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Biomedical subjects

W L Henry

Publications and source records attributed to W L Henry.

At least 37 records · Page 2Linked to original sources

Assessment of normal and atherosclerotic arterial wall thickness with an intravascular ultrasound imaging catheter.

A prototype intravascular ultrasound imaging catheter with a 20 MHz transducer was used to obtain 59 cross-sectional images in 14 segments of human atherosclerotic arteries. Three distinct components of the arterial wall were visualized on the ultrasound images: a highly reflective intima, an echolucent media, and a moderately reflective adventitia. Images were obtained at 1 mm increments in vitro and were compared with histologic sections at the same levels. Measurements of the arterial layers showed a close correlation between ultrasound images and histologic sections for the thickness of the intimal plaque (r = 0.91), the media (r = 0.83), and the total wall thickness (r = 0.85). The ultrasound images overestimated the mean intimal and total wall thickness by 0.3 mm and 0.7 mm compared to measurements in histologic sections (p less than 0.001). Intravascular imaging with high-frequency ultrasound is an accurate method for measuring microanatomic arterial dimensions and the extent of atheromatous involvement of the arterial wall. This method could represent an important adjunct to traditional angiographic techniques for assessing the severity of atherosclerosis.

Arteries↗

Pitfalls in the display of color Doppler jet areas: combined variability due to Doppler angle, frame rate, and scanning direction.

UNLABELLED: The Doppler color jet area depicting a regurgitant or shunt lesion may be useful in estimating its severity. However, color jet area may be affected by technical factors. We studied the combined effects of Doppler angle, frame rate, and scanning direction on the Doppler color jet area of a free jet with 10-mL injection. RESULTS: (1) Angle effects: color flow area was 11.7 +/- 2.0 cm2 at a Doppler angle of 20 degrees , and 2.3 +/- 1.2 cm2 at an angle of 60 degrees , when other parameters were kept constant (frame rate = 12 frames/sec, reverse scanning direction). (2) Frame rate effects: with other parameters kept constant (Doppler angle = 20 degrees , reverse scanning direction), color flow area was 11.7 +/- 2.0 cm2 at a rate of 12 frames/sec and 6.5 +/- 1.8 cm2 at 6 frames/sec. (3) Scanning direction effects: with other parameters kept constant (Doppler angle = 20 degrees , frame rate = 9 frames/sec), color flow area was 7.3 +/- 1.1 cm2 with scanning in the reverse direction, and 20.5 +/- 1.6 cm2 with scanning in the forward direction. (4) Combined effects: In our in vitro studies, the maximum color flow area was 20.5 +/- 1.6 cm2, and the minimum area was 1.5 +/- 0.2 cm2 (nearly twelve-fold). CONCLUSIONS: Doppler color jet area correlated inversely with Doppler angle (P less than 0.01) and directly with frame rate (P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Echocardiography, Doppler↗

Intravascular ultrasonic imaging.

Because conventional imaging methods are inadequate for evaluating human coronary arteries in vivo, an intravascular ultrasonic imaging catheter was developed that allows the arterial wall to be studied in cross-section from within the artery. The catheter incorporates a mechanically rotating 20-MHz transducer, which is designed so that the ringdown occurs within the catheter and imaging is permitted up to the catheter's surface. The device rotates at 1800-rpm within a plastic sleeve and provides real-time cross-sectional images at 30 frames/sec. Preliminary experimental and clinical studies indicate that the intravascular ultrasonic imaging catheter could play a valuable role in providing preoperative information concerning arterial wall thickness and tissue characteristics, in distinguishing normal from diseased arterial wall structures during therapeutic intervention, and in assessing the results of intervention.

Journal Article↗

Regulation of macrophage physiology by L-arginine: role of the oxidative L-arginine deiminase pathway.

