Change In Lumen Area Research Articles

<b>Poststenting Axial Redistribution of Atherosclerotic Plaque Into the Reference Segments and Lumen Reduction at the Stent Edge</b>

Lumen enlargement during coronary stenting results from vessel expansion and axial redistribution of atheromatous plaque along the stented segment and proximal and distal reference segments. Plaque burden predicts stenosis at the stent edge. The aim of this study was to investigate the fate of shifted plaque with special reference to whether or not plaque shift (PSh) correlates with late lumen reduction. This is a prospective study conducted on 54 consecutive patients who underwent bare metal stenting. In all stent edges (108 edges), PSh volume was measured as postintervention plaque-media volume (PMV) minus preintervention PMV. Changes in lumen volume (DeltaLV), vessel volume (DeltaVV), and PMV (DeltaPMV) were measured by serial intravascular ultrasound (IVUS) examination. After stenting, PSh was detected in 81.5% of proximal edges versus 72.2% of distal edges (P = 0.36). It correlated significantly with DeltaVV (r = 0.34, P = 0.002), and inversely with DeltaLV (r = 0.32, P = 0.003). However, at 6-month follow-up, it did not correlate with DeltaLV (r = -0.03, P = 0.8), DeltaVV (r = 0.1, P = 0.6), or DeltaPMV (r = 0.1, P = 0.4). Furthermore, DeltaLV correlated more strongly with DeltaVV (r = 0.62, P < 0.00001) than with DeltaPMV (r = -0.39, P = 0.001). By multivariate analysis, PSh area was an independent predictor of the postintervention change in lumen area (partial eta squared 0.21, P = 0.01), but not the follow-up change. Two patients (3.7%) developed proximal edge stenosis with no evident PSh after stenting. Thus, axial redistribution of atheromatous plaque into the reference segments was frequently encountered after stenting. Although PSh correlated with the immediate reduction in stent edge lumen volume, it did not correlate with the late lumen reduction.

Comparison between three‐dimensional volume‐selective turbo spin‐echo imaging and two‐dimensional ultrasound for assessing carotid artery structure and function

To compare a volume-selective three-dimensional turbo spin echo (TSE) technique with ultrasound (US) for assessing carotid artery wall structure and function. A three-dimensional volume-selective TSE technique was used to image the carotid artery in 10 healthy subjects and five hypertensive subjects (each of whom were scanned three times while they received different hypertension treatments). Lumen and wall area were measured on MR images. Two-dimensional US measurements of the intima-media thickness (IMT) and lumen diameter were taken in three orientations through a single cross section. The lumen area change over the cardiac cycle was used to determine distension. For validation, a Bland-Altman analysis was used to compare the vessel wall and lumen areas measured by three-dimensional MRI volumes with those obtained by US scans. Agreement between the two methods was found. The mean difference in distension between US and MRI was 1.2% (+/-5.1%). For the wall area measurements, good agreement was shown, but there was a systematic difference due to the visualization of the adventitia by MRI. Both techniques offer an easy way to objectively measure lumen indices. MRI can provide the complete circumference over the length of a vessel, while US is flexible and relatively inexpensive. The application of US is limited, however, when subjects are poorly echogenic. A difference between hypertensive and healthy subjects was found. There was a good agreement between MRI and the clinically established two-dimensional US method. The MRI method has the advantage of providing increased vessel coverage, which permits one to assess localized abnormalities without assuming vessel uniformity.

Impact of age and hyperglycemia on the mechanical behavior of intact human coronary arteries: an ex vivo intravascular ultrasound study.

Despite their advantages, percutaneous coronary interventional procedures are less effective in diabetic patients. Changes in the mechanical properties of vascular walls secondary to long-term hyperglycemia as well as other factors such as age may influence coronary distensibility. This investigation is aimed at deciphering the extent of these effects on distensibility of postmortem human coronary arteries in a controlled manner. Excised human left anterior descending (LAD) coronary arteries were obtained within 24 h postmortem. With the use of intravascular ultrasound, vascular deformation was analyzed at midregions of 51 moderate lesions. Intraluminal pressure was systematically altered using a computerized pressure pump system and monitored by a pressure-sensing guidewire. Distensibility, a normalized compliance term, was defined as the change in lumen area normalized by the initial reference area over a given pressure interval. With the use of multivariate analysis and repeated-measures ANOVA, coronary distensibility was independently influenced by hyperglycemia and age (P < 0.05) through the entire pressure range. Within physiological pressure range, distensibility was significantly reduced with age in nonhyperglycemic coronary specimens (10.55 +/- 4.41 vs. 6.99 +/- 2.45, x10(3) kPa(-1), P = 0.01), whereas the hyperglycemic vessels were stiff even in the younger group (7.90 +/- 5.82 vs. 7.20 +/- 3.36, x10(3) kPa(-1), P = 0.79). Similar results were observed with stiffness index and elastic modulus of the arteries. Hyperglycemia and age independently influenced the distensibility of moderately atherosclerotic LAD coronary arteries. The stiffening with age was overshadowed in the hyperglycemic group by as-yet-undetermined factors.

