title: Right ventricle-sparing heart transplantation effective against iatrogenic pulmonary hypertension.
abstract: BACKGROUND
  Right heart failure is the predominant cause of death following heart transplantation, occurring with disturbingly high frequency in patients with severe antecedent pulmonary hypertension. We have recently reported a novel technique of heart transplantation that spares the recipient right ventricle, excising only the recipient left ventricle. The resulting model has 2 right hearts and 1 left heart. The aim is to preserve the recipient's right ventricle, which is already conditioned to pulmonary hypertension. The hope is that, in this way, death due to right heart failure can be prevented in humans. Our prior report was a feasibility study in normal dogs. This study challenges this new technique by creating iatrogenic pulmonary hypertension in the recipient animals.
  
  
  METHODS
  Iatrogenic pulmonary hypertension was created in 4 recipient canines by intravenous injection of the pulmonary toxin monocrotaline pyrrole (single bolus of 3.5 to 4.5 mg/kg intravenously [i.v.]).
  
  
  RESULTS
  Within 6 weeks of monocrotaline administration, relative pulmonary hypertension occurred (mean pulmonary artery [PA] pressure 20 mm Hg vs 10 mm Hg for controls [p < 0.01]) (pulmonary vascular resistance [PVR] 4.2 vs 1.5 Wood units [P < 0.01]), and right ventricular (RV) hypertrophy developed (RV thickness 11 mm vs 2 mm [P < 0.04]). Histologic examination confirmed severe muscle infiltration and thickening of the media of the pulmonary arterioles. RV-sparing heart transplantation was performed successfully in all 4 animals with pulmonary hypertension. In all cases, the animals were weaned without difficulty from cardiopulmonary bypass, despite the ambient pulmonary hypertension, on low-dose epinephrine, maintaining systolic blood pressure of 104 mm Hg at right atrial pressure of 7 mm Hg. Both right hearts contracted well without dilation or strain. A single "control" traditional orthotopic transplant experiment in an animal with monocrotaline-induced pulmonary hypertension resulted in immediate death from right heart failure.
  
  
  CONCLUSIONS
  Right ventricle-sparing heart transplantation ("one-and-one-half heart model") can handle pulmonary hypertension without difficulty. This evidence adds impetus for further pursuing of right ventricle-sparing heart transplantation to decrease the incidence of death from right heart failure in recipients with severe antecedent pulmonary hypertension.
authors.affiliation: Section of Cardiothoracic Surgery, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
authors.forename: Constantinos
authors.initials: C
authors.lastname: Lovoulos
authors.forename: Shawn
authors.initials: S
authors.lastname: Tittle
authors.forename: Lee
authors.initials: L
authors.lastname: Goldstein
authors.forename: David J
authors.initials: DJ
authors.lastname: Austin
authors.forename: Simran
authors.initials: S
authors.lastname: Singh
authors.forename: Edward
authors.initials: E
authors.lastname: Rocco
authors.forename: James
authors.initials: J
authors.lastname: Keane
authors.forename: Ping
authors.initials: P
authors.lastname: Tang
authors.forename: Gary S
authors.initials: GS
authors.lastname: Kopf
authors.forename: John A
authors.initials: JA
authors.lastname: Elefteriades
mesh_terms: D000477:Alkylating Agents; D000818:Animals; D004285:Dogs; D016027:Heart Transplantation / Q000379:methods*; D006352:Heart Ventricles; D006976:Hypertension, Pulmonary / Q000139:chemically induced / Q000503:physiopathology*; D017380:Hypertrophy, Right Ventricular / Q000209:etiology / Q000503:physiopathology; D007049:Iatrogenic Disease; D016686:Monocrotaline / Q000031:analogs & derivatives*
chemical_list: D000477:Alkylating Agents; C014114:monocrotaline pyrrole; D016686:Monocrotaline