AN ADULT CANINE MODEL OF CHRONIC PULMONARY-HYPERTENSION FOR CARDIOPULMONARY TRANSPLANTATION

Background: This study establishes a chemically-induced canine model o f chronic pulmonary hypertension (CPH) using monocrotaline pyrrole (MC TP) and then characterizes this model in terms of hemodynamic, morphol ogic, and cardiac functional changes. Methods: Thirty-three adult mong rel dogs (22 to 25 kg) were used. All animals underwent pulmonary arte ry catheterization to measure central venous pressure, mean right vent ricular pressure (mRVP), mean pulmonary artery pressure (mPAP), and pu lmonary capillary wedge pressure before and 6 weeks after a right atri al injection of either 60 mg/kg monocrotaline (group A, n = 8), 5 mg/k g MCTP (group B, n = 4), 3 mg/kg MCTP (group C, n = 13) or placebo (co ntrol, 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 we re observed between groups. Al animals in group B and five in group C died after MCTP injection as a result of pulmonary edema. No significa nt increase in any hemodynamic parameters occurred in group A or in co ntrol 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 a nd the weight ratio of the RV to left ventricle were observed in group C when compared with controls. Conclusions: A chemically-induced cani ne model of CPH has been created. Significant increases in mRVP, mPAP, and pulmonary capillary wedge pressure were observed 6 weeks after MC TP injection. RV function adapts to the increased afterload in the sho rt term without evidence of failure. A stable model of pulmonary hyper tension is provided as a potential means to evaluate posttransplantati on RV dysfunction in the setting of CPH.