Gary L. Copenhaver

THE RELEASE OF THROMBOXANE A2 AND PROSTACYCLIN FOLLOWING EXPERIMENTAL ACUTE PULMONARY EMBOLISM

The contributions of thromboxane A2 (TXA2) and prostacyclin (PGI2) to the effects of acute pulmonary embolism were evaluated in 18 open-chest rabbits. All rabbits received autologous whole-blood-clot embolus (.4 cc) by way of a catheter in the right ventricle. Pulmonary artery (PA) and left atrial (LA) pressures, and aortic flow (AOQ) were recorded. The stable metabolites of TXA2 (TXB2) and PGI2 (6-Keto PGF1) were assayed by radioimmunoassay at pre- and post-embolization periods (+5, +10, +20, +30, and +40 minutes). Significant elevations of pulmonary vascular resistance (PVR) (normalized), PA pressure, and reduction of AOQ were noted comparing pre-embolus to +5 minute time intervals. A negative correlation was reached between PGI2 and AOQ at +40 minutes (p less than .05). Five of the 13 rabbits died prematurely. At +5 minutes these 5 rabbits had higher PVR (p less than .001) and lower AOQ (p less than .01) than their living counterparts. At +10 minutes AOQ was still significantly lower (p less than .005) and TXB2 was higher (p less than .05) in the premature death group. We conclude that TXB2 is significantly but transiently elevated early following acute pulmonary embolism and may contribute to mortality. In contrast PGI2 does not appear to play an immediate role in the hemodynamic events following embolization but does rise to significant levels later in the course possibly in an attempt to compensate for reduced flow.

Epicardial surface dynamics in the closed-chest normal canine

Past studies of the changing three-dimensional shape of the heart in the closed chest during the cardiac cycle have been restricted to the measurement of local deformations at a relatively few specific locations, and often have required surgical procedures that alter the measurements obtained. In the study reported here, high precision displacement and velocity measurements were obtained at the epicardial interface using a Compton backscatter imaging technique that does not require a surgical intervention or contrast injections. Displacement and velocity measurements were obtained at more than 200 locations at the epicardial interface at 13 ms intervals throughout the cardiac cycle. Measurements of the changing shape of the heart during the cardiac cycle with this technique are precise to 0.1 mm (S.D.). Displacement and velocity patterns recorded in this study confirm and integrate the studies of many others and also add new information. An unexpected vigorous inward motion of both the LV (39 mm s-1) and RV (26 mm s-1) surfaces during isovolumic relaxation and early rapid refill is demonstrated. Velocities during this period equal or exceed those that occur during ejection. During ejection, inward LV motion at the base of the heart precedes that at the apex by 80-90 ms. Posterior LV displacements and velocities during ejection are 4-6 times greater than those at the anterior and apex. The Compton backscatter imaging technique for obtaining undisturbed measurements of cardiac dynamics in the closed chest has potential as a non-invasive clinical tool for serial studies of cardiac surface motion abnormalities. The data presented can also be used to set surface boundary conditions for biomechanical models of heart deformation.

In Vivo Cardiac Muscle Perfusion: A New Measurement Method

A nonradioactive tracer technique for the evaluation of heart disease is presented. A microprocessor controlled scanning system is used to position a germanium detector such that it interrogates an isolated segment of myocardial tissue. Iodine based contrast agent in intravenously injected while irradiating the tissue segment with a low energy X-ray spot beam. X-ray induced iodine fluorescence of the passing contrast agent is then used to monitor the local tissue perfusion.

