FK506 (Tacrolimus) in Pulmonary Arterial Hypertension

Exclusion Criteria

• •1. WHO Group II - V Pulmonary Hypertension.
• •2. Current or prior experimental PAH treatments within the last 6 months (including but not limited to tyrosine kinase inhibitors, rho-kinase inhibitors, or cGMP modulators).
• •3. Current active treatment with the dual endothelin receptor antagonist bosentan.
• •4. TLC \< 60% predicted; if TLC b/w 60 and 70% predicted, high resolution computed tomography must be available to exclude significant interstitial lung disease.
• •5. FEV1 / FVC \< 70% predicted and FEV1 \< 60% predicted
• •6. Significant left-sided heart disease (based on screening Echocardiogram):
• •1. Significant aortic or mitral valve disease
• •2. Diastolic dysfunction ≥ Grade II
• •3. LV systolic function \< 45%
• •4. Pericardial constriction
• •5. Restrictive cardiomyopathy
• •6. Significant coronary disease with demonstrable ischemia.
• •7. Chronic renal insufficiency defined as an estimated creatinine clearance \< 30 ml/min (by MDRD equation).
• •8. Current atrial arrhythmias not under optimal control.
• •9. Uncontrolled systemic hypertension: SBP \> 160 mm or DBP \> 100mm
• •10. Severe hypotension: SBP \< 80 mmHg.
• •11. Pregnant or breast-feeding.
• •12. Psychiatric, addictive, or other disorder that compromises patient's ability to provide informed consent, follow study protocol, and adhere to treatment instructions.
• •13. Active cyclosporine use.
• •14. Known allergy or hypersensitivity to FK-506.
• •15. Planned initiation of cardiac or pulmonary rehabilitation during period of study.
• •16. Human Immunodeficiency Virus infection.
• •17. Moderate to severe hepatic dysfunction with a Pugh score \>10.
• •18. Hyperkalemia defined as Potassium \> 5.1 mEq/L at screening .
• •19. Known active infection requiring antibiotic, antifungal, or antiviral therapies.
• •20. Co-morbid conditions that would impair a patient's exercise performance and ability to assess WHO functional class, including but not limited to chronic low-back pain or peripheral musculoskeletal problems.