We used a pulsed Doppler technique to examine the flow velocity pattern in the right ventricular outflow tract in 33 adults. In the patients with normal pulmonary artery pressure (mean pressure < 20 mm Hg, 16 patients), ejection flow reached a peak level at midsystole (137 + 24 msec, mean + SD), producing a domelike contour of the flow velocity pattern during systole. In contrast, the flow velocity pattern in patients with pulmonary hypertension (mean pressure ¢ 20 mm Hg,17 patients) was demonstrated to accelerate rapidly and to reach a peak level sooner (97 + 20 msec, p < .01); in 10 of the pulmonary hypertensive patients a secondary slower rise in flow velocity was observed during a deceleration, resulting in the midsystolic notching. The time to peak flow (acceleration time, AcT) and right ventricular ejection time (RVET) were measured from the flow velocity pattern. Either AcT or AcT/RVET decreased with increase in mean pulmonary artery pressure, and a very high correlation (r = -.90) was found between AcT/RVET and log,0 (mean pulmonary artery pressure). The use of this technique permitted the noninvasive estimation of the pulmonary artery pressure. Circulation 68, No. 2, 302-309, 1983. NONINVASIVE evaluation of pulmonary hypertension has been an important clinical problem for many years. The presence of pulmonary hypertension has been assessed by abnormalities in heart sounds,' in electrocardiographic tracings, or in chest x-rays,2 but to date, the accurate measurement of the pulmonary artery pressure requires the use of cardiac catheterization procedures. The development of echocardiographic techniques has allowed the investigation of pulmonic valve motion,3 which represents some characteristic abnormalities associated with pulmonary hypertension, such as rapid opening slope in systole,j5 attenuation or absence of the "a" dip,' prolongation of the ratio of right ventricular preejection period (RPEP) to right ventricular ejection time (RVET),57 and midsystolic semiclosure of pulmonic valve.)6 A recent experimental study8 emphasized that these abnormalities of the pulmonic valve motion were determined by abnormal flow changes in the pulmonary artery. However, flow characteristics with regard to pulmonary artery pressure either in the pulmonary artery or in the right ventricular outflow tract have not been successfully studied in man. Our objectives were to study the blood flow characteristics in the right ventricular outflow tract in patients with pulmonary hypertension by a pulsed Doppler technique9-I and to develop an index that would permit quantitative evaluation of pulmonary hypertension by noninvasive methods. Materials and methodsPatient selection. Thirty-eight patients admitted for diagnostic catheterization were examined by a pulsed Doppler technique. Five patients were excluded in whom Doppler recordings of flow velocity in the right ventricular outflow tract were not satisfactorily obtained because of poor penetration of ultrasound through the chest wall. Doppler examination was perfor...

To elucidate the role of loading sequence in afterload-dependent slowed relaxation in hearts in situ, the time constants (Texp from best exponential fitting method and TL from semilogarithmic method) of isovolumetric left ventricular (LV) pressure decay were studied in nine anesthetized open-chest dogs under the pharmacological blockade of autonomic nerve activity. An afterload change was imposed by clamping the ascending or descending aorta to make the peak LV pressure early or late in systole. During afterload interventions, in contractions with the peak LV pressure in late systole Texp and TL were significantly (P less than 0.05) larger than in those with the peak LV pressure in early systole in any comparable peak LV pressure range. Moreover, both time constants were directly correlated (P less than 0.01) with the time of peak LV pressure irrespective of peak LV pressure and clamp mode of aorta. In another protocol, marked differences both in Texp and TL were also observed between each of 25 pairs of contractions with different loading sequence but with comparable peak LV pressure and LV dimension (segment length). Thus afterload-dependent slowed relaxation in hearts in situ could not be attributed to an increased total load but to the altered loading sequence associated with an increase in afterload.

SUMMARY We studied the effect of systolic pressure and volume changes on the end-systolic pressure at a fixed end-systolic volume in the left ventricle of excised, cross-circulated canine hearts. Instantaneous ventricular volume was controlled and both end-diastolic and end-systolic volumes were clamped, as preprogrammed by a volume servo pump system. Ventricular ejection was completed at the end of natural systole. When the onset and velocity of ejection were widely varied during contractions with a given set of end-diastolic and end-systolic volumes, the end-systolic pressure was little affected by the changes in the systolic pressure and volume under a stable contractile state. When the end-diastolic volume was increased from the isovolumic condition, the end-systolic pressure at the same end-systolic volume decreased (P < 0.05) from the peak isovolumic pressure by 5-14%, for an ejection fraction of 40-70%. When the end-systolic volume was decreased while the end-diastolic volume was fixed, the end-systolic pressure decreased in proportion to end-systolic volume. These results were interpreted to indicate that, when ejection ends at the end of systole, stroke volume of the ventricle with a given end-diastolic volume is determined predominantly by the end-systolic pressure rather than by the entire systolic courses of the pressure and volume, drc Res 44; 238-249, 1979 AFTERLOAD, preload, and contractility are major determinants of the stroke volume of the ventricle (Bishop et al, 1976;Parmley et al., 1977) and the amount of shortening of cardiac muscle (Braunwald et al., 1976). In most experiments on cardiac muscle, afterload is an isotonic force rather than a timevarying force, and the constant after load force determines instantaneous shortening velocity and the amount of shortening (Braunwald et al., 1976). In recent experiments on ventricles, afterload pressure (Weber et al., 1974) and even ventricular wall force (Burns et al., 1973) were kept constant at various levels, and either the constant pressure or force afterload was a major determinant of stroke volume (Weber et al., 1974;Burns et al., 1973). More recently, instantaneous time-varying arterial pressure and ventricular wall force throughout systole (both of which are determined as a result of the complex interaction of the ventricle with the arterial impedance) have been considered to affect

We studied diastolic stiffness of 10 coronary-perfused twitching papillary muscles of the canine right ventricle. The muscle beat at a regular sinus rhythm of 122 +/- 20 (SD) beats/min at 37 degrees C. They were stretched slowly at a constant rate. Diastolic force increased exponentially with the stretch. Calculating Lagrangian stress (sigma) and strain (epsilon) from diastolic force and length, we found a linear relationship between ln sigma and epsilon within the physiological range of strain (0.025 less than epsilon less than 0.4). This indicates that the diastolic stress-strain relationship of the canine papillary muscle can be approximated by a single exponential curve: sigma = a.exp(b.epsilon). The mean +/- SD of the stiffness constant b was 18.0 +/- 3.2 (dimensionless). Our b values are comparable to those of dogs and human subjects, either indirectly assessed from the ventricular pressure-volume relationship or directly obtained in excised quiescent muscle specimens. Different coronary perfusion pressures (75-125 mmHg) in 10 muscles showed a statistically significant positive correlation to b values.

A 25-year-old woman with neurofibromatosis was admitted to our hospital for evaluation of hypertension. When she was 6 years old, she was diagnosed as having neurofibromatosis and XXX syndrome because of multiple café-au-lait spots, neurofibromas of the skin and mental retardation. Chromosome analysis revealed that her karyotype was 46, XX/47, XXX. Renal arteriography disclosed aneurysmal change and stenosis of the right renal artery. After right-side nephrectomy and aneurysmectomy, the kidney was autotransplanted in the left iliac fossa. Surgical procedure resulted in marked amelioration of the hypertension without medical treatment. Thus, aortorenal bypass and renal autotransplantation have emerged as the preferred revascularization operations. This is the first report of a chromosomal linkage between neurofibromatosis which is thought to be an autosomal dominant disease and the XXX syndrome.