Joyce M. Evans

Left heart opacification with peripheral venous injection of a new saccharide echo contrast agent in dogs

Opacification of the left heart chambers after venous injection of echo contrast agents with transpulmonary capabilities has been difficult to achieve because of a lack of availability of a biodegradable nontoxic agent that produces uniformly small microbubbles. SHU-508 is a new saccharide echo contrast agent that produces bubble sizes from 2 to 8 microns in diameter, capable of traversing the pulmonary capillary bed and resulting in left heart contrast. The echo intensity produced by this agent was compared with that of agitated saline solution, indocyanine green and SHU-454 (another experimental saccharide agent for right-sided contrast) during 136 injections in eight dogs. Videotaped two-dimensional echographic images were digitized and analyzed with the use of videodensitometry for peak right and left ventricular intensity, pulmonary transit times and time of persistence of contrast. The highest right ventricular intensity value (3,594 +/- 1,393) was achieved with SHU-508 (p less than 0.05 compared with the other agents). The right ventricular contrast seen with SHU-508 also persisted for a longer period (22.8 +/- 12 s) than with the standard agents (p less than 0.001). Left ventricular contrast with SHU-508 was visually evident in all 42 injections, whereas the peak left ventricular intensity was 35% as bright as that produced in the right ventricle by the same agent. Peak left ventricular intensity values from SHU-508 were compared with those from agitated saline solution injected from the pulmonary capillary wedge position in four dogs. SHU-508 produced brighter left ventricular intensity (1,281 +/- 607) compared with that obtained with the saline-wedge technique (p les than 0.002).(ABSTRACT TRUNCATED AT 250 WORDS)

Gait-stance duration as a measure of injury and recovery in the rat sciatic nerve model

The rat sciatic nerve is a well-established animal model for the study of peripheral nerve crush injury. Footprint analysis is the most widely used non-invasive method of measuring functional recovery after injury in this model. However, this method has significant limitations due to inability to obtain clear reproducible prints, especially when the injury is severe, and variation of these prints with gait velocity. In the case of contracture or toe loss, footprint analysis is unreliable. We describe a new technique, gait-stance duration, which is capable of non-invasively quantitating functional recovery in the rat model. This method is not dependent on accurate foot positioning during gait. It utilizes video recording of the animal walking and measures the time each hind foot is in contact with the floor by counting the number of frames that pass. By pairing consecutive steps, it minimizes variation due to changes in velocity and, by calculating a ratio of injured/uninjured hind feet, comparisons to normal gait can be made. This method shows recovery patterns similar to footprint analysis with small inter-animal variability. We believe it has significant advantages over footprint analysis for the measurement of functional recovery in the crushed sciatic nerve rat model.

Enhancement of Functional Recovery Following a Crush Lesion to the Rat Sciatic Nerve by Exposure to Pulsed Electromagnetic Fields

Previous studies showed that exposure to pulsed electromagnetic fields (PEMF) produced a 22% increase in the axonal regeneration rate during the first 6 days after crush injury in the rat sciatic nerve. We used the same injury model to assess the effect on functional recovery. The animals were treated with whole body exposure to PEMF (0.3 mT, repetition rate 2 Hz) for 4 h/day during Days 1-5 while held in plastic restrainers. Functional recovery was serially assessed up to Postinjury Day 43 using recently described video imaging of the 1-5 toe spread and the gait-stance duration. Footprint analysis was also used with calculation of a sciatic function index. Those animals treated with PEMF had improved functional recovery, as compared to sham controls, using the tests for video 1-5 toe spread and gait-stance duration (P = 0.001 and P = 0.081, respectively). This effect was found throughout the 43-day recovery period. No effect was found using the sciatic function index. This study confirms that functional recovery after nerve crush lesion is accelerated by PEMF and has broad implications for the clinical use of these fields in the management of nerve injuries.

Reduction of left ventricular preload by lower body negative pressure alters Doppler transmitral filling patterns

The objective of this study was to evaluate the effect of alterations in preload induced by lower body negative pressure on Doppler transmitral filling patterns. Echocardiograms and Doppler recordings were performed in 18 normal young men (aged 23 to 32 years) during various levels of lower body negative pressure (0, -20 and -50 mm Hg). Lower body negative pressure induced a reduction in diastolic velocity integral (from 12.17 +/- 0.79 to 8.42 +/- 0.71 cm, p = 0.0067) and consequently left ventricular diastolic diameter (from 5.11 +/- 0.09 to 4.45 +/- 0.1 cm, p less than 0.0001). There was a significant reflex increase in heart rate from 59.9 +/- 1.9 to 77.1 +/- 2.4 beats/min (p less than 0.0001), but blood pressure was unchanged. This reduction in preload altered Doppler transmittral filling patterns as follows: 1) peak early velocity (E) decreased from 59.2 +/- 3.8 to 39.1 +/- 1.7 cm/s (p less than 0.0001); 2) atrial filing velocity (A) was unchanged (35.58 +/- 1.5 to 33.52 +/- 1.4 cm/s, p = 0.517); 3) E/A ratio decreased from 1.7 +/- 0.13 to 1.19 +/- 0.08 (p = 0.0087); 4) mean acceleration (from 482 +/- 37 to 390 +/- 27 cm/s2, p = 0.03) and mean deceleration (from 327 +/- 31 to 169 +/- 21 cm/s2, p less than 0.001) of the early filling wave were significantly reduced; and 5) peak acceleration (from 907 +/- 42 to 829 +/- 29 cm/s2) and peak deceleration (from 771 +/- 94 to 547 +/- 76 cm/s2) also decreased, but not significantly.(ABSTRACT TRUNCATED AT 250 WORDS)