Zinc reduces intimal hyperplasia in the rat carotid injury model

Background: The response to arterial injury following balloon dilatation is known to involve proliferative and inflammatory processes. The current widespread use of stents to maintain arterial patency not only does not eliminate but possibly exaggerates the proliferative and inflammatory phenotype and although drug-eluting stents are available, their long-term safety is yet to be determined. Zinc is a trace element that serves as a cofactor of many enzymes. Interestingly, it has been shown to have anti-inflammatory and anti-proliferative properties. We thus sought to investigate its effect on smooth muscle cell proliferation and intimal thickening in the rat carotid artery injury model. Methods and results: Smooth muscle cells (SMC) were cultured from carotid arteries of rats and proliferation was assessed by thymidine incorporation after exposure to different concentrations of zinc. Next, carotid artery injury was induced in rats by balloon dilatation and they were either treated with I.P injections of zinc or PBS for 2 weeks until sacrifice for assessment of neointimal formation and lumen area. Zinc inhibited in vitro SMC proliferation in a dose-dependent manner. In vivo, zinc treatment resulted in a 50% reduction in neointimal area and a significant decrease in neointimal/media ratio with no significant change in lumen area. Conclusion: Thus, zinc appears to reduce neointimal growth and should be tested by local delivery systems including stent coatings.

Spectrum of remodeling behavior observed with serial Long-Term (≥12 months) Follow-Up intravascular ultrasound studies in left main coronary arteries

Most intravascular ultrasound (IVUS) studies of arterial remodeling in native coronary arteries reported a remodeling index obtained at a single time point. We analyzed serial IVUS examinations, including the vessel cross-sectional area changes (remodeling behavior), of 60 hemodynamically nonstenotic left main lesions (baseline vs 18.4 ± 9.4 months follow-up). Lumen reduction resulted from vessel reduction (sometimes despite plaque + media decrease), plaque + media increase (with or without vessel increase), or both. The percent annual changes in lumen area correlated strongly with changes in vessel (r = 0.84), but not with changes in plaque + media area. Plaques were classified as group A lesions, reflecting positive remodeling behavior (vessel changes >0), or group B lesions, reflecting negative (or intermediate) remodeling behavior (vessel changes ≤0). Both groups did not differ significantly in demographics, laboratory data, and medications. Group A lesions (n = 40) more often showed plaque + media increase than group B lesions (32 of 40 [80%] vs 9 of 20 [45%]; p = 0.02). Group A lesions had, on average, mild annual lumen increase despite mild plaque + media increase, i.e, overcompensation of remodeling for plaque + media increase (vessel increase greater than plaque + media area increase, 19 of 40 [47%]). Conversely, group B lesions (n = 20) showed a significant lumen area reduction (−2.8 ± 2.6 mm 2/year) as a result of a decrease in vessel area only. Thus, serial long-term reduction of lumen size may result from vessel shrinkage (sometimes despite plaque decrease), plaque increase (with or without vessel increase), or both; overall, only the remodeling behavior has a significant relation to lumen changes. More than 30% of lesions show a negative remodeling behavior, which shows no relation to patient characteristics or initial plaque burden.

Effects of β-radiation with a 188rhenium-filled balloon catheter system on non-stented adjacent coronary artery segments