The L-arginine content of the extracellular fluid in sites of predominant macrophage infiltration is reduced below plasma levels due to the activity of macrophage-derived arginase. Investigation of the effects of altered L-arginine availability on macrophage physiology reveals that culture of rat peritoneal macrophages in media containing L-arginine in the concentrations present in inflammatory lesions (less than 0.1 mM) enhances activation-associated functions. In contrast, culture in the higher L-arginine concentrations found in standard tissue culture media (0.4 to 1.2 mM) suppresses most macrophage functions (superoxide production, phagocytosis, and protein synthesis). An exception is the tumor cytotoxicity of Corynebacterium parvum-elicited macrophages which is enhanced by culture in supraphysiologic concentrations of L-arginine. Work reported here investigated the mechanisms for these L-arginine-dependent effects and, more specifically, the role of the recently described oxidative L-arginine deiminase pathway in the regulation of macrophage physiology. Overnight culture of resident or C. parvum-elicited peritoneal macrophages in media containing increasing concentrations of L-arginine (6 microM to 1 mM) resulted in: inhibition of electron transport chain activity (resident and C. parvum-elicited macrophages), increased lactate production (resident macrophages), and decreased ATP content (resident and C. parvum-elicited macrophages). In line with these findings, viability was markedly decreased after 2 days of culture when the initial L-arginine concentration was greater than or equal to 0.1 mM. As shown before, increasing media concentrations of L-arginine were associated with suppression of superoxide production and cytotoxicity in resident macrophages, and with reduced superoxide production and increased cytotoxicity in C. parvum-elicited macrophages. All L-arginine-dependent metabolic and functional alterations, as well as the loss of viability, were prevented by NG-monomethyl-L-arginine, a specific inhibitor of the oxidative L-arginine deiminase pathway. These results demonstrate that flux of L-arginine through the oxidative L-arginine deiminase pathway results in the inhibition of oxidative metabolism in rat macrophages. This metabolic inhibition may, through alterations in the macrophage high energy phosphate stores, mediate the suppression of cell functions and result ultimately in cell death.

Animals↗

Factors determining maintenance of sinus rhythm after chronic atrial fibrillation with left atrial dilatation.

Successful therapy of atrial fibrillation (AF) has been reportedly influenced by a variety of factors including patient age, type of underlying heart disease, duration of arrhythmia, left ventricular function and left atrial (LA) size. To determine which of these factors are associated with maintenance of sinus rhythm after conversion, 43 patients with symptomatic chronic AF in the setting of a dilated left atrium (greater than or equal to 45 mm, range 45 to 78) were followed for at least 6 months after the return of sinus rhythm. Class IA drugs, IC drugs or amiodarone were used for therapy. Life table analysis showed sinus rhythm to be maintained in 81% for 6 months, 79% for 12 months and 60% for 24 months. Factors positively associated with success were conversion with drug therapy alone, duration of chronic AF less than or equal to 1 year, absence of mitral valve disease and LA dimension less than or equal to 60 mm (all p less than 0.05). Patient age, left ventricular function and presence of coronary disease were not associated with outcome. Thus, patients with moderate LA dilatation (45 to 60 mm) and a short duration of chronic AF can often be maintained in sinus rhythm, especially if they convert with pharmacologic intervention alone.

Aged↗

Regulation of macrophage functions by L-arginine.

Sites of inflammation with prominent macrophage infiltration, such as wounds and certain tumors, are uniquely deficient in free arginine. The effects of arginine availability on macrophage physiology were investigated. When cultured in media containing less than 0.1 mM L-arginine, rat resident peritoneal macrophages exhibited enhanced spreading, tumor cytotoxicity, superoxide production, phagocytosis, and protein synthesis. Thus, arginine concentrations similar to those found in sites of inflammation can augment macrophage functions, while those found in plasma (approximately 0.1 mM) and in commonly used culture media (0.4 to 1.2 mM) are inhibitory. Culture in homoarginine, but not D-arginine, ornithine, citrulline, urea, histidine, or lysine also inhibited macrophage tumor cytotoxicity, indicating the specificity of the effect. In contrast to resident macrophages, the tumor cytotoxicity of peritoneal macrophages obtained after C. parvum injection was suppressed by culture in arginine-deficient media. However, L-arginine-deficient media enhanced all other activation-associated functions in C. parvum-elicited macrophages as in resident cells. Arginine-free wound fluid promoted resident macrophage tumoricidal activity when compared with rat serum, and again, the addition of L-arginine was inhibitory. The marked effects of L-arginine availability on macrophage functions, together with the knowledge that these cells modify the extracellular arginine concentration in sites of inflammation through arginase, provide evidence for an autoregulatory mechanism of macrophage activation.

Animals↗

Antiarrhythmic efficacy of solitary beta-adrenergic blockade for patients with sustained ventricular tachyarrhythmias.

