Pulmonary hypertension and its sequelae of cor pulmonale and right ventricular (RV) failure may be complications of many diseases of the lung and chest wall. Diagnosis of pulmonary hypertension by physical examination, chest radiograph, EKG, or other non-invasive methods is very difficult, and most cases are not discovered until late in the course of the illness. At present, right heart catheterization remains the only definitive technic for the measurement of pulmonary arterial (PA) pressures and right heart function. This is an invasive procedure not suitable for screening or routine follow-up. In previous studies, we have employed radionuclide scanning of the heart and lungs to estimate PA pressure and assess RV function non-invasively. We have shown that postural shifts in the distribution of pulmonary blood flow measured with Tc-99m macroaggregated albumen can predict PA pressure. Also, we have demonstrated that standard Tc-99m gated blood pool scans of the right heart do not accurately reflect data obtained during right heart angiography, principally because of interfering radioactivity from the left heart. We propose to use the short-lived isotape Krypton (Kr)-81m (Tau 1/2 = 13s.) to develop a non-invasive technic for the assessment of PA pressure and the evaluation of RV performance. Kr-81m is an inert gas with excellent imaging qualities and low radiation dosimetry. It is exhaled during its initial transit through the lung, never reaching the left heart, and thus permitting selective imaging of the right heart. We have developed a technic for the preparation and intravenous delivery of sterile Kr-81m solution and received F.D.A. approval for its use (IND #10800). This project will derive indices of RV Function from gated images of the heart. Computer programs will be written for automated analysis of scan data to improve reliability and reproducibility. These data will be compared with clinical and right heart catheterization data in a canine model of pulmonary hypertension as well as from patients with pulmonary hypertension. We will determine which scan parameters best reflect the hemodynamic response of the pulmonary circulation. Such technics should permit investigations to define the pathophysiology and effect of therapeutic interventions in cardiopulmonary conditions associated with pulmonary hypertension and/or right ventricular dysfunction.
