterial challenge.
Burn injury and sepsis produce acute gastrointestinal derangements that may predispose patients to bacterial translocation. We studied the effects of enalapril, an angiotensin converting enzyme inhibitor (ACEI), on gastrointestinal anatomic alterations, bacterial translocation, and related mortality during gut-derived sepsis in burned mice that had received a prior bacterial challenge. BALB/c mice (n = 111) were treated with enalapril 10 or 1 mg/kg body weight or sterile saline as control twice daily for 3 days. They were then gavaged with 10(a)111 in radiolabeled or unlabeled Escherichia coli and given a 20% total body surface area (TBSA) burn injury. Animals gavaged with unlabeled bacteria were observed for survival (n = 60). Survival was significantly higher in the group receiving enalapril 10 mg/Kg compared with control (75% vs. 10%). Mice treated with enalapril maintained small intestine weight, measured 4 h postburn, and ileal mucosal height was preserved, whereas burned untreated animals lost intestinal weight and mucosal height. Bacterial translocation was decreased in mice treated with enalapril, but killing was unaffected. This study suggests that treatment with enalapril positively affects the outcome in gut-derived sepsis by ameliorating gastrointestinal structural and functional damage and decreasing bacterial translocation.
Gennari
R
R
University of Cincinnati College of Medicine, Department of Surgery, Ohio 45267, USA.
Alexander
J W
JW
Boyce
S T
ST
Lilly
N
N
Babcock
G F
GF
Cornaggia
M
M
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D002056:Burns / Q000150:complications*; D004353:Drug Evaluation, Preclinical; D004656:Enalapril / Q000494:pharmacology* / Q000627:therapeutic use; D004926:Escherichia coli / Q000502:physiology*; D005260:Female; D007422:Intestines / Q000098:blood supply / Q000382:microbiology* / Q000503:physiopathology; D051379:Mice; D008807:Mice, Inbred BALB C; D018805:Sepsis / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D013152:Splanchnic Circulation / Q000187:drug effects*
D000806:Angiotensin-Converting Enzyme Inhibitors; D004656:Enalapril