| Acadesine during fluid resuscitation from shock and abdominal sepsis. | |
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MedLine Citation:
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PMID: 10199538 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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OBJECTIVE: To determine properties of acadesine, the prototype adenosine regulating agent, in an experimental model in which abdominal sepsis is superimposed onto hemorrhagic shock. DESIGN: Randomized, blinded animal study. SETTING: University-based animal research facility. SUBJECTS: Twenty-eight anesthetized mongrel pigs (35.5 +/- 1.1 kg). INTERVENTIONS: The cecum was ligated and punctured to produce abdominal sepsis. To produce hemorrhagic shock, 45% to 47% of the estimated blood volume was withdrawn. After 1 hr, shed blood plus supplemental crystalloid (twice the shed blood volume) plus either acadesine (5 mg/kg bolus + 1 mg/kg x 60 min, n = 10) or its vehicle (n = 10) was administered. All animals were awakened and observed for 48 hrs. At 48 hrs, cardiac function, bacterial cultures from the septic focus, and inflammatory changes in the abdomen were quantified. MEASUREMENTS AND MAIN RESULTS: After resuscitation with acadesine vs. vehicle, we observed the following: a) arterial blood pressure and cardiac filling pressures were similar but cardiac index, systemic oxygen delivery, and systemic oxygen consumption were increased; b) plasma lactate was higher, systemic vascular resistance was lower, but ileal mucosal blood flow was not measurably altered; c) lipopolysaccharide-evoked tumor necrosis factor production in whole blood ex vivo was reduced; d) in those animals that survived 48 hrs (10/10 vs. 8/10), sepsis-induced cardiac depression, amount of free intraperitoneal fluid, extra abscess inflammatory reaction, abscess wall formation, abscess bacterial counts, and peritoneal bacterial counts, were all similar, but blood bacterial counts were higher. CONCLUSIONS: Fluid resuscitation with acadesine produced no adverse hemodynamic consequences and probably improved washout of metabolites from the reperfused microcirculation in sites other than the small intestine or heart. Taken together, these observations suggest that adenosine regulating agents might have therapeutic potential during fluid resuscitation from trauma. However, at least in these extreme conditions, the acute salutary effects of acadesine were probably overwhelmed by polymicrobial sepsis. Further studies must determine whether supplemental adjuvants to boost host defense during recovery from trauma will optimize adenosine-based resuscitation solutions. |
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Authors:
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S M Melton; C B Moomey; D N Ragsdale; L L Trenthem; M A Croce; T C Fabian; K G Proctor |
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Publication Detail:
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Type: Journal Article; Research Support, U.S. Gov't, Non-P.H.S.; Review |
Journal Detail:
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Title: Critical care medicine Volume: 27 ISSN: 0090-3493 ISO Abbreviation: Crit. Care Med. Publication Date: 1999 Mar |
Date Detail:
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Created Date: 1999-04-27 Completed Date: 1999-04-27 Revised Date: 2007-11-15 |
Medline Journal Info:
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Nlm Unique ID: 0355501 Medline TA: Crit Care Med Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 565-75 Citation Subset: AIM; IM |
Affiliation:
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Department of Surgery, University of Tennessee, Memphis 38163, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Aminoimidazole Carboxamide
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analogs & derivatives*,
therapeutic use Animals Cecum / injuries Female Fluid Therapy* Hemodynamics / drug effects* Intestinal Mucosa / blood supply, drug effects Leukocyte Count Ligation Male Oxygen Consumption Random Allocation Reperfusion Injury / prevention & control Resuscitation / methods* Ribonucleosides / therapeutic use* Sepsis / complications, drug therapy*, metabolism Shock, Hemorrhagic / complications, therapy* Swine Tumor Necrosis Factor-alpha / metabolism |
| Chemical | |
Reg. No./Substance:
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0/Ribonucleosides; 0/Tumor Necrosis Factor-alpha; 2627-69-2/acadesine; 360-97-4/Aminoimidazole Carboxamide |
| Comments/Corrections | |
Comment In:
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Crit Care Med. 1999 Mar;27(3):468-9
[PMID:
10199518
]
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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