Background: The effects of β-radiation with a 188rhenium ( 188Re)-filled balloon catheter system on angiographically normal reference segments have not been well defined. Methods: In the Seoul National University Post-Angioplasty Rhenium irradiation (SPARE) trial, patients with de novo or restenotic lesions were first treated with a conventional catheter-based technique and then randomized to either a radiation group or a control group. Irradiation was performed using a 188Re-filled conventional balloon catheter system. Among 97 radiation group enrolled in this study from April 1998 through May 2001, 20 patients with de novo lesions who received brachytherapy with a balloon at least 10 mm longer than the length of an implanted stent, were selected and their post-intervention and follow-up intravascular ultrasound (IVUS) images were analyzed. Each reference segment was divided into two segments; full dose-irradiation with injury segment (irradiated segment; from the stent edge to the radiopaque balloon markers), and low dose-irradiation without injury segment (edge segment; 5-mm long segment proximal or distal to the location of radiopaque markers). In control group, serial IVUS analysis was available only in 10 patients, and IVUS parameters of the non-stented adjacent segments in these patients were compared to those of irradiated segments in radiation group patients. Results: Forty irradiated and 38 edge segments of the 20 radiation group patients were analyzed. In proximal irradiated segments, no significant changes were found in external elastic membrane (EEM), lumen or in the plaque plus media (P&M) areas. In distal irradiated segments, significant increases in the EEM (12.5±4.5 to 14.0±5.0 mm 2, P<0.01) and P&M areas (5.5±2.0 to 6.6±2.3 mm 2, P<0.01) were found to occur without a change in lumen area. In proximal edge segments, P&M areas were significantly increased (9.0±1.7 to 10.5±2.6 mm 2, P=0.03). No significant changes in EEM, lumen or P&M areas were observed in the distal edge segments. Comparisons between the irradiated segments ( n=40) in the radiation group and the non-stented adjacent segments ( n=19) in the control group showed a significant difference in the percentage change of EEM areas (18.5±33.2% in radiation group vs. −3.1±32.1% in control group, P=0.02). Conclusions: β-radiation with a 188Re-filled conventional balloon catheter system appears to have no significant deleterious effect on angiographically normal reference segments over a 6 months follow up after brachytherapy.

Impact of deep vessel wall injury and vessel stretching on subsequent arterial remodeling after balloon angioplasty: A serial intravascular ultrasound study

Background Arterial remodeling has been shown to be responsible for lumen narrowing after nonstent interventions. Methods To examine the impact of deep vessel wall injury (DI) after balloon angioplasty on the subsequent vessel remodeling process, we performed serial intravascular ultrasound (IVUS) analysis in 47 native coronary artery lesions that underwent balloon angioplasty. An IVUS study was performed before and after balloon angioplasty and repeated at follow-up. Vessel and lumen area were measured at the narrowest site before intervention. Plaque area was calculated as vessel area minus lumen area. DI was defined as the presence of plaque/vessel wall fracture deep in the medial layer (sonolucent zone by IVUS) after angioplasty. Results After angioplasty, DI was present in 18 (38%, DI group) and absent in 29 (62%, non-DI group) of lesions. During follow-up, changes in vessel area in the DI group were significantly larger than in the non-DI group (P =.007). There were no significant differences in changes in plaque area. A trend toward greater late lumen loss was observed in the non-DI group (P =.05). In the DI group, changes in lumen area correlated better with changes in vessel area (r = 0.81, P <.0001) than with changes in plaque area (r = 0.32, P =.20). However, in the non-DI group, changes in lumen area correlated with changes in plaque area (r = −0.55, P =.002), but not with changes in vessel area (r = 0.30, P =.11). Conclusions Deep vessel wall injury after balloon angioplasty is associated with the magnitude of the subsequent vessel remodeling process. The differences in the remodeling process may have implications regarding adjunctive therapies to prevent restenosis after balloon angioplasty. (Am Heart J 2002;144:323-8.)

Gamma radiation induces positive vascular remodeling after balloon angioplasty: A prospective, randomized intravascular ultrasound scan study

Background: Endovascular brachytherapy (EBT) has been shown to prevent restenosis after percutaneous transluminal coronary angioplasty (PTA) in both animal and clinical studies. However, as yet, the effect of EBT on peripheral arteries is unknown. Objective: This intravascular ultrasound scan (IVUS) study evaluates the effect of EBT on the extent of plaque growth and vascular remodeling after PTA of the femoropopliteal artery. Methods: Twenty-four patients with obstructive disease of the femoropopliteal artery underwent standard PTA. Patients were randomized to receive no additional therapy or additional EBT (192-Iridium) after PTA. IVUS investigation was performed after PTA and at 6-month follow-up. A comparison was made between patients without EBT (n = 16) and with EBT (n = 8) in the change in lumen, vessel, and plaque area and plaque dissections seen with IVUS at 6-month follow-up. Results: At follow-up, IVUS revealed a significant difference in lumen area change between patients without and with EBT (−9% and +23%, respectively; P = .03). This difference was the result of a significant difference in vessel area change (+2% and +19%, respectively; P = .05). In both groups of patients, a similar increase in plaque area (+12% and +16%, respectively; P = .80) was encountered. Plaque dissections encountered immediately after PTA were absent at follow-up in patients without EBT, whereas in four of the eight patients with EBT, a persistent dissection was encountered. Conclusion: This randomized IVUS study showed that γ-radiation after PTA has a positive effect on lumen dimensions at 6-month follow-up by inducing positive vascular remodeling (ie, vascular dilatation); γ-radiation seemed not to affect plaque growth. In addition, γ-radiation has an effect on the healing process of dissections after PTA. (J Vasc Surg 2002;36:318-24.)