A multistage, optimal active contour model

Energy-minimizing active contour models or snakes can be used in many applications such as edge detection, motion tracking, image matching, computer vision, and three-dimensional (3-D) reconstruction. We present a novel snake that is superior both in accuracy and convergence speed over previous snake algorithms. High performance is achieved by using spline representation and dividing the energy-minimization process into multiple stages. The first stage is designed to optimize the convergence speed in order to allow the snake to quickly approach the minimum-energy state. The second stage is devoted to snake refinement and to local minimization of energy, thereby driving the snake to a quasiminimum-energy state. The third stage uses the Bellman (1957) optimality principle to fine-tune the snake to the global minimum-energy state. This three-stage scheme is optimized for both accuracy and speed.

Epinephrine, vasodilation and hemoconcentration in syncopal, healthy men and women

Healthy young people may become syncopal during standing, head up tilt (HUT) or lower body negative pressure (LBNP). To evaluate why this happens we measured hormonal indices of autonomic activity along with arterial pressure (AP), heart rate (HR), stroke volume (SV), cardiac output (CO), total peripheral resistance (TPR) and measures of plasma volume. Three groups of normal volunteers (n = 56) were studied supine, before and during increasing levels of orthostatic stress: slow onset, low level, lower body negative pressure (LBNP) (Group 1), 70 degrees head up tilt (HUT) (Group 2) or rapid onset, high level, LBNP (Group 3). In all groups, syncopal subjects demonstrated a decline in TPR that paralleled the decline in AP over the last 40 s of orthostatic stress. Ten to twenty seconds after the decline in TPR. HR also started to decline but SV increased, resulting in a net increase of CO during the same period. Plasma volume (PV, calculated from change in hematocrit) declined in both syncopal and nonsyncopal subjects to a level commensurate with the stress, i.e. Group 3 > Group 2 > Group 1. The rate of decline of PV, calculated from the change in PV divided by the time of stress, was greater (p < 0.01) in syncopal than in nonsyncopal subjects. When changes in vasoactive hormones were normalized by time of stress, increases in norepinephrine (p < 0.012, Groups 2 and 3) and epinephrine (p < 0.025, Group 2) were greater and increases in plasma renin activity were smaller (p < 0.05, Group 2) in syncopal than in nonsyncopal subjects. We conclude that the presyncopal decline in blood pressure in otherwise healthy young people resulted from declining peripheral resistance associated with plateauing norepinephrine and plasma renin activity, rising epinephrine and rising blood viscosity. The increased hemoconcentration probably reflects increased rate of venous pooling rather than rate of plasma filtration and, together with cardiovascular effects of imbalances in norepinephrine, epinephrine and plasma renin activity may provide afferent information leading to syncope.

False positive head-up tilt:: Hemodynamic and neurohumoral profile

OBJECTIVES This study examined differences in mechanisms of head-up tilt (HUT)-induced syncope between normal controls and patients with neurocardiogenic syncope. BACKGROUND A variable proportion of normal individuals experience syncope during HUT. Differences in the mechanisms of HUT-mediated syncope between this group and patients with neurocardiogenic syncope have not been elucidated. METHODS A 30-min 80 degrees HUT was performed in eight HUT-negative volunteers (Group I), eight HUT-positive volunteers (Group II) and 15 patients with neurocardiogenic syncope. Heart rate and blood pressure (BP) were monitored continuously. Epinephrine and norepinephrine plasma levels, as well as left ventricular dimensions and contractility determined by echocardiography, were measured at baseline and at regular intervals during the test. RESULTS The main findings of this study were the following: 1) All parameters were similar at baseline in the three groups; and 2) During tilt: a) the time to syncope was shorter in Group III than in group II (9.5 +/- 3 vs. 17 +/- 3 min p < 0.05); b) there was an immediate, persisting drop in mean BP in Group III; c) the decrease rate of left ventricular end-diastolic dimensions was greater in Group III than in Group II or Group I (-1.76 +/- 0.42 vs. -0.87 +/- 0.35 and -0.67 +/- 0.29 mm/min, respectively, p < 0.05); d) the leftventricular shortening fraction was greater in Group III than in the other two groups (39 +/- 1 vs. 34 +/- 1 and 32 +/- 1%, respectively, p < 0.05); and e) although the norepinephrine level remained comparable among the groups, there was a significantly higher peak epinephrine level in Group III than in Group II and Group I (112.3 +/- 34 vs. 77.6 +/- 10 and 65 +/- 12 pg/ml, p < 0.05). CONCLUSIONS Mechanisms of syncope during HUT appeared to be different in normal volunteers and patients with neurocardiogenic syncope. In the latter, there was evidence of an impaired vascular resistance response from the beginning of the orthostatic challenge. Furthermore, in the patients there was more rapid peripheral blood pooling, as indicated by the echocardiographic measurements of left ventricular end-diastolic changes, leading to more precocious symptoms. In syncopal patients, the higher level of plasma epinephrine probably mediated the increased cardiac contractility and possibly contributed to the impaired vasoconstrictive response.

