title: Resuscitation Using Liposomal Vasopressin in an Animal Model of Uncontrolled Hemorrhagic Shock.
abstract: BACKGROUND
  Current research suggests that administration of vasopressin to patients with uncontrolled hemorrhagic shock (UHS) can avoid the detrimental effects associated with aggressive fluid resuscitation. However, vasopressin has a short half-life of 10~35 minutes in in vivo use and precludes its use in the pre-hospital setting. To increase the half-life of vasopressin, we proposed to synthesize liposome-encapsulated vasopressin and test it in a rat model of UHS.
  
  
  METHODS
  The film hydration method was used to prepare liposomal vasopressin consisting of: Dipalmitoylphosphatidylcholine, cholesterol, and dipalmitoyl phosphatidylethanolamine (20:20:1 mole ratio). 42 rats were subjected to UHS and randomly received 5 different treatments (vasopressin, liposomal vasopressin, lactate ringer (LR), liposome only and sham). Outcome of UHS were measured using 4 common prognostic tests: mean arterial pressure (MAP), serum lactate level, inflammatory profile and pulmonary edema.
  
  
  RESULTS
  The dynamic light scattering results confirmed that we had prepared a successful liposomal vasopressin complex. Comparing the serum vasopressin concentration of liposomal vasopressin and vasopressin treated animals by ELISA, we found that the concentration of vasopressin for the liposomal vasopressin treated group is higher at 60 minutes. However, there was no significant difference between the MAP profile of rats treated with vasopressin and liposomal vasopressin in UHS. We also observed that animals treated with liposomal vasopressin performed indifferently to vasopressin treated rats in serum lactate level, inflammatory profile and edema profile. For most of our assays, the liposome only control behaves similarly to LR resuscitation in UHS rats.
  
  
  CONCLUSIONS
  We have synthesized a liposomal vasopressin complex that can prolong the serum concentration of vasopressin in a rat model of UHS. Although UHS rats treated with either liposomal vasopressin or vasopressin showed no statistical differences, it would be worthwhile to repeat the experiments with different liposomal compositions.
authors.affiliation: Department of Emergency Medicine, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Meng-Tse Gabriel
authors.initials: MT
authors.lastname: Lee
authors.affiliation: Department of Emergency Medicine, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Hsuan-Mao
authors.initials: HM
authors.lastname: Wang
authors.affiliation: Department of Biochemical Science and Technology, National Taiwan University, Taipei, Taiwan.
authors.forename: Ja-An Annie
authors.initials: JA
authors.lastname: Ho
authors.affiliation: Department of Biochemical Science and Technology, National Taiwan University, Taipei, Taiwan.
authors.forename: Nien-Chu
authors.initials: NC
authors.lastname: Fan
authors.affiliation: Department of Emergency Medicine, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Ya-Lin
authors.initials: YL
authors.lastname: Yang
authors.affiliation: Department of Emergency Medicine, National Taiwan University Hospital, Taipei, Taiwan; Department of Emergency Medicine, National Taiwan University Hospital Yunlin Branch, Douliou, Taiwan; Department of General Medicine, National Taiwan University Hospital Yunlin Branch, Douliou, Taiwan.
authors.forename: Chien-Chang
authors.initials: CC
authors.lastname: Lee
authors.affiliation: Department of Emergency Medicine, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Shyr-Chyr
authors.initials: SC
authors.lastname: Chen
mesh_terms: D015060:1,2-Dipalmitoylphosphatidylcholine / Q000737:chemistry; D000818:Animals; D002784:Cholesterol / Q000737:chemistry; D004195:Disease Models, Animal; D005440:Fluid Therapy; D015850:Interleukin-6 / Q000097:blood; D007552:Isotonic Solutions / Q000737:chemistry; D008027:Light; D008081:Liposomes / Q000737:chemistry*; D008297:Male; D010714:Phosphatidylethanolamines / Q000737:chemistry; D011654:Pulmonary Edema; D051381:Rats; D017208:Rats, Wistar; D012151:Resuscitation / Q000379:methods*; D000077325:Ringer's Lactate; D012542:Scattering, Radiation; D012771:Shock, Hemorrhagic / Q000503:physiopathology* / Q000628:therapy*; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D014667:Vasopressins / Q000737:chemistry / Q000627:therapeutic use*
chemical_list: D015850:Interleukin-6; D007552:Isotonic Solutions; D008081:Liposomes; D010714:Phosphatidylethanolamines; D000077325:Ringer's Lactate; D014409:Tumor Necrosis Factor-alpha; D014667:Vasopressins; D015060:1,2-Dipalmitoylphosphatidylcholine; C007510:1,2-dipalmitoyl-3-phosphatidylethanolamine; D002784:Cholesterol