Coronary artery restenosis after atherectomy is primarily due to negative remodeling

The primary cause of restenosis following directional coronary atherectomy (DCA) remains obscure. “Negative remodeling,” a decrease in vessel area, is believed to be more causative than is increase in plaque area. The DCA technique used in these patients, designed to facilitate the removal of plaque, should allow a more precise evaluation of the relative roles of these two mechanisms. Twenty-five patients underwent DCA. In 17, complete angiographic and intravascular ultrasound (IVUS) images were obtained before and after DCA and at follow-up (6 to 9 months). Internal elastic lamina (IEL), lumen, and plaque areas were calculated at preatherectomy, postatherectomy, and follow-up. Postatherectomy, the mean IEL area increased by 32% and the mean plaque area decreased by 51%, resulting in a significant mean increase in lumen area, 500%. At follow-up when compared to postatherectomy, the change in IEL area was variable; however, the mean did not change significantly (p = 0.58). Plaque area change, when standardized for initial vessel size, was small (mean increase 2.8 ± 3.5%). The mean lumen area did not decrease significantly at follow-up (p = 0.43). A highly significant correlation (r = 0.96) was noted between IEL area change and lumen area at follow-up. In contrast, the correlation between plaque area change and lumen area change over the same period was much less significant (r = 0.64). These data indicate that decrease in IEL area primarily is responsible for restenosis.

Plaque area increase and vascular remodeling contribute to lumen area change after percutaneous transluminal angioplasty of the femoropopliteal artery: An intravascular ultrasound study

Objective: The aim of the study was to assess the change in lumen area (LA), plaque area (PLA), and vessel area (VA) after percutaneous transluminal angioplasty (PTA) of the femoropopliteal artery. Methods: This was a prospective study. Twenty patients were studied with intravascular ultrasound (IVUS) immediately after PTA and at follow-up examination. Multiple corresponding IVUS cross-sections were analyzed at the segments that were dilated by PTA (ie, treated sites; n = 168), including the most stenotic site (n = 20) and the nondilated segments (ie, reference sites; n = 77). Results: At follow-up examination, both the PLA increase (13%) and the VA decrease (9%) resulted in a significant LA decrease (43%) at the most stenotic sites ( P = .001). At the treated sites, the LA decrease (15%) was smaller and was caused by the PLA increase (15%). At the reference sites, the PLA increase (15%) and the VA increase (6%) resulted in a slight LA decrease (3%). An analysis of the IVUS cross-sections that were grouped according to LA change (difference ≥10%) revealed a similar PLA increase in all the groups: the type of vascular remodeling (VA decrease, no change, or increase) determined the LA change. At the treated sites, the LA change and the VA change correlated closely ( r = 0.77, P < .001). At the treated sites, significantly more PLA increase was seen in the IVUS cross-sections that showed hard lesion or media rupture ( P < .05). No relationhip was found between the presence of dissection and the quantitative changes. Conclusion: At the most stenotic sites, lumen narrowing was caused by plaque increase and vessel shrinkage. Both the treated sites and the reference sites showed a significant PLA increase: the type of vascular remodeling determined the LA change at follow-up examination. The extent of the PLA increase was significantly larger in the IVUS cross-sections that showed hard lesion or media rupture. (J Vasc Surg 1999;29:430-41.)

Intravascular ultrasound observations of atherosclerotic lesion formation and restenosis in patients with diabetes mellitus.