To assess the efficacy and predictability of solitary beta-adrenergic blocker (BB) therapy for ventricular tachyarrhythmia (VT), 30 patients (16 men and 14 women) with a mean age of 55 years, who initially had sustained ventricular tachycardia (70%) or ventricular fibrillation (30%), were studied. Results of baseline arrhythmia tests showed VT on ECG monitoring in 57% of the patients, during exercise in 50%, induced by programmed stimulation in 69%, increasing to 86% during isoproterenol. BB therapy prevented inducible VT during programmed stimulation in 37% of the patients, prevented VT on ECG monitoring in 54%, and prevented VT during exercise in 83%. Long-term BB therapy was given to 24 of 30 patients, whereas six other patients with hemodynamically unstable VT during BB therapy received other long-term treatment. During a mean follow-up of 824 days, 6 of 24 patients had recurrent VT. BB therapy was discontinued in two patients because of side effects. Long-term success was predicted by left ventricular ejection fraction greater than 45%, absence of coronary disease, and age less than 60 years (all p less than 0.02). Neither suppression of arrhythmia during exercise testing, nor results of programmed stimulation or ECG monitoring were predictive of outcome. Thus beta-adrenergic blockers can be effective as solitary antiarrhythmic therapy in selected patients with VT.

Adrenergic beta-Antagonists↗

Intravascular ultrasound cross-sectional arterial imaging before and after balloon angioplasty in vitro.

A prototype ultrasound imaging catheter was evaluated in vitro using 17 human atherosclerotic artery segments before and after balloon dilatation angioplasty. The catheter was 1.2 mm in diameter and incorporated a single 20-MHz ultrasound transducer to obtain cross-sectional images of the arterial lumen. In 15 of the 17 (88%) arteries, high quality images were obtained, which demonstrated clear demarcation between the lumen and the endothelium, the atheroma plaque, the muscular media, and the adventitia. Qualitative characteristics of plaque disruption, dissection, and residual flaps were readily visible. In addition, quantitative information about cross-sectional lumen area was obtained before and after balloon dilatation. The mean cross-sectional lumen area increased from 8.7 to 15.1 mm2 (p less than 0.01) following balloon dilatation. The lumen area measured from the ultrasound images following dilatation correlated closely with the area measured from histologic sections (r = 0.88). The results from this study indicate that a small-diameter ultrasound imaging catheter can be developed that will provide high-resolution qualitative and quantitative information during peripheral and coronary angioplasty.

Angioplasty, Balloon↗

Evaluation of age, gender, heart rate and blood pressure changes and exercise conditioning on Doppler measured aortic blood flow acceleration and velocity during upright treadmill testing.

To evaluate the effect of upright exercise on aortic peak flow acceleration and velocity, 60 normal subjects between 15 and 74 years of age were evaluated by continuous wave Doppler during treadmill stress testing using the Bruce protocol. Subjects were divided into 3 age groups, each with 20 subjects: group 1, 21 +/- 4 years of age (mean +/- standard deviation), group 2, 36 +/- 5 years and group 3, 58 +/- 7 years. Periodic measurements of heart rate, blood pressure and Doppler blood flow velocity and acceleration were made before, during and after exercise. Continuous wave Doppler measurements were recorded from the suprasternal notch. The relation between Doppler aortic measurements and age, gender, normal heart rate and blood pressure responses during exercise, and exercise preconditioning, was evaluated. Age alone was significantly related (inversely) to immediate postexercise Doppler aortic peak blood flow peak acceleration (group 1, 55 +/- 15, group 2, 46 +/- 11 and group 3, 36 +/- 9 m/s2, p less than 0.05) and peak velocity (1.1 +/- 0.2, 1.0 +/- 0.2 and 0.8 +/- 0.2 m/s, respectively, p less than 0.01). Gender, heart rate and blood pressure changes during exercise, as well as preconditioning, had no significant effect on these flow characteristics. Consequently, the effects of normal aging must be considered when using Doppler measurements of peak aortic acceleration and velocity in the evaluation of left ventricular function, e.g., to detect or exclude the presence of coronary artery disease.

Adolescent↗

Phycocyanin: laser activation, cytotoxic effects, and uptake in human atherosclerotic plaque.

