Hani N. Sabbah

Measured Turbulence and Its Effect on Thrombus Formation

Turbulence is one of the hydraulic disturbances implicated in thrombus formation, even though absolute proof of its contributory effect is lacking. Because of the importance of a possible effect of turbulence on thrombus formation, the relation was studied in eight dogs. In each dog, two arteriovenous shunts were established, one from each femoral artery to the contralateral femoral vein. Only one shunt contained a turbulence-producing device; otherwise, the shunts were identical in shape, size, and material. The intensity of turbulence distal to the turbulence generator was quantified in vitro by measuring the relative magnitude of the randomly fluctuating velocities. In each of the eight dogs, more thrombi, by weight, accumulated in the turbulent shunt than in the laminar shunt (P < 0.001). Thrombi from the turbulent shunt weighed 180 ± 30 (SE) mg, whereas those from the laminar shunt weighed 0.9 ± 0.6 mg. The weight of thrombi that accumulated within the turbulent system appeared to be related to the intensity of turbulence. A linear relation was observed between the Reynolds number in the region of the turbulence-producing orifice and the weight of the thrombi within the turbulent shunt (r = 0.90). The relative intensity and the absolute intensity of turbulence distal to the turbulence generator were also linearly related to the Reynolds number (r = 0.97 and 0.90, respectively). The results of this study therefore indicate that turbulence is a characteristic of blood flow that can contribute to the formation of thrombi.

Turbulent blood flow in the ascending aorta of humans with normal and diseased aortic valves.

Turbulent Mood flow may contribute to a variety of pathophysiological effects. Because of its postulated importance, this study was undertaken to determine whether turbulent flow does in fact occur in the human body. In 15 persons (seven normal, seven aortic valvular disease, one prosthetic aortic valve), point velocity was measured in the ascending aorta with a hot-film anemometer probe. In one normal individual with a high cardiac output, turbulent flow occurred above the aortic valve during peak flow which corresponded to a peak Reynolds number of 10,000. In toe other six normal subjects (peak Reynolds numben of 5,700-8,900), flow was highly disturbed during peak ejection. Each of the subjects with aortic valvular disease and the subject with a prosthetic aortic valve showed turbulent flow during nearly the entire period of ejection, with Fourier components of velocity of significant magnitude up to 320 Hz (the maximum frequency we could evaluate with the equipment available). The turbulence energy density was higher in subjects with abnormal valves (3.2-14.6 ergs/cm), than in normal subjects (0.6-2.9 ergs/cm1). In subjects with aortic stenosis, turbulence was observed throughout the ascending aorta and in the innominate artery. In others, the turbulence dissipated more proximally. The results of this study indicate that turbulent flow can occur in the as cending aorta of subjects with normal cardiac function; and it occurs consistently in the ascending aorta of individuals with abnormal aor tic valves.

Continuing disease process of calcific aortic stenosis. Role of microthrombi and turbulent flow.

Microthrombi with evidence of organization were observed in 10 of 19 calcified and stenotic aortic valves (53 percent). The organization that results from such thrombi may contribute to the deformity of the valve. Repetitive deposits of microthrombi, followed by organization and calcification, would explain the continuous process of stenosis in previously deformed aortic valves. The formation of such thrombi may be initiated by turbulent flow and other fluid dynamic factors.

Turbulent blood flow in humans: its primary role in the production of ejection murmurs.

To clarify the postulate that turbulence may produce ejection murmurs, point velocity and sound were measured in the ascending aorta of 13 subjects: six with normal aortic valves, six with aortic valvular disease, and one with a Björk-Shiley prosthetic aortic valve. Velocity was measured with a catheter-tip hot film anemometer probe, and sound was measured with a catheter-tip micromanome-ter. Ejection murmurs detected intra-arterially were always found to be associated with turbulent or highly disturbed flow. Conversely, in the absence of intra-arterial sound during ejection, only minor disturbances of flow were detected. A linear relation between the sound energy density and turbulent energy density was shown (r = 0.92) and a linear relation between the acoustic power output (sound intensity) and turbulent power supply (r = 0.87) also was shown. Studies in vitro of sound and point velocity distal to a porcine valve inserted within a cast of the aorta, which permitted precise centering of the transducers along the axis of flow, confirmed these observations. When the power generated by the turbulence exceeded 3 ergs/sec per cm2, the murmurs were audible at the chest wall. The clinical gradation of the intensity of the murmurs increased as the power of turbulence increased. In conclusion, in this study we have demonstrated a clear association between turbulent blood flow and systolic ejection murmurs.

Investigation of the theory and mechanism of the origin of the second heart sound.