Coronary artery disease is more aggressive in diabetic patients than in nondiabetics; they have more diffuse disease, higher mortality rates and worse clinical outcomes after coronary interventions. Intravascular ultrasound (IVUS) produces transmural tomographic images of the coronary arteries in vivo. Recent IVUS studies have provided new insights into the mechanisms of stenosis formation and restenosis in both nondiabetic and diabetic patients. Arterial remodeling is defined as a change in arterial area. During atherogenesis, an increase in arterial area usually accompanies plaque accumulation to delay lumen compromise. Stenosis formation is related to: (a) the rate of plaque accumulation versus the rate of positive remodeling; and (b) the limits and ultimate failure of positive remodeling. However, there is a marked variability in remodeling. IVUS studies have suggested that remodeling may be impaired in some diabetic patients during atherogenesis. Following non-stent catheter-based interventions, serial (post-intervention and follow-up) IVUS studies have shown that the change in lumen area correlates better with the change in arterial area (remodeling) than with the change in plaque area (neointimal hyperplasia). In some patients, a positive remodeling response mitigates against the increase in plaque area to limit late lumen loss and restenosis. Neointimal hyperplasia is exaggerated in diabetic patients. Despite this, there is a reduced frequency of positive remodeling, potentially similar to the impaired positive remodeling in some diabetic patients during atherogenesis. Failed or inadequate arterial remodeling may contribute to the pathogenesis and natural history of atherosclerotic coronary artery disease in diabetic patients.

Remodeling of human coronary arteries undergoing coronary angioplasty or atherectomy.

Recently, long-term constriction of the vessel has been suggested as an alternative mechanism of restenosis after coronary angioplasty. To understand remodeling of human coronary arteries undergoing coronary angioplasty or atherectomy, serial intravascular ultrasonographic examinations were performed at preintervention and postintervention examinations and at 24 hours, 1 month, and 6 months. Complete serial data were obtained in 61 lesions (balloon angioplasty, 35 lesions; directional atherectomy, 26 lesions). Lumen area improved from 6.81+/-2.24 mm2 after intervention to 8.22+/-2.79 mm2 at 1 month (P=.0001) and decreased to 4.88+/-2.86 mm2 at 6 months (P=.0001). Vessel area enlarged from 17.32+/-5.35 mm2 after intervention to 19.39+/-5.33 mm2 at 1 month (P=.0001) and decreased to 16.33+/-5.54 mm2 at 6 months (P=.0001). Plaque+media area increased significantly from postintervention examination to 24 hours (10.51+/-4.38 versus 10.96+/-4.49 mm2, P=.0008) and from 24 hours to 6 months (10.96+/-4.49 versus 11.45+/-4.45 mm2, P=.03). Changes in lumen area in each study interval correlated more closely with changes in vessel area than with changes in plaque+media area. Restenotic lesions compared with nonrestenotic lesions had a greater decrease in the vessel area between 1 month and 6 months (-4.33+/-2.73 versus -2.49+/-2.15 mm2, P=.006) and greater increase in the plaque+media area both within 24 hours (0.84+/-1.22 versus 0.27+/-0.38 mm2, P=.04) and between 24 hours and 6 months (1.19+/-2.19 versus 0.18+/-1.46 mm2, P=.04). CONCLUSIONS; Remodeling after coronary angioplasty or atherectomy was characterized by early adaptive enlargement and late constriction of the vessel.

Mechanisms of luminal enlargement and quantification of vessel wall trauma following balloon coronary angioplasty and directional atherectomy.

The purpose of this study was to assess the dual action of lumen enlargement and vessel wall damage following either balloon angioplasty or directional atherectomy, using intracoronary ultrasound, and angioscopy. Differences in the mechanisms of action of balloon angioplasty and directional atherectomy may have a significant bearing on the immediate outcome and the restenosis rate at 6 months. A total of 36 patients were studied before and after either balloon angioplasty (n = 18) or directional atherectomy (n = 18). Ultrasound measurements included changes in lumen area, external elastic membrane area and plaque burden. In addition, the presence and extent of dissections were assessed to derive a damage score. Angioscopic assessment of the dilated or atherectomized stenotic lesions was translated into semi-quantitative dissection, thrombus and haemorrhage scores. Atherectomy patients had a larger angiographic vessel size compared with the angioplasty group (3.55 +/- 0.46 mm vs 3.00 +/- 0.64 mm, P < 0.05); however, minimal lumen diameter (1.18 +/- 0.96 mm vs 0.85 +/- 0.49 mm) and plaque burden (17.04 +/- 3.69 vs 15.23 +/- 4.92 mm2) measurements did not differ significantly. As a result of plaque reduction, atherectomy produced a larger increase in luminal area than the angioplasty group (5.80 +/- 1.78 mm2 vs 2.44 +/- 1.36 mm2, P < 0.0001). Lumen increase after angioplasty was the result of 'plaque compression' (50%) and wall stretching (50%). Additionally, in both groups there was indirect angioscopic evidence of thrombus 'microembolization' as an adjunctive mechanism of lumen enlargement. Angioscopy identified big flaps in six and small intimal flaps in 11 of the atherectomized patients as compared with five and 12 patients in the angioplasty group. Changes in thrombus score following both coronary interventions were identical (0.72 +/- 3.42 points atherectomy vs -0.38 +/- 3.27 points balloon angioplasty, ns). Lumen enlargement after directional atherectomy is mainly achieved by plaque removal (87%), whereas balloon dilation is the result of vessel wall stretching (50%) and plaque reduction (50%). Despite the fact that the luminal gain achieved by directional atherectomy is twice that achieved with balloon angioplasty, the extent of trauma induced by both techniques seems to be similar.

