title: Adrenomedullin induces pulmonary vasodilation but does not attenuate pulmonary hypertension in a sheep model of acute pulmonary embolism.
abstract: OBJECTIVE
  The pulmonary vasodilation induced by adrenomedullin may be beneficial in the acute pulmonary embolism (APE) setting. This study examined effects of adrenomedullin in sheep with microsphere-induced APE.
  
  
  METHODS
  Twenty four anesthetized, mechanically ventilated sheep were randomly assigned into 3 groups (n=8 per group): animals not subjected to any intervention (Sham), animals with APE induced by microspheres (500 mg, intravenously) treated 30 min later by intravenous physiological saline (Emb group) or intravenous adrenomedullin (50 ng/kg/min) during 30 min (Emb+Adm group). Plasma concentrations of cyclic adenosine (cAMP) and guanosine monophosphate (cGMP) were determined by enzyme immunoassay.
  
  
  RESULTS
  Variables did not change over time in sham animals. In both embolized groups, microsphere injection significantly (P<0.05) increased pulmonary vascular resistance index (PVRI) and mean pulmonary artery pressure (MPAP) from baseline by 181% and 111-142%, respectively (% change in mean values). Adrenomedullin significantly decreased PVRI (18%-25%) and significantly increased cardiac index (22%-25%) from values recorded 30 min after APE (E30), without modifying MPAP. Adrenomedullin decreased mean arterial pressure (18%-24%) and systemic vascular resistance index (32%-40%). Embolization significantly increased arterial-to-end tidal CO2 gradient, alveolar-to-arterial O2 gradient, and pulmonary shunt fraction from baseline, but these variables were unaffected by adrenomedullin. While adrenomedullin significantly increased plasma cAMP, cGMP levels were unaltered.
  
  
  CONCLUSIONS
  Adrenomedullin induces systemic and pulmonary vasodilation, possibly via a cAMP mediated mechanism, without modifying the gas exchange impairment associated with APE. The pulmonary anti-hypertensive effect of adrenomedullin may be offset by increases in cardiac index.
authors: Departamento de Anestesiologia, Faculdade de Medicina, Univ. Estadual Paulista (UNESP), Botucatu, São Paulo, Brazil.
authors: Angie Paola
authors: AP
authors: Lagos-Carvajal
authors: Departamento de Anestesiologia, Faculdade de Medicina, Univ. Estadual Paulista (UNESP), Botucatu, São Paulo, Brazil; Departamento de Cirurgia e Anestesiologia Veterinária, Faculdade de Medicina Veterinária e Zootecnia, Univ. Estadual Paulista (UNESP), Botucatu, São Paulo, Brazil.
authors: Francisco José
authors: FJ
authors: Teixeira-Neto
authors: Departamento de Cirurgia e Anestesiologia Veterinária, Faculdade de Medicina Veterinária e Zootecnia, Univ. Estadual Paulista (UNESP), Botucatu, São Paulo, Brazil.
authors: Diana Rocío
authors: DR
authors: Becerra-Velásquez
authors: Departamento de Anestesiologia, Faculdade de Medicina, Univ. Estadual Paulista (UNESP), Botucatu, São Paulo, Brazil.
authors: Miriely Steim
authors: MS
authors: Diniz
authors: Departamento de Anestesiologia, Faculdade de Medicina, Univ. Estadual Paulista (UNESP), Botucatu, São Paulo, Brazil.
authors: Adriana Vieira
authors: AV
authors: Klein
authors: Departamento de Farmacologia, Instituto de Biociências de Botucatu, Univ. Estadual Paulista (UNESP), Botucatu, São Paulo, Brazil.
authors: Thalita Leone Alves
authors: TL
authors: Rocha
authors: Departamento de Anestesiologia, Faculdade de Medicina, Univ. Estadual Paulista (UNESP), Botucatu, São Paulo, Brazil; Departamento de Farmacologia, Instituto de Biociências de Botucatu, Univ. Estadual Paulista (UNESP), Botucatu, São Paulo, Brazil. Electronic address: carlosjunior@ibb.unesp.br.
authors: Carlos Alan
authors: CA
authors: Dias-Junior
mesh_terms: D000208:Acute Disease; D053607:Adrenomedullin / Q000627:therapeutic use*; D000818:Animals; D000242:Cyclic AMP / Q000097:blood; D006152:Cyclic GMP / Q000097:blood; D004195:Disease Models, Animal; D006976:Hypertension, Pulmonary / Q000097:blood / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D008168:Lung / Q000098:blood supply / Q000187:drug effects* / Q000503:physiopathology; D008297:Male; D011655:Pulmonary Embolism / Q000097:blood / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D012756:Sheep; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000627:therapeutic use*
chemical_list: D014665:Vasodilator Agents; D053607:Adrenomedullin; D000242:Cyclic AMP; D006152:Cyclic GMP
keywords: Adrenomedullin; Pulmonary embolism; Pulmonary hypertension