Changes In Luminal Area Research Articles

Large conducting airway luminal area is not different after initiating cystic fibrosis transmembrane conductance regulatory modulator therapy

Background: Cystic fibrosis (CF) is a genetic disorder in which patients have dysfunctional cystic fibrosis transmembrane regulatory (CFTR) proteins in the lungs that disrupt ion regulation resulting in a thick, viscous mucus layer on the airway epithelium. Consequential poor mucociliary clearance leads to repeated infections and chronic inflammation contributing to bronchiectasis which is associated with increased airway luminal area. CFTR modulator therapy can improve and even restore the function and expression of a mutated CFTR gene which has been shown to improve sweat chloride levels and pulmonary symptoms rapidly. However, the effect of CFTR modulator therapy on large conducting airway luminal area is unclear. We compared large conducting airway luminal area in patients with CF before and after initiating CFTR modulator therapy. We hypothesized that airway luminal area would normalize (decrease) after initiating CFTR modulator therapy. Methods: Twenty-three patients with CF (32±15 years, 11 female) with computed tomography (CT) imaging of their lungs before and after initiating CFTR modulator therapy were included in analyses. In each patient we measured seven large conducting airways (trachea, left and right main bronchus, bronchus intermediate, left and right upper lobe, and left lower lobe) before and after CFTR modulator therapy initiation. To control the potential effect of height, airway luminal area (mm2) was divided by patient height (cm). Paired t-tests compared differences between luminal area before after initiating CFTR modulator therapy. Results: Patients were taking CFTR modulator therapy for a median of 1.1 years (range: 22–2111 days) at the time of their CT imaging after initiating CFTR modulator therapy. Large conducting airway luminal area was not different before and after initiating CFTR modulator therapy in all seven airways: trachea (1.50±0.35 vs. 1.56±0.34 mm2/cm, p=0.14), right main bronchus (1.05±0.21 vs. 1.09±0.19 mm2/cm, p=0.11), bronchus intermediate (0.68±0.16 vs. 0.68±0.16 mm2/cm, p=0.54), right upper lobe (0.42±0.10 vs. 0.45±0.09 mm2/cm, p=0.27), left main bronchus (0.81±0.19 vs. 0.83±0.18 mm2/cm, p=0.21), left upper lobe (0.51±0.13 vs. 0.52±0.13 mm2/cm, p=0.45), and left lower lobe (0.44±0.11 vs. 0.46±0.10 mm2/cm, p=0.42). Conclusion: There was no change in large conducting airway luminal area after initiating CFTR modulator therapy suggesting CFTR modulator therapy may not reverse CF-associated airway luminal area changes. However, longitudinal analysis and investigation into the small airways are necessary for a comprehensive understanding of the effect of CFTR modulator therapy on airway luminal area changes. Funding: NIH (HL139854 to MJJ, HL131151 to SEB) and NSERC (PDF-577750-2023 to AHR). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Radiation-induced airway changes and downstream ventilation decline in a swine model

Purpose. To investigate indirect radiation-induced changes in airways as precursors to atelectasis post radiation therapy (RT). Methods. Three Wisconsin Miniature Swine (WMS TM ) underwent a research course of 60 Gy in 5 fractions delivered to a targeted airway/vessel in the inferior left lung. The right lung received a max point dose <5 Gy. Airway segmentation was performed on the pre- and three months post-RT maximum inhale phase of the four-dimensional (4D) computed tomography (CT) scans. Changes in luminal area (Ai) and square root of wall area () for each airway were investigated. Changes in ventilation were assessed using the Jacobian ratio and were measured in three different regions: the inferior left lung <5 Gy (ILL), the superior left lung <5 Gy (SLL), and the contralateral right lung <5 Gy (RL). Results. Airways (n = 25) in the right lung for all swine showed no significant changes (p = 0.48) in Ai post-RT compared to pre-RT. Airways (n = 28) in the left lung of all swine were found to have a significant decrease (p < 0.001) in Ai post-RT compared to pre-RT, correlated (Pearson R = −0.97) with airway dose. Additionally, decreased significantly (p < 0.001) with airway dose. Lastly, the Jacobian ratio of the ILL (0.883) was lower than that of the SLL (0.932) and the RL (0.955). Conclusions. This work shows that for the swine analyzed, there were significant correlations between Ai and change with radiation dose. Additionally, there was a decrease in lung function in the regions of the lung supplied by the irradiated airways compared to the regions supplied by unirradiated airways. These results support the hypothesis that airway dose should be considered during treatment planning in order to potentially preserve functional lung and reduce lung toxicities.