Contribution of age and intimal lesion morphology to coronary artery wall mechanics in coronary artery disease.

1. Atherosclerotic changes of the coronary vascular wall include localized plaque formation and diffuse hardening, both of which influence tensile strength of the inner vascular wall. Insight into the relation between age, the atherosclerotic process and vessel wall elasticity may contribute to the prevention of secondary vascular wall damage. 2. To evaluate the determinants of coronary artery wall elasticity, we studied a group of 34 patients, aged 54.6 +/- 10.1 years, who underwent balloon angioplasty for coronary artery disease. With the use of 30 MHz intravascular ultrasound, a total of 127 cross-sections of coronary artery segments outside the balloon area were studied. The echographic appearance of the intima was classified as normal intimal thickening, fibrous lesions and calcified lesions. Fibrofatty lesions, which are believed to be rupture prone, were analysed separately. From the lumen area change, measured by semiautomated planimetry from digitized ultrasound images, and simultaneously measured aortic pressure change during the diastolic phase of the cardiac cycle, two elastic parameters were derived, pressure-strain modulus Ep and beta-stiffness. 3. In univariate analysis Ep and beta-stiffness were determined by age, vessel size, intimal composition, severity of lumen obstruction and gender, but not by eccentricity of the lesion or a specific coronary artery. In multivariate linear analysis, increased vessel wall stiffness was independently determined by advanced age, larger vessel size, intimal composition, and to a lesser extent by female gender. Elastic parameters of fibrofatty lesions were not different from other fibrous lesions. 4. Coronary artery wall elasticity is independently determined by age, vessel size and intimal composition.

Contribution of endothelium-derived nitric oxide to coronary arterial distensibility: An in vivo two-dimensional intravascular ultrasound study

Reduced epicardial coronary arterial disteinsibility associated with early atherosclerosis may be mediated in part by reduced nitric oxide (NO) release. To directly assess the contribution of endogenous NO to coronary arterial distensibility, we examined the effect of intracoronary N ω nitro- l-arginine methyl ester ( l-NAME), an inhibitor of NO synthase, and l-arginine, its natural substrate, on the circumflex artery in seven anesthetized dogs. We also used intracoronary acetylcholine to examine the effect of pharmacologically induced NO release on coronary distensibility. Electrocardiographically gated measurements of epicardial coronary lumen area were made by a blinded observer from images obtained with a 4.3F, 30 MHz intravascular ultrasound catheter. Aortic root pressure was continuously monitored, and neither systemic arterial pressure nor pulse pressure changed significantly with intracoronary drug administration. Change in lumen area (ΔLA) from end systole to end disatole was measured, and an arterial distensibility index was calculated. ΔLA increased with acetylcholine from 8.2% ± 0.5% at baseline to 16.3% ± 2.8% (10 −6 mol/L; p < 0.001), with increases in both end-systolic and end-diastolic lumen area. l-NAME (10 −4 mol/L) decreased both end-systolic and end-diastolic lumen area and decreased ΔLA to 3.1% ± 1.3% ( p < 0.01) Lumen area and ΔLA were both restored to baseline by l-arginine (10 −4). The calculation distensibility index of the epicardial coronary artery was enhanced by acetylcholine, reduced below baseline by l-NAME, and restored to baseline by l-arginine. Balloon denudation of the left anterior descending coronary artery caused small increases in end-systolic and end-diastolic lumen areas, but decreased ΔLA in the denuded segment (to 4.4% ± 1.4%, p < 0.01) and the coronary artery distensibility index. Thus epicardial coronary artery distensibility is modulated by both basal and induced release of endothelium-derived NO. The endothelial dysfunction associated with early atherosclerosis may thus decrease coronary arterial distensibility even before structural changes in the blood vessels.

