title: THAM reduces CO2-associated increase in pulmonary vascular resistance - an experimental study in lung-injured piglets.
abstract: BACKGROUND
  Low tidal volume (VT) ventilation is recommended in patients with acute respiratory distress syndrome (ARDS). This may increase arterial carbon dioxide tension (PaCO2), decrease pH, and augment pulmonary vascular resistance (PVR). We hypothesized that Tris(hydroxymethyl)aminomethane (THAM), a pure proton acceptor, would dampen these effects, preventing the increase in PVR.
  
  
  METHODS
  A one-hit injury ARDS model was established by repeated lung lavages in 18 piglets. After ventilation with VT of 6 ml/kg to maintain normocapnia, VT was reduced to 3 ml/kg to induce hypercapnia. Six animals received THAM for 1 h, six for 3 h, and six serving as controls received no THAM. In all, the experiment continued for 6 h. The THAM dosage was calculated to normalize pH and exhibit a lasting effect. Gas exchange, pulmonary, and systemic hemodynamics were tracked. Inflammatory markers were obtained at the end of the experiment.
  
  
  RESULTS
  In the controls, the decrease in VT from 6 to 3 ml/kg increased PaCO2 from 6.0±0.5 to 13.8±1.5 kPa and lowered pH from 7.40±0.01 to 7.12±0.06, whereas base excess (BE) remained stable at 2.7±2.3 mEq/L to 3.4±3.2 mEq/L. In the THAM groups, PaCO2 decreased and pH increased above 7.4 during the infusions. After discontinuing the infusions, PaCO2 increased above the corresponding level of the controls (15.2±1.7 kPa and 22.6±3.3 kPa for 1-h and 3-h THAM infusions, respectively). Despite a marked increase in BE (13.8±3.5 and 31.2±2.2 for 1-h and 3-h THAM infusions, respectively), pH became similar to the corresponding levels of the controls. PVR was lower in the THAM groups (at 6 h, 329±77 dyn∙s/m(5) and 255±43 dyn∙s/m(5) in the 1-h and 3-h groups, respectively, compared with 450±141 dyn∙s/m(5) in the controls), as were pulmonary arterial pressures.
  
  
  CONCLUSIONS
  The pH in the THAM groups was similar to pH in the controls at 6 h, despite a marked increase in BE. This was due to an increase in PaCO2 after stopping the THAM infusion, possibly by intracellular release of CO2. Pulmonary arterial pressure and PVR were lower in the THAM-treated animals, indicating that THAM may be an option to reduce PVR in acute hypercapnia.
authors.affiliation: Hedenstierna Laboratory, Uppsala University, Uppsala, Sweden. staffan.hostman@surgsci.uu.se.|Department of Surgical Sciences, Uppsala University Hospital, Entrance 70, 75185, Uppsala, Sweden. staffan.hostman@surgsci.uu.se.
authors.forename: Staffan
authors.initials: S
authors.lastname: Höstman
authors.affiliation: Hedenstierna Laboratory, Uppsala University, Uppsala, Sweden. joao.batista_borges@medsci.uu.se.|Department of Surgical Sciences, Uppsala University Hospital, Entrance 70, 75185, Uppsala, Sweden. joao.batista_borges@medsci.uu.se.|Cardio-Pulmonary Department, Pulmonary Division, Heart Institute (Incor), University of São Paulo, São Paulo, Brazil. joao.batista_borges@medsci.uu.se.
authors.forename: João Batista
authors.initials: JB
authors.lastname: Borges
authors.affiliation: Hedenstierna Laboratory, Uppsala University, Uppsala, Sweden. fsuarezsipmann@gmail.com.|Department of Surgical Sciences, Uppsala University Hospital, Entrance 70, 75185, Uppsala, Sweden. fsuarezsipmann@gmail.com.
authors.forename: Fernando
authors.initials: F
authors.lastname: Suarez-Sipmann
authors.affiliation: Hedenstierna Laboratory, Uppsala University, Uppsala, Sweden. kerstin.ahlgren@surgsci.uu.se.|Department of Surgical Sciences, Uppsala University Hospital, Entrance 70, 75185, Uppsala, Sweden. kerstin.ahlgren@surgsci.uu.se.
authors.forename: Kerstin M
authors.initials: KM
authors.lastname: Ahlgren
authors.affiliation: Hedenstierna Laboratory, Uppsala University, Uppsala, Sweden. joakim@me.com.|Department of Surgical Sciences, Uppsala University Hospital, Entrance 70, 75185, Uppsala, Sweden. joakim@me.com.
authors.forename: Joakim
authors.initials: J
authors.lastname: Engström
authors.affiliation: Hedenstierna Laboratory, Uppsala University, Uppsala, Sweden. goran.hedenstierna@medsci.uu.se.|Department of Medical Sciences, Uppsala University, Uppsala, Sweden. goran.hedenstierna@medsci.uu.se.
authors.forename: Göran
authors.initials: G
authors.lastname: Hedenstierna
authors.affiliation: Hedenstierna Laboratory, Uppsala University, Uppsala, Sweden. anders.larsson@surgsci.uu.se.|Department of Surgical Sciences, Uppsala University Hospital, Entrance 70, 75185, Uppsala, Sweden. anders.larsson@surgsci.uu.se.
authors.forename: Anders
authors.initials: A
authors.lastname: Larsson
mesh_terms: D000818:Animals; D002245:Carbon Dioxide / Q000009:adverse effects* / Q000378:metabolism; D004195:Disease Models, Animal; D006439:Hemodynamics / Q000502:physiology; D006935:Hypercapnia / Q000188:drug therapy* / Q000628:therapy; D008168:Lung / Q000187:drug effects; D012128:Respiratory Distress Syndrome / Q000209:etiology* / Q000473:pathology; D013552:Swine; D013990:Tidal Volume / Q000502:physiology; D014325:Tromethamine / Q000009:adverse effects / Q000627:therapeutic use*; D014655:Vascular Resistance / Q000502:physiology*; D055397:Ventilator-Induced Lung Injury / Q000150:complications / Q000473:pathology
chemical_list: D014325:Tromethamine; D002245:Carbon Dioxide