Phycocyanin is a phycobiliprotein with peak absorption at 620 nm. The laser activation, cytotoxic effects, and uptake into atherosclerotic plaque of phycocyanin was studied. Optimal activation was produced by argon dye laser at 0.5 W and a total energy dose of 300 J/cm2 at 620 nm and 650 nm, irradiated through blood with a hematocrit of 8%. Activation was evidenced by reduction of optical density by 0.3 units at 340 nm caused by oxidation of the reduced nicotinamide adenine dinucleotide phosphate (NADPH) in a buffered reaction solution containing 0.1 mg/ml of phycocyanin. Cytotoxicity was evaluated by measuring viability of mouse myeloma cells in culture after incubation with phycocyanin (0.25 mg/ml) and irradiated by 300 J/cm2 at 514 nm. After 72 hours post-treatment the cells showed 15% viability compared to 69% and 71% for control cells exposed to laser only or phycocyanin only, respectively. Atherosclerotic artery segments obtained within 5 hours postmortem were perfused with 0.1 mg/ml phycocyanin in oxygenated Krebs Ringer solution at 30 mm Hg for 5 minutes followed by washout with phycocyanin-free Krebs for 10 minutes. Artery sections examined histologically by light and fluorescence microscopy showed specific fluorescence localization within the plaque particularly at the elastic laminae and to a larger extent at the internal elastic lamina but not in the medial muscle layer. In conclusion, phycocyanin is a cytotoxic photosensitizer that exhibits specific binding to plaque and is activated at a wavelength minimally absorbed by blood. These properties suggest potential therapeutic use for plaque localization and regression.

Coronary Artery Disease↗

Effect of laser-heated tip angioplasty on human atherosclerotic coronary arteries.

Effects of laser-heated-tip angioplasty on arteries is not fully understood. We report histology, ultrasound image properties, and vasoreactivity of human atherosclerotic coronary arteries after exposure to the laser-heated tip catheter. Segments of isolated human coronary arteries were obtained within 5-8 hours postmortem. Side branches were ligated and perfused with Krebs-Ringer solution. Coronary occlusions were recanalized during perfusion using a 1.5-mm tip heated twice with a 10 W argon laser for 10 seconds while two-dimensional 12-MHz ultrasound images were recorded. Images documented vessel recanalization and an increase in ultrasound refractile properties of vessel walls adjacent and 2-5 mm distal to the heated tip. Histologic studies showed charring along the neolumen and extensive coagulation pattern within the plaque. Vasoreactivity was assessed by measuring flow rate changes during perfusion with 100 ml of 10(-5) M serotonin followed by washout with serotonin-free solution. Recanalized arteries showed a 50% increase in magnitude of vasospasm, which was persistent for 5 hours, compared to control atherosclerotic vessels, which relaxed within 30 minutes. In conclusion, laser-heated-tip-irradiated vessels demonstrated plaque coagulation, increased ultrasound refractile properties of plaque, and increased vasospasm, which persisted for several hours.

Angioplasty, Balloon↗

Exercise testing in patients with life-threatening ventricular tachyarrhythmias: results and correlation with clinical and arrhythmia factors.

The results of exercise treadmill stress testing were analyzed in 64 consecutive patients presenting with either ventricular fibrillation (42%) or hemodynamically significant ventricular tachycardia (58%). Underlying diseases included coronary artery disease (55%), dilated cardiomyopathy (16%), and miscellaneous disorders (29%). Patients were additionally studied with ambulatory electrocardiographic monitoring and programmed stimulation. During exercise testing, 22 patients (34%) had nonsustained and five (8%) had sustained ventricular tachycardia. No patient experienced ventricular fibrillation or a major complication during exercise testing. Patients with a history of ventricular fibrillation were significantly less likely to have exercise-induced ventricular tachycardia than those with a history of ventricular tachycardia. Other clinical factors were not associated with the results of exercise testing. The results of programmed stimulation did not correlate with the results of exercise testing. Ventricular tachycardia was commonly documented during ambulatory monitoring (72%), but this was not predictive of ventricular tachycardia during exercise. However, patients who did not have ventricular tachycardia during ambulatory monitoring were predictably unlikely to have it during exercise testing (p less than 0.002). Thus exercise testing is safe and can provoke ventricular tachycardia in a significant proportion of patients with life-threatening arrhythmias.