Temporal relationship between androgen-dependent changes in the volume of seminiferous tubule fluid, lumen size and seminiferous tubule protein secretion in rats

This study assessed whether changes in production of seminiferous tubule fluid underlie the previously described androgen-dependent changes in protein secretion by seminiferous tubules at stages VI-VIII of the spermatogenic cycle. Testosterone withdrawal was induced in adult rats by administration of ethane dimethane sulfonate (EDS) and temporal changes in lumen area, the volume of seminiferous tubule fluid and testicular interstitial fluid were assessed and compared with the changes in secretion of [35S]methionine-labelled proteins in vitro by isolated seminiferous tubules at stages VI-VIII. Testicular interstitial fluid was reduced by about 50% by day 4 and later after EDS treatment when compared with controls. In contrast, the volume of seminiferous tubule fluid was unaffected at days 3 and 4 but was reduced by about 50% at days 6 and 8 after EDS treatment. In perfusion-fixed control testes, the lumen area of seminiferous tubules at stages VII-VIII was significantly greater than at stages I-VI and IX-XIV. This difference was also evident at 4 days after EDS treatment, but was abolished at 6 and 8 days after treatment. The volume of testicular interstitial fluid was reduced significantly at 3 and 4 days after EDS treatment, but was further reduced (about 50%) at 6 and 8 days. Administration of 25 mg testosterone esters every 3 days to EDS-treated rats prevented all of the changes described above.(ABSTRACT TRUNCATED AT 250 WORDS)

Balloon angioplasty results in increased segmental coronary distensibiliy: A likely mechanism of percutaneous transluminal coronary angioplasty

Objectives. The purpose of this study was to evaluate the hypothesis that the increase in lumen area induced by percutaneous transluminal coronary angioplasty is secondary to a change in lesion (segmental) distensibility.Background. Despite the widespread use of coronary angioplasty, the precise mechanism (or mechanisms) of lumen area improvement remains poorly understood.Methods. Quantitative coronary angiography was used to measure the minimal (contrast agent filled) balloon diameters at 1 to 5 atm, inclusive, during the first and final balloon inflations in 24 lesions successfully treated with coronary angioplasty. To rule out possible confounding effects due to changes in balloon material distensibility during repeated inflations, five control balloons were studied ex vivo. In parallel, intravascular ultrasound imaging was utilized to compare the segmental distensibility (change in lumen area during the cardiac cycle) of eight disease-free and seven mildly diseased coronary segments and seven segments after successful balloon angioplasty.Results. Minimal balloon diameters increased significantly between the first and final inflations (46%, 33%, 26%, 14% and 10% at 1, 2, 3, 4 and 5 atm, respectively, all p < 0.0001), demonstrating an increase in arterial distensibility after successful coronary angioplasty. No significant changes in balloon diameters were observed during sequential initial inflations at 1 and 2 atm (n = 5). Minimal increases in Balloon diameters were observed during repeated balloon inflations in the ex vivo studies (4.9 ± 1% [mean ± SEM]). A distensibility index, derived from the intravascular ultrasound data, was not different between the balloon-dilated and the normal segments but was significantly lower in mildly diseased sites (14.7 ± 2.2 vs. 12.9 ± 1.2 vs. 6.9 ± 1.9, respectively, p < 0.05) despite a smaller plaque area (7.3 ± 1 vs. 11.3 ± 1 mm2, proximal/nondilated vs. dilated segments, respectively, p < 0.05).Conclusions. Coronary distensibility is significantly impaired in atherosclerotically diseased coronary segments and increases significantly after balloon angioplasty. This increase in segmental coronary compliance after coronary angioplasty may create a larger lumen area by allowing the vessel to distend in response to normal intraarterial pressure.

Measurement by intracoronary ultrasound of in vivo arterial distensibility within atherosclerotic lesions

