Paul D. Stein

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.

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.

Pathophysiology of the Pulmonary Circulation in Emphysema Associated with Alpha1 Antitrypsin Deficiency

Patients with homozygous alpha1 antitrypsin deficiency present a unique opportunity for evaluation of the pulmonary vasculature in primary emphysema. In five patients, the detailed angiographic appearance of small (0.2-2.0 mm diameter) muscular pulmonary arteries, shown by wedge arteriography, was correlated with the results of right heart catheterization during the control hypoxemic state (average arterial Po2 50 mm Hg), the administration of oxygen (average arterial Po2 90 mm Hg), and a constant infusion of aminophylline. In all patients, wedge arteriograms in the lower zones of the lungs showed a sparsity of arborization and a diminished background blush of capillary filling. These abnormalities were in the areas of diminished pulmonary blood flow, as indicated by the pulmonary scintiscans and the capillary phase of pulmonary arteriograms. The administration of oxygen and of aminophylline produced an increase in the diameter of arteries 0.5 to 2 mm in diameter on the wedge arteriograms of some of the patients. The average pulmonary arterial mean pressure, 30 mm Hg, and average pulmonary vascular resistance, 300 dyne-sec-cm−5, were both elevated during the control hypoxemic state and decreased in each patient during the administration of oxygen and of aminophylline. This study demonstrates abnormalities of the small pulmonary arteries in patients with alpha1 antitrypsin deficiency. These abnormalities may be responsible for pulmonary hypertension and altered regional perfusion.

New Functional Concept of Valvular Mechanics in Normal and Diseased Aortic Valves

The orifice area of the functioning aortic valve was measured roentgenographically and related to flow across the valve in 27 patients (12 with normal valves). The orifice area of normal valves was linearly related to stroke index and to left ventricular ejection rate. Less than half of the cross-sectional area of the valve was utilized in most patients during the resting state. A larger percentage of the anatomical cross-sectional area was utilized during states of higher flow. Cinematographic studies of porcine valves in vitro showed a comparable flow-dependent orifice size. These results suggest the concept of a functional or physiologic cross-sectional area of the aortic valvular orifice. The anatomic cross-sectional area may be restricted without impingement upon the functional cross-sectional area in states in which flow across the valve is low.

Aortic Insufficiency in Ehlers-Danlos Syndrome

A patient with Ehlers-Danlos syndrome (hypermobility of the joints, and hyperelasticity and fragility of the skin) associated with aortic regurgitation is reported. The aortic regurgitation appeared to be due to a combination of dilatation of the aortic ring and enlargement of the sinuses of Valsalva. Ehlers- Danlos syndrome is a rare cause of aortic regurgitation which occasionally, as in this patient, may be of clinical importance.

Velocity and flow measurements by electromagnetic techniques

Abstract In this review of electromagnetic flowmetry, cardiovascular applications of velocity and flow measurements in patients are emphasized. The theory of electromagnetic flowmeters and sequential developments in the field are surveyed in relation to practical problems of utilization of electromagnetic flow devices. The distinction between catheter-tip velocity transducers and catheter flow transducers is discussed. A variety of electromagnetic catheter-tip devices are described, and their potential applicability to patient care is considered.

Velocity of coronary sinus blood flow as an indicator of coronary arterial flow

Abstract In order to determine the validity of coronary sinus mean blood velocity as an indicator of coronary arterial mean blood flow, comparisons were made of the effects of various interventions upon coronary sinus velocity and left anterior descending coronary arterial flow. Velocity in the coronary sinus was measured with a cathetertip electromagnetic transducer. Flow in the left anterior descending coronary artery was measured simultaneously with a cuff electromagnetic flow transducer. Forty-two observations of the effects of norepinephrine, isoproterenol, and asphyxia were made in seven dogs under pentobarbital anesthesia. Coronary sinus mean velocity increased nearly in direct proportion to increments of left anterior descending mean flow following norepinephrine, isoproterenol, and asphyxia. As would be expected, increments in coronary sinus velocity were linearly related, but were smaller than the increments in left anterior descending flow during reactive hyperemia of the left anterior descending coronary artery. Coronary sinus velocity qualitatively reflected changes of left anterior descending flow, but did not reliably quantitate these changes following nitroglycerin. The results of this study indicate that coronary sinus blood velocity is a fairly reliable indicator of changes of coronary arterial flow. It can be utilized under rapidly changing conditions and monitored continuously over long periods. The method requires no major surgery and would seem to be potentially applicable to human subjects.

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.