Cardiac Pacing, Artificial↗

Beta-blocker therapy in patients with ventricular tachyarrhythmias in the setting of left ventricular dysfunction.

Although several studies suggest beta blockers (BB) are effective in suppressing ventricular arrhythmias, less is known about their role in the treatment of patients with ventricular tachyarrhythmias associated with impaired left ventricular function. To assess the tolerance and efficacy of these agents, 32 patients presenting with either ventricular fibrillation (18) or sustained ventricular tachycardia (14) were studied during BB therapy. Left ventricular dysfunction (mean ejection fraction 29%) was present as a consequence of coronary artery disease (26) or cardiomyopathy (6). Baseline arrhythmia assessment revealed recurrent ventricular tachycardia in all patients. Antiarrhythmic drug therapy including BB was guided by programmed stimulation (10), exercise testing (8), ambulatory monitoring (12), or was given empirically (2). Beta blockers were well tolerated, as measured by exercise duration, which improved significantly, and by long-term maintenance, which continued in 23 of 32 (72%) patients. Over a mean follow-up of 668 days, patients treated with BB had a relatively low incidence of both sudden (3%) and nonsudden (9%) death. Thus, BB can be effective and well tolerated adjunct therapy in patients with a history of ventricular tachyarrhythmias in the setting of impaired left ventricular function.

Adrenergic beta-Antagonists↗

Doppler flow velocity mapping in an in vitro model of the normal pulmonary artery.

Pulsed Doppler pulmonary artery velocity measurements are useful in evaluating a number of cardiac conditions including pulmonary hypertension, pulmonary stenosis and insufficiency, intracardiac shunts and other congenital abnormalities. However, variations in sample location relative to the arterial wall and valve have been thought to affect pulmonary artery velocity and acceleration measurements clinically. Therefore, pulsed Doppler and color flow mapping were performed in a pulsatile flow apparatus connected to a glass or Plexiglas model of the main pulmonary artery and its bifurcation, which contained a Hancock 29 mm pericardial tissue valve (5.35 cm2 orifice). Doppler sample volumes were placed at four sites: 1) at the pulmonary valve leaflet tips, centrally; 2) 2 cm distal to the leaflet tips, centrally; 3) 2 cm distal but laterally near the pulmonary artery wall; and 4) at the pulmonary artery bifurcation, centrally. Doppler peak flow velocity and acceleration time were measured. There was no difference between sites 1 and 2 in peak flow velocity or acceleration time. At site 3, peak flow velocity and acceleration time were both less than at site 1 (mean +/- SD, 85 +/- 44 versus 105 +/- 39 cm/s, p less than 0.005, and 162 +/- 65 versus 188 +/- 46 ms, p less than 0.03, respectively). Moreover, the pulmonary artery velocity contour at site 3 exhibited increased spectral dispersion and notching and increased variance on the color spectrum. At site 4, peak flow velocity was less than at site 1 (85 +/- 31 versus 105 +/- 39 cm/s, p less than 0.005), whereas pulmonary artery acceleration time was not significantly different. In this model, Doppler pulmonary artery flow velocity was best recorded within 2 cm of the valve and in the center of the vessel. Similar studies should be performed in the human pulmonary artery to standardize the recording technique and sample sites for Doppler measurements of velocity and acceleration.

Blood Flow Velocity↗

Arginine metabolism in wounds.

Arginine metabolism in wounds was investigated in the rat in 1) lambda-carrageenan-wounded skeletal muscle, 2) Schilling chambers, and 3) subcutaneous polyvinyl alcohol sponges. All showed decreased arginine and elevated ornithine contents and high arginase activity. Arginase could be brought to the wound by macrophages, which were found to contain arginase activity. However, arginase was expressed by macrophages only after cell lysis and no arginase was released by viable macrophages in vitro. Thus the extracellular arginase of wounds may derive from dead macrophages within the injured tissue. Wound and peritoneal macrophages exhibited arginase deiminase activity as demonstrated by the conversion of [guanido-14C]arginine to radiolabeled citrulline during culture, the inhibition of this reaction by formamidinium acetate, and the lack of prokaryotic contamination of the cultures. These findings and the known metabolic fates of the products of arginase and arginine deiminase in the cellular populations of the wound suggest the possibility of cooperativity among cells for the production of substrates for collagen synthesis.

Amino Acids↗