An adult canine model of chronic pulmonary hypertension for cardiopulmonary transplantation.
BACKGROUND
This study establishes a chemically-induced canine model of chronic pulmonary hypertension (CPH) using monocrotaline pyrrole (MCTP) and then characterizes this model in terms of hemodynamic, morphologic, and cardiac functional changes.


METHODS
Thirty-three adult mongrel dogs (22 to 25 kg) were used. All animals underwent pulmonary artery catheterization to measure central venous pressure, mean right ventricular pressure (mRVP), mean pulmonary artery pressure (mPAP), and pulmonary capillary wedge pressure before and 6 weeks after a right atrial injection of either 60 mg/kg monocrotaline (group A, n = 8), 5 mg/kg MCTP (group B, n = 4), 3 mg/kg MCTP (group C, n = 13) or placebo (control, n = 8). Six weeks after injection, hearts in control and group C dogs were instrumented with flow probes, dimension transducers, and micromanometers to measure dynamic ventricular pressures and volumes.


RESULTS
No significant differences in baseline hemodynamic indexes were observed between groups. All animals in group B and five in group C died after MCTP injection as a result of pulmonary edema. No significant increase in any hemodynamic parameters occurred in group A or in control dogs 6 weeks after injection. In group C, significant increases in central venous pressure, mRVP, and mPAP were observed 6 weeks after injection. Significant increases in right ventricular (RV) function and the weight ratio of the RV to left ventricle were observed in group C when compared with controls.


CONCLUSIONS
A chemically-induced canine model of CPH has been created. Significant increases in mRVP, mPAP, and pulmonary capillary wedge pressure were observed 6 weeks after MCTP injection. RV function adapts to the increased afterload in the short term without evidence of failure. A stable model of pulmonary hypertension is provided as a potential means to evaluate posttransplantation RV dysfunction in the setting of CPH.
Chen
E P
EP
Department of General and Thoracic Surgery, Duke University Medical Center, Durham, North Carolina, USA.
Bittner
H B
HB
Tull
F
F
Biswas
S S
SS
Davis
R D
RD
Van Trigt
P
P
D000367:Age Factors; D000818:Animals; D002407:Catheterization, Swan-Ganz; D002908:Chronic Disease; D004195:Disease Models, Animal; D004285:Dogs; D016041:Heart-Lung Transplantation / Q000379:methods*; D006439:Hemodynamics; D006976:Hypertension, Pulmonary / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology / Q000601:surgery*; D016686:Monocrotaline / Q000031:analogs & derivatives / Q000737:chemistry; D015203:Reproducibility of Results; D016276:Ventricular Function
C014114:monocrotaline pyrrole; D016686:Monocrotaline