Heart rate variability during sympatho-excitatory challenges: Comparison between spontaneous and metronomic breathing

Respiration influences heart rate variability, leading to the suggestion that respiration should be controlled to assess autonomic function by using heart rate variability. Clearly, control of respiration is advantageous or even essential in several experimental circumstances. However, control of respiration, by itself, produces a small, but significant, increase in mean heart rate and a decrease in respiratory synchronous variation in heart rate. We tested whether, in some experimental situations, it may be possible to arrive at similar interpretation about autonomic function with and without using control of respiratory rate. heart rate spectral powers from nine subjects were compared between spontaneous and metronomic breathing during two sympatho-excitatory stresses, lower body negative pressure (LBNP) and head up tilt (HUT). The normalized spectral powers in supine and HUT during spontaneous breathing were: 0.43 and 0.75 in very low (VLF) and 0.28 and 0.09 in high frequency (HF) regions. The powers during metronomic breathing were: 0.36 and 0.82 (VLF) and 0.36 and 0.09 (HF). The powers in supine and LBNP during spontaneous breathing were: 0.43 and 0.81 (VLF) and 0.28 and 0.06 (HF). The powers during metronomic breathing were: 0.36 and 0.80 (VLF) and 0.36 and 0.07 (HF). All p values were <0.05. Therefore, changes in heart rate spectral powers during HUT and LBNP were similar during metronomic breathing and spontaneous breathing. These results suggest that in experimental designs such as in our study, using metronomic breathing may not provide any additional insight into autonomic function than that can be obtained during spontaneous breathing.

Improved footprint analysis using video recording to assess functional recovery following injury to the rat sciatic nerve

Footprint analysis is a non-invasive method to quantitate functional recovery after crush injury in the rat sciatic nerve model. Traditional methods of producing the footprints for measurement are limited by inability to reliably produce clear prints when the injury is severe. We describe the use of video technique with image analysis to record and measure these prints. Video had fewer unmeasurable prints than ink. For the 1-5 and 2-4 toe spreads, there was good correlation of video measurements with ink method and better repeatability using video as compared with ink. However, the print length parameter determined by video had poorer repeatability and poorly correlated with that measured by ink. Therefore, calculation of a Sciatic Function Index by video is not appropriate. Since the print length also varies with gait velocity, we believe that a ratio of injured:uninjured hindfoot 1-5 toe spreads as measured by video is a more reliable and repeatable measure of functional recovery in this model.

Influence of alterations in loading produced by lower body negative pressure on aortic blood flow acceleration.

The objectives of this study were to evaluate the effects of alterations in loading induced by lower body negative pressure on aortic blood flow velocity and acceleration. Twenty-seven normal men were studied during various levels of lower body negative pressure (0 to -60 mm Hg) during which echocardiographic, Doppler and hormonal measurements were obtained. Lower body negative pressure induced a decrease in left ventricular diastolic diameter from 5.18 +/- 0.08 to 4.41 +/- 0.1 cm (p less than 0.0001) and in left ventricular systolic diameter from 3.33 +/- 0.09 to 2.84 +/- 0.1 cm (p less than 0.0001). Shortening fraction remained unchanged. The decrease in diastolic diameter resulted in a reduction in flow velocity integral from 13.8 +/- 0.8 to 7.5 +/- 0.4 cm (p less than 0.0001) and, therefore, in stroke volume from 89.6 +/- 4.7 to 49.5 +/- 2.8 ml (p less than 0.0001). Heart rate reflexly increased from 62.5 +/- 1.9 to 82.2 +/- 2.3 beats/min (p less than 0.0001) as did systemic vascular resistance from 1,280.8 +/- 69.5 to 1,863.4 +/- 121.4 dyne.s.cm-5 (p less than 0.0001). The increase in heart rate was insufficient to maintain cardiac output, which decreased from 5.53 +/- 0.29 to 3.99 +/- 0.21 liters/min (p less than 0.0001). Systolic, diastolic and mean arterial blood pressure was maintained. The negative pressure resulted in a concomitant significant increase in norepinephrine levels from 1.46 +/- 0.09 to 2.056 +/- 0.2 nmol/liter (p = 0.0019) but no change in plasma epinephrine: 0.845 +/- 0.22 to 0.78 +/- 0.11 nmol/liter (p = NS).(ABSTRACT TRUNCATED AT 250 WORDS)