Arterial distensibility is diminished by atherosclerosis. This process has not been well studied in the coronary arteries. The purpose of this study was to assess changes in coronary arterial distensibiltty in 4 groups of patients. Group I (n = 20) consisted of patients with normal vessels, group II (n = 40) with diseased undilated vessels, group III (n = 15) after successful percutaneous transluminal coronary angioplasty (PTCA), and Group IV (n = 20) after successful directional coronary atherectomy CDCA). Intracoronary ultrasound imaging was used to assess distensibiltty, plaque morphology and atherosclerotic burden (expressed as the percentage of total vessel cross-sectional area occupied by plaque: percent plaque area). Distensibility was defined as percent change in lumen area in a cardiac cycle. Group I (normal vessels) had a distensibility = 14 ± 5%, which was significantly greater than that seen in group II (distensibiltty = 4 ± 2%, p < 0.001). In undilated vessels, distensibiltty was related to the degree of atherosclerotic burden (r = 0.75). This relation was curvilinear with a marked decrease in distensibility when percent plaque area exceeded 30%. Distensibility in group III (after PTCA) was higher than in group II (10 ± 3 vs 4 ± 2%, p < 0.001) despite a larger plaque burden (percent plaque area of 56 ± 12 vs 46 ± 11%, p < 0.005). The distensibility in group IV (after DCA) was also higher than in group II (8 ± 4 vs 4 ± 2%, p < 0.001) despite a similar residual percent plaque area (49 ± 13 vs 46 ± 11%, p = NS). After PTCA, hard lesions had greater distensibility than soft lesions (distensibility = 11 ± 3 vs 8 ± 2%, p = 0.04), whereas after DCA hard lesions had less distensibility than soft lesions (distensibility = 6 ± 4 vs 10 ± 4%, p = 0.04). In conclusion, arterial distensibility is decreased by atherosclerosis wtth a marked reduction in even minimally diseased vessels. PTCA and DCA result in an increase in arterial distensibility at the site of the treated lesion. Hard lesions have greater distensibility after PTCA, suggesting greater plaque disruption in these lesions than in soft lesions. Hard lesions have less distensibiltty after DCA, consistent wtth less effective plaque cutting and removal in these lesions than in soft lesions. It is concluded that the study of arterial distensibiltty by intracoronary ultrasound provides insights into the mechanisms of interventional therapy and may be useful for the assessment of early atherosclerosis.

Mechanisms of angiographically successful directional coronary atherectomy: Evaluation by intracoronary ultrasound and comparison with transluminal coronary angioplasty

To assess the mechanisms of luminal improvement, 40 patients undergoing directional coronary atherectomy and a matched control group of 25 patients undergoing angioplasty were evaluated with intracoronary ultrasound imaging before and after intervention. Despite similar sized vessels, a similar angiographic severity of diameter stenosis (75 ± 12% for the angioplasty group vs 69 ± 15% for the atherectomy group, p = NS), and a similar plaque burden (percent plaque area) before intervention (84 ± 5% in the angioplasty group vs 85 ± 13% in the atherectomy group, p = NS), the residual plaque area after intervention was significantly smaller in the atherectomy group (54 ± 14%) compared with the angioplasty group (65 ± 13%, p = 0.002). Despite excellent angiographic results, significant residual plaque was noted after either successful intervention. Based on the absolute changes in lumen area, plaque area, and vessel area, improvement in the lumen area in the atherectomy group occurred as a result of plaque “compression” (48%), plaque removal (37%), and vessel expansion (15%). In the angioplasty group, plaque “compression” accounted for 94% of the improvement in lumen area, whereas vessel expansion contributed 6%. Thus “compression” of plaque remains the major mechanism of luminal improvement during atherectomy.

Application of intravascular ultrasound for detection and quantitation of coronary atherosclerosis

Although angiography is widely utilized to assess the extent and severity of coronary artery disease (CAD), arteriography yields only a silhouette of the vessel lumen. Coronary intravascular ultrasound supplements angiography by providing a tomographic perspective of lumen geometry and vessel wall structure. Intracoronary ultrasound can now be performed in vivo utilizing small, flexible probes capable of negotiating tortuous vessels. We have performed coronary ultrasound in more than 100 patients, including a group of normal subjects, with no serious complications. Measurements of coronary lumen dimensions by angiography and ultrasound correlated closely for normal vessels (r = 0.92) and for concentrically narrowed atherosclerotic vessels (r = 0.90). However, the correlation between angiography and ultrasound was only fair for eccentrically narrowed arteries (r = 0.79) and was poor following angioplasty (r = 0.30). Coronary artery wall motion was measured by intravascular ultrasound and demonstrated significant differences between normal arteries (18% lumen area change) and atherosclerotic vessels (11% change). Coronary ultrasound demonstrated important differences in the structure of normal and atherosclerotic vessel walls. Arteries in normal subjects exhibited a thin intimal leading-edge echo (mean 0.20 mm) and subadjacent sonolucent zone (mean 0.12 mm). Atherosclerotic vessels typically demonstrated increased thickness of both structures and often exhibited dense fibrocalcific plaques that shadowed underlying anatomy. These ultrasound abnormalities were often present at angiographically normal sites. Several limitations of coronary intravascular ultrasound were apparent, including echo 'dropout', distortions produced by non-coaxial imaging, and inability to image small or severely narrowed vessels. Coronary intravascular ultrasound holds great promise for the detection and quantification of CAD in the clinical setting.