Nonlinear pressure–velocity waveforms in large arteries, shock waves and wave separation

Nonlinear inviscid 1D blood flow equations were studied analytically using the method of characteristics. The initial–boundary value problem for a class of the initial–boundary conditions (including a triangle-shaped profile) at the aortic outlet was considered. The nonlinear pressure–velocity profile and shock conditions were derived as closed analytical expressions with second order accuracy on the relative luminal area change. Finally, the fully nonlinear wave separation expressions were obtained using the Riemann invariants. The results show good correspondence with the data from the literature.

STEREOLOGICAL STUDIES ON FETAL VASCULAR DEVELOPMENT IN HUMAN PLACENTAL VILLI

In human pregnancy, fetal well-being depends on the development of placental villi and the creation and maintenance of fetal microvessels within them. The aim of this study was to define stereological measures of the growth, capillarization and maturation of villi and of fetoplacental angiogenesis and capillary remodelling. Placentas were collected at 12-41 weeks of gestation and assigned to six age groups spanning equal age ranges. Tissue samples were randomised for position and orientation. Overall growth of peripheral (intermediate and terminal) villi and their capillaries was evaluated using total volumes, surface areas and lengths. Measures of villous capillarization comprised capillary volume, surface and length densities and capillary:villus surface and length ratios. Size and shape remodelling of villi and capillaries was assessed using mean cross-sectional areas, perimeters and shape coefficients (perimeter2/area). Group comparisons were drawn by analysis of variance. Villous and capillary volumes, surfaces and lengths increased significantly throughout gestation. Villous maturation involved phasic (capillary:villus surface and length ratios) or progressive (volume, surface and length densities) increases in indices of villous capillarization. It also involved isomorphic thinning (cross-sectional areas and perimeters declined but shape coefficients did not alter). In contrast, growth of capillaries did not involve changes in luminal areas or perimeters. The results show that villous growth and fetal angiogenesis involve increases in overall length rather than calibre and that villous differentiation involves increased capillarization. Although they do not distinguish between increases in the lengths versus numbers of capillary segments, other studies have shown that capillaries switch from branching to non-branching angiogenesis during gestation. Combined with maintenance of capillary calibres, these processes will contribute to the reduced fetal vascular impedances observed during pregnancy.

Comparison of Zotarolimus-Eluting Stents With Sirolimus-Eluting and Paclitaxel-Eluting Stents

Background— As a substudy of the large, randomized ZEST (Comparison of the Efficacy and Safety of Zotarolimus-Eluting Stent with Sirolimus-Eluting and PacliTaxel-Eluting Stent for Coronary Lesions) trial comparing first- and second-generation drug-eluting stents, we evaluated intimal hyperplasia (IH) and vascular changes using volumetric intravascular ultrasound analysis. Methods and Results— Complete angiographic and volumetric intravascular ultrasound data immediately after stenting and at 9-month follow-up were available in 162 patients with 183 lesions: 61 sirolimus-eluting stents (SES), 64 paclitaxel-eluting stents (PES), and 58 zotarolimus-eluting stents (ZES). External elastic membrane, stent, lumen, and peristent plaque volumes (external elastic membrane minus stent) were normalized by stent length. Percent IH volumes were calculated as [IH volume/stent volume]×100, %. Reduction of minimal luminal area) was greater in PES than SES (−1.4±1.5 mm 2 versus −0.7±0.9 mm 2 , P =0.003), whereas minimal luminal area change in ZES was not significantly different from SES (−1.2±1.0 mm 2 versus −0.7±0.9 mm 2 , P =0.055). Percent IH volume was less in SES compared with PES (9.8±6.0% versus 17.5±11.2%, P =0.002) or with ZES (9.8±6.0% versus 18.2±7.6%, P =0.005). Comparing ZES versus PES, there were no significant differences in %IH volume (17.5±11.2% versus 18.2±7.6%, P =0.779) or changes in normalized lumen volume (−1.2±1.3 mm 2 versus −1.1±0.8 mm 2 , P =0.452). Late stent malapposition was identified in 8 (13%) SES and 2 (3%) PES but in no ZES ( P =0.050). Angiographic restenosis was detected in 6 lesions (3 PES and 3 ZES). Conclusions— The degree of neointimal growth in ZES was similar to that in PES but less than that in SES. ZES had no late stent malappositions. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00418067.

Relation between age and aortic wall compliance in the Marfan syndrome: evaluation with Velocity-Encoded MRI

MRI was performed on 1.5 T Philips Achieva MRI (Philips Medical Systems, Best, The Netherlands). PC-MRI with through-plane velocity encoding (Venc = 150 cm/s) and free-breathing was performed perpendicular to the ascending and descending aorta at the level transecting the pulmonary trunk. Another acquisition (Venc = 100 cm/ s) was performed at the abdominal aorta. PWV was determined for the aortic arch (AA), distal aorta (DA) and total aorta using the transit-time method described by Grotenhuis.1 Brachial-cuff systolic and diastolic blood pressure (BP) were obtained. Distensibility (= luminal area change/(diastolic luminal area × pulse pressure)) and Stiffness Index (= ln [(BPSystolic/BPDiastolic)/(diameter change/diastolic diameter)]) were determined at the ascending aorta in gradient-echo PC-MRI magnitude images. Reduced wall compliance is expressed as increased PWV and SI and decreased Dist. PWV, Dist and SI were compared in Marfan and controls using paired ttests. Age relation was determined by linear regression.