To investigate further the origin of the second heart sound we studied human subjects, dogs, and a model in vitro of the cardiovascular system. Infra-arterial sound, pressure, and, where possible, flow and nigh speed cine (2,000 frames/sec) were utilized. The closure sound of the semilunar valves was of higher amplitude in the ventricles than in their respective arterial cavities. The direction of inscription of the main components of intra-arterial sound were opposite in direction to the components of intraventricular sound. Notches, representative of pressure increments, were noted on the ventricular pressure tracings and were coincident with the components of sound. The amplitude of the closure sound varied with diastolic pressure, but remained unchanged with augmentation of forward and retrograde aortic flow. Ones showed second sound to begin after complete valvular dosure, and average leaflet closure rate was constant regardless of pressure. Hence, the semilunar valves, when closed, act as in elastic membrane and, when set into motion, generate compression and expansion of the blood, producing transient pressure changes indicative of sound. The magnitude of the initial stretch is related to the differential pressure between the arterial and ventricular chambers. Sound transients which follow the major components of the second sound appear to be caused by the continuing stretch and recoil of the leaflets. Clinically unexplained findings such as the reduced or absent second sound in calcific aortic stenosis and its paradoxical presence in congenital aortic stenosis may be explained by those observations.

Force-velocity-length relations in man expressed by a single hemodynamic expression: The ejection rate of change of power at peak tension

An attempt was made to develop a hemodynamic indicator of pump function that relates to the contractile characteristics of cardiac muscle. The ejection rate of change of power has ideal characteristics for this purpose. It is firmly based upon theories of fluid dynamics and its derivation is free of assumptions related to heart structure and function. It is measured as p dQ/dt + Q dp/dt, where p = pressure and Q = flow. When measured at peak tension, the ejection rate of change of power was (12.3 +/- 0.8) X 10(8) dynes cm sec-2 in 11 patients with abnormal ventricular performance (P less than 0.001). Studies in dogs showed no effect of preload or afterload. This suggests a relation to characteristics of muscle fibers, which was shown. If one assumes a thin wall sphere, the ejection rate of change of power at peak tension reduces to the following function of tension (T), fiber length (2 pi r), and rate of shortening (2 pi dr/dt): d(power)/dt = 8 pi T](dr/dt)2 + r d2r/dt2[. Thus, the contractile characteristics of muscle fibers (force, velocity and tension) are related in an uncomplicated fashion by a single and highly discriminating hemodynamic indicator of ventricular performance, the ejection rate of change of ventricular power measured at peak tension.

Effect of turbulent blood flow on systolic pressure contour in the ventricles and great vessels: Significance related to anacrotic and bisferious pulses

The effect of turbulent blood flow on the contour of systolic pressure in the left and right ventricles and great vessels was investigated in 64 patients undergoing diagnostic cardiac catheterization. Intracardiac pressure and sound were recorded using a catheter-tip micromanometer. Measurements were made in normal subjects and patients with a variety of disorders including aortic stenosis, hypertrophic obstructive cardiomyopathy, coarctation of the aorta and atrial septal defect. Observations showed a consistent association of the intracardiac murmur, which is indicative of turbulence, with a transient reduction of the centrally recorded systolic pressure. The resultant abnormal systolic pressure contour can be explained on the basis of fluid dynamic considerations related to turbulence.

Isovolumic fractional rate of change of power: Its applicability to assessment of ventricular performance in patients

The ratio of the instantaneous isovolumic rate of change of power, normalized to instantaneous isovolumic power, appears to be an expression of physiologic and practical significance. This ratio, termed the isovolumic fractional rate of change of power, describes the capability of the ventricle to sustain, during isovolumic contraction, an acceleration of energy production relative to instantaneous rates of energy production. The expression is independent of assumptions of ventricular geometry, fiber orientation, symmetry of contraction or elasticity of muscle fibers. It was derived upon the basis of established principles of fluid dynamics. The expression serves in an integrative fashion by demonstrating a simple relation between characteristics of performance derived on the basis of fluid dynamics and those derived on the basis of muscle mechanics. In this study, the isovolumic fractional rate of change of power permitted distinction between patients with normal and abnormal ventricular performance (as characterized by the ejection fraction, mean velocity of circumferential fiber shortening and end-diastolic volume index) (P less than 0.01). The firm theoretical basis of the isovolumic fractional rate of change of power, and its demonstrated capability to permit identification of patients with normal or abnormal left ventricular performance, recommends it as a meaningful and useful hemodynamic expression.

Hemodynamic effects of petrinitrol in man

The hemodynamic effects of petrinitrol, a new antianginal agent, were evaluated in 30 patients during cardiac catheterization. The administration of 5 mg and 10 mg doses, both sublingually and orally, caused significant reductions of systemic arterial pressure, cardiac index, stroke index, and pulmonary arterial pressure that were prominent 15 to 30 minutes after administration of the drug. All but the 5 mg oral dose produced an increment of heart rate. The 10 mg sublingual dose also caused a significant reduction of left ventricular work. Total systemic resistance, and the product of blood pressure and heart rate did not change significantly. It appears that petrinitrol and nitroglycerin have several similar effects upon the cardiovascular system; but in the doses administered, petrinitrol caused changes of greater magnitude and longer duration.