PMID- 11193275
OWN - NLM
STAT- MEDLINE
DCOM- 20010322
LR  - 20190826
IS  - 0342-4642 (Print)
IS  - 0342-4642 (Linking)
VI  - 26
IP  - 11
DP  - 2000 Nov
TI  - Hemodynamic, biochemical and morphological changes induced by aminoguanidine in 
      normal and septic sheep.
PG  - 1670-80
AB  - OBJECTIVE: To define the acute hemodynamic, metabolic, and morphological changes 
      induced by aminoguanidine, a selective iNOS inhibitor, in septic sheep. DESIGN: 
      Prospective, nonrandomized animal study. SETTING: Animal research facility in a 
      University Hospital. INTERVENTIONS: Adult sheep, sedated and mechanically 
      ventilated, were monitored with a pulmonary arterial catheter and an ultrasonic 
      blood flow probe in the mesenteric artery, to measure the systemic (Q(TOT)I) and 
      the mesenteric (Q(MES)I) blood flow indices, and an ileal tonometer. Four groups 
      of sheep were studied: nonseptic, septic, nonseptic treated with aminoguanidine, 
      and septic treated with aminoguanidine (100 mg kg(-1) h(-1)) (n = 6 for each 
      group). Sepsis was induced by the intravenous administration of E. coli. 
      Hemodynamic and biochemical parameters were measured during 300 min. Histological 
      changes in the liver and small intestinal mucosa were analyzed at the end of the 
      experiment. MEASUREMENTS AND MAIN RESULTS: In nonseptic animals, aminoguanidine 
      slightly increased mean systemic arterial pressure (MAP), decreased Q(TOT)I, and 
      increased vascular resistance index (SVRI) and pulmonary vascular resistance 
      index. Q(MEs)I did not change and Q(MES)I/Q(ToT)I increased. Aminoguanidine also 
      induced intestinal intramucosal hypercarbia, hyperlactatemia, acidemia, 
      hypoglycemia, and morphological signs indicative of tissue ischemia in the small 
      intestinal mucosa. In septic sheep, aminoguanidine increased SVRI and MAP only at 
      4 h after the septic challenge and thereafter, and worsened gas exchange. 
      CONCLUSIONS: In this model, exogenous administration of aminoguanidine induces 
      beneficial hemodynamic effects 4 h after the septic challenge. In normal animals, 
      however, aminoguanidine was associated with hypoglycemia, acidosis, 
      hyperlactatemia, and intestinal mucosal ischemia.
FAU - Lorente, J A
AU  - Lorente JA
AD  - Servicio de Cuidados Intensivos, Hospital Universitario de Getafe, Madrid, Spain. 
      j.a.lorente@teleline.es
FAU - Tejedor, C
AU  - Tejedor C
FAU - Delgado, M A
AU  - Delgado MA
FAU - Fernandez-Segoviano, P
AU  - Fernandez-Segoviano P
FAU - Jara, N
AU  - Jara N
FAU - Tobalina, R
AU  - Tobalina R
FAU - Rodriguez-Corcos, A
AU  - Rodriguez-Corcos A
FAU - Moscoso, A
AU  - Moscoso A
FAU - Esteban, A
AU  - Esteban A
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Intensive Care Med
JT  - Intensive care medicine
JID - 7704851
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Guanidines)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase)
RN  - J2B2A4N98G (Lactose)
RN  - SCQ4EZQ113 (pimagedine)
SB  - IM
MH  - Acidosis/chemically induced
MH  - Analysis of Variance
MH  - Animals
MH  - Blood Pressure/drug effects
MH  - Case-Control Studies
MH  - Enzyme Inhibitors/*pharmacology/therapeutic use
MH  - Guanidines/*pharmacology/therapeutic use
MH  - Hemodynamics/*drug effects
MH  - Hypoglycemia/chemically induced
MH  - Intestinal Mucosa/blood supply/drug effects
MH  - Ischemia/chemically induced
MH  - Lactose/blood
MH  - Multiple Organ Failure/prevention & control
MH  - Nitric Oxide Synthase/*antagonists & inhibitors
MH  - Prospective Studies
MH  - Sepsis/*drug therapy
MH  - Sheep
MH  - Time Factors
MH  - Vascular Resistance/drug effects
MH  - Vasoconstriction/drug effects
EDAT- 2001/02/24 12:00
MHDA- 2001/03/27 10:01
CRDT- 2001/02/24 12:00
PHST- 2001/02/24 12:00 [pubmed]
PHST- 2001/03/27 10:01 [medline]
PHST- 2001/02/24 12:00 [entrez]
AID - 10.1007/s001340000673 [doi]
PST - ppublish
SO  - Intensive Care Med. 2000 Nov;26(11):1670-80. doi: 10.1007/s001340000673.