title: Esmolol: immunomodulator in pyelonephritis by Pseudomonas aeruginosa.
abstract: BACKGROUND
  Based on previous animal studies showing promising immunomodulatory efficacy esmolol, a selective β1-blocker, it was assumed that administration of esmolol in experimental pyelonephritis by multidrug-resistant Pseudomonas aeruginosa would prolong survival and modulate immune response.
  
  
  METHODS
  Acute pyelonephritis was induced in 80 rabbits and assigned to eight groups receiving normal saline (controls), esmolol, amikacin, or both agents as pretreatment and as treatment. Blood was sampled for measurement of malondialdehyde and tumor necrosis factor alpha. Animals were followed up for survival, and after death quantitative tissue cultures were performed. The in vitro effect of esmolol on bacterial growth and on the oxidative burst of neutrophils of healthy controls and of sepsis patients was studied.
  
  
  RESULTS
  Survival of pretreatment groups administered single esmolol or esmolol and amikacin was prolonged compared with that of controls (P = 0.018 and P = 0.014, respectively); likewise, survival of treatment groups administered single esmolol or both agents was prolonged compared with that of controls (P = 0.007 and P = 0.014, respectively). Circulating malondialdehyde was significantly lower in pretreated animals administered esmolol or esmolol and amikacin compared with that in controls and in treated animals administered both agents compared with in controls (P = 0.020). In these groups, the bacterial load of the lung was significantly lower compared with controls. Serum tumor necrosis factor alpha did not change. Amikacin was increased in serum of esmolol-treated animals at levels which inhibited the in vitro growth of the studied isolate. Esmolol did not modify the in vitro growth of P aeruginosa and the oxidative burst of neutrophils.
  
  
  CONCLUSIONS
  It is concluded that esmolol prolonged survival after experimental infection by multidrug-resistant P aeruginosa. Survival benefit may be related with pleiotropic actions connected with modulation of pharmacokinetics and attenuation of inflammation.
authors.affiliation: 2nd Department of Critical Care Medicine, University of Athens Medical School, Athens, Greece.
authors.forename: George
authors.initials: G
authors.lastname: Dimopoulos
authors.affiliation: 2nd Department of Critical Care Medicine, University of Athens Medical School, Athens, Greece.
authors.forename: Maria
authors.initials: M
authors.lastname: Theodorakopoulou
authors.affiliation: 2nd Department of Critical Care Medicine, University of Athens Medical School, Athens, Greece.
authors.forename: Apostolos
authors.initials: A
authors.lastname: Armaganidis
authors.affiliation: 4th Department of Internal Medicine, University of Athens Medical School, Athens, Greece.
authors.forename: Ira-Maria
authors.initials: IM
authors.lastname: Tzepi
authors.affiliation: 2nd Department of Critical Care Medicine, University of Athens Medical School, Athens, Greece.
authors.forename: Michael
authors.initials: M
authors.lastname: Lignos
authors.affiliation: 4th Department of Internal Medicine, University of Athens Medical School, Athens, Greece.
authors.forename: Evangelos J
authors.initials: EJ
authors.lastname: Giamarellos-Bourboulis
authors.affiliation: 4th Department of Internal Medicine, University of Athens Medical School, Athens, Greece. Electronic address: tsag@freemail.gr.
authors.forename: Thomas
authors.initials: T
authors.lastname: Tsaganos
mesh_terms: D058671:Adrenergic beta-1 Receptor Antagonists / Q000627:therapeutic use*; D000818:Animals; D024901:Drug Resistance, Multiple, Bacterial; D005260:Female; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use*; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D011412:Propanolamines / Q000627:therapeutic use*; D011552:Pseudomonas Infections / Q000188:drug therapy* / Q000401:mortality; D011550:Pseudomonas aeruginosa / Q000187:drug effects; D011704:Pyelonephritis / Q000188:drug therapy* / Q000401:mortality; D011817:Rabbits
chemical_list: D058671:Adrenergic beta-1 Receptor Antagonists; D007155:Immunologic Factors; D011412:Propanolamines; D008315:Malondialdehyde; C036604:esmolol
keywords: Esmolol; Malondialdehyde; Multidrug resistance; Pyelonephritis; Sepsis