Impact of pioglitazone on coronary endothelial function in non-diabetic patients with coronary artery disease

Pioglitazone has been shown to exert multiple antiatherosclerotic actions independent from its glycemic effects. We studied the hypothesis that pioglitazone improves coronary endothelial dysfunction in non-diabetic patients with coronary artery disease (CAD) in a randomized, placebo-controlled, double-blind trial. Fifty non-diabetic patients with CAD were randomized to 6 months treatment with pioglitazone 30 mg daily or placebo. Coronary endothelial function was tested at baseline and after 6 months with intracoronary infusion of adenosine, acetylcholine (0.072; 0.72; 7.2, and 36 microg/min), glyceroltrinitrate, and cold pressor test (CPT). The primary endpoint was the mean effect of treatment compared with placebo on acetylcholine-induced coronary vascular response for all acetylcholine dosages, based on percent change in luminal area measured by quantitative coronary angiography. There was no difference in baseline coronary endothelial function. The primary endpoint was significantly different between the groups with a 1.8% +/- 2.0% increase in luminal area between baseline and follow-up with pioglitazone and a 7.6% +/- 2.4% decrease in the placebo group (P < 0.008). At follow-up, there was a trend for a difference in CPT (P = 0.057). No difference was observed regarding intracoronary glyceroltrinitrate or adenosine. Pioglitazone treatment in non-diabetic patients with CAD was associated with a significantly better coronary endothelial function compared to placebo.

Morphometric analysis of intimal thickening secondary to stent placement in pig carotid arteries

To evaluate intimal thickening secondary to stent placement or to insertion of the delivery system without stent placement in pig carotid arteries. Stents were placed in the right common carotid arteries of 7 pigs, and 7 other control pigs underwent only insertion of the delivery system without stent placement. Uninjured contralateral common carotid arteries of the two groups were also used as controls. Samples of arterial tissue, obtained from the area adjacent to the distal segment of the stent four weeks after placement, underwent morphometric analysis. Morphometric data were compared with findings for arterial samples from injured arteries of the control group and uninjured contralateral arteries of the two groups. The unpaired Mann-Whitney U test and the Wilcoxon t test for nonparametric samples were used for statistical analysis. Greater intimal thickening was found in the group in which stents were placed (p=0.008). Changes in luminal area and media layer were not significantly different between the two groups. The comparison of contralateral carotid arteries of the two groups revealed significant changes in intimal and luminal areas. No statistically significant changes were found in medial layer area. All arteries that underwent stent placement showed intimal thickening without changes in the tunica media at four weeks. Dissection and insertion of the delivery system without stent placement was associated with a lesser degree of intimal thickening.

The effects of inhaled corticosteroids on intrinsic responsiveness and histology of airways from infant monkeys exposed to house dust mite allergen and ozone

Inhaled corticosteroids (ICS) are recommended to treat infants with asthma, some with intermittent asthma. We previously showed that exposing infant monkeys to allergen/ozone resulted in asthma-like characteristics of their airways. We evaluated the effects of ICS on histology and intrinsic responsiveness of allergen/ozone-exposed and normal infant primate airways. Infant monkeys were exposed by inhalation to (1) filtered air and saline, (2) house dust mite allergen (HDMA) + ozone and saline, (3) filtered air and ICS (budesonide) or (4) HDMA + ozone and ICS. Allergen/ozone exposures started at 1 month and ICS at 3 months of age. At 6 months of age, methacholine-induced changes in luminal area of airways in proximal and distal lung slices were determined using videomicrometry, followed by histology of the same slices. Proximal airway responsiveness was increased by allergen/ozone and by ICS. Eosinophil profiles were increased by allergen/ozone in both proximal and distal airways, an effect that was decreased by ICS in distal airways. In both allergen/ozone- and air-exposed monkeys, ICS increased the number of alveolar attachments in distal airways, decreased mucin in proximal airways and decreased epithelial volume in both airways. ICS increased smooth muscle in air-exposed animals while decreasing it in allergen/ozone-exposed animals in both airways. In proximal airways, there was a small but significant positive correlation between smooth muscle and airway responsiveness, as well as between alveolar attachments and responsiveness. ICS change morphology and function in normal airways as well as allergen/ozone-exposed airways, suggesting that they should be reserved for infants with active symptoms.