The Effects of Pacing Site on Left Ventricular Epicardial Surface Velocity Patterns During Systole

Changes in epicardial LV velocity patterns during isovolumic contraction and ejection as induced by ventricular pacing were studied in 15 canines. A noninvasive imaging technique that provided high temporal resolution was used to study the timing of an outward expansion of the LV during isovolumic contraction and the propagation pattern of an inward LV velocity wavefront during ejection. With this technique, surface displacements were measured (± 0.1 mm SD) at 50–70 locations on the LV free wall at 5‐msec intervals. Velocities were calculated by differentiating the surface displacement waveforms and an interpolation procedure was used to provide detailed color coded velocity maps of the LV surface. LV surface velocities were determined from data obtained during closed‐chest endocardial pacing from each of four sites: right atrium, right ventricular apex, left ventricular apex, and right ventricular outflow tract. These surface velocities showed a distinct spatial and temporal pattern for each pacing site. The results show that this noninvasive mapping procedure has potential for determining the location of an ectopic ventricular focus.

Determinants of Decreased Early Ventricular Filling in Man: A Role for External Forces

The determinants of reduced early left ventricular filling and their relative importance were examined in 14 subjects with an ejection fraction > 40%. Simultaneous high‐fidelity left ventricular pressure, mitral annular Doppler velocity recordings, and two‐dimensional echocardiographic data were used. Pressure‐volume curves were created from pressure/echocardiographic/Doppler data and the chamber stiffness constant calculated. The influence of changing filling pressure was examined by studying subjects before and after ventriculography. The ventricular relaxation time constant, chamber stiffness constant, mean right atrial pressure (an index of pericardial restraint and/or ventricular interaction), pulmonary wedge pressure, and heart rate were analyzed for their influence on Doppler filling parameters: isovolumic relaxation time, peak early (E) and atrial (A) filling velocities, and the E/A ratio. The relaxation time constant was the primary determinant of isovolumic relaxation time (r = 0.82, P<0.001). Prolonged relaxation also caused a decrease in the E/A ratio (r=0.73, P<0.001) and early filling. Peak atrial filling velocity and its integral decreased as chamber stiffness rose (P<0.005). Pulmonary wedge pressure had only a modest influence on early filling (r=0.46, P<0.05). Ventriculography did not eliminate the influence of stiffness and relaxation on filling, although it caused early filling and the E/A ratio to rise and isovolumic relaxation time to shorten. Filling became earlier with increasing right atrial pressure and upward pressure‐volume curve shifts. In multivariate regression the E/A ratio was influenced independently by relaxation, filling pressure, right atrial pressure, and chamber stiffness. We conclude that isovolumic relaxation time is a useful measure of ventricular relaxation. However, the E/A ratio is too complex to allow characterization of diastolic function when used alone. Finally, pericardial restraint and/or ventricular interaction during a volume load may confound the relationship between filling pattern and intrinsic ventricular diastolic properties.

Analysis of edge-tracking errors inherent in fluoroscopic images of the beating heart.

RATIONALE AND OBJECTIVES.Because of the complex relationships between the dynamic three-dimensional cardiac surface shape and its projected image, errors arise with the use of two-dimensional silhouettes to measure displacements of the heart. The character and frequency of such errors are examined. METHODS.A high-precision x-ray scatter imaging technique was used to reconstruct the three-dimensional shape of the left ventricular free wall throughout the cardiac cycle. Displacements of the three-dimensional surface were then compared with those on the two-dimensional projected silhouette. Silhouette displacement errors were determined as a function of time during the cardiac cycle and variability between hearts. RESULTS.Differences between silhouette measurements and those on the cardiac surface range from 0% to 125% of peakto- peak displacements occur, along 33% to 75% of the silhouette contours and cover 66% of the cardiac cycle. CONCLUSION.Two-dimensional silhouette displacements provide inconsistent measurements of motion patterns on the three-dimensional cardiac surface.

The Measurement of Ventricular Wall Thickening Using Scattered and Fluorescence Radiation

A new technique for the simultaneous measurement of left ventricular epicardial and endocardial wall dynamics is presented. X-rays scattered from the surface of the heart are used to monitor motion at the epicardial surface and iodine fluorescence induced in the blood pool is used to monitor motion of the endocardium. Continuous wall thickness measurements throughout the cardiac cycle are obtained.