THE ADENOSINE 2A RECEPTOR AGONIST ATL-146E ATTENUATES EXPERIMENTAL POSTHEMORRHAGIC VASOSPASM

Selective adenosine 2A receptor agonists, such as ATL-146e, are known to be potent anti-inflammatory agents devoid of systemic side effects and have been used clinically in a number of disease states. However, adenosine 2A receptor agonists have not been studied in the treatment of cerebral vasospasm after subarachnoid hemorrhage. The present study investigated the efficacy of ATL-146e in the prevention of leukocyte infiltration and attenuation of posthemorrhagic vasospasm. The rodent femoral artery model of vasospasm was used. Forty male Sprague-Dawley rats were randomly assigned to four different groups (vehicle, 1 ng/kg/min, 10 ng/kg/min, or 100 ng/kg/min ATL-146e administered via subcutaneous osmotic minipump). Vasospasm was evaluated at posthemorrhage Day 8 (period of peak constriction) by calculating the lumen cross-sectional area (expressed as percent change in luminal area: ratio of blood-exposed vessel to normal saline-exposed vessel) and radial wall thickness. Immunostaining with anti-CD45 monoclonal antibody to detect leukocytes was used to evaluate localized inflammation. Significant vasospasm was noted in the vehicle-treated (blood-exposed) control group (78.5%, P < 0.001; expressed as a ratio of luminal area of the saline [no blood] control), but not in the ATL-146e-treated groups (lumen ratio to control: 105.0, 83.4, and 91.3% for the 1, 10, and 100 ng/kg/min groups, respectively). Additionally, infiltration of inflammatory cells was reduced significantly and radial wall thickness was decreased in the ATL-146e-treated groups compared with the vehicle-treated control group. Selective activation of the adenosine 2A receptor with ATL-146e prevented posthemorrhagic vasospasm and reduced leukocyte infiltration in this experimental model. This agent is worthy of further investigation and lends credence to the hypothesis supporting a role for inflammation in the pathogenesis of cerebral vasospasm after subarachnoid hemorrhage.

Evaluation of manufacturing variability, diffusion of filling solutions, and long-term maintenance of occlusion in silicone hydraulic occluders

To evaluate manufacturing variability, diffusion of filling solutions, and maintenance of occlusion over time in 3 sizes of silicone hydraulic occluders (HOs). 2-, 5-, and 20-mm HOs (HO2, HO5, and HO20, respectively). Manufacturing variability was analyzed by comparing variation in internal luminal areas and filling volumes within each size group. Occluders were filled to 100% occlusion with air (n = 4), saline (0.9% NaCl) solution (4), or sodium hyaluronate (4) and submerged in simulated body fluid. Changes in luminal area and weight were recorded for 133 days to evaluate maintenance of occlusion. Considerable variability in uninflated luminal area and fill volumes was observed among the 3 sizes of HOs. Loss of occlusion developed in the first 12 hours in all air-filled HOs. Fluid-filled occluders were reliable in maintenance of occlusion after 133 days (99.99% for HO20, 99.59% for HO5, and 90.40% for HO2), although diffusion of saline solution and hyaluronate from all HOs was confirmed by detection of significant decreases in weight over time. There was no significant difference in weight loss between HOs filled with saline solution and HOs filled with sodium hyaluronate. Saline solution or sodium hyaluronate may be used as a filling solution in the HOs tested. Maintenance of occlusion was best in the larger sizes. Saline solution or sodium hyaluronate should be used in future clinical investigations of HOs. Retrograde filling to remove air should be used when filling HOs with fluid.

Changes of Aortic Morphology after Aortic Dissection Evaluated by CT Angiography

Background and Objectives:In aortic dissection (AD, CT angiography (CTA is useful both in initial dia- gnosis and long term follow-up. In this study, we used CTA to evaluate the morphologic changes of aorta after AD. Subjects and Methods:We reviewed the initial and follow-up CTA images of 43 patients with AD. The diagnoses were double-lumen dissection (n=13, intramural hematoma (n=11, and residual dissection after surgery (n=19. The duration of CTA follow-up was 3.3±1.9 years (range 7-89 months. After reviewing the CTA images of the thoracic aorta level, and of the upper and lower abdominal aorta levels, we compared the areas of total lumen, true lumen and false lumen and the area ratio of true/total lumen. Results:Changes in luminal areas were greatest in the thoracic aorta, where both the true lumen area and the ratio of true/total lumen area increased. Subgroup analysis revealed that although the total lumen area increased significantly in the classic AD group, no changes were noted in the ratio of true/total lumen area. Only the increase in false lu- men area (from 5.8 cm 2 to 9.0 cm 2 was significant (p=0.036. In patients with intramural hematoma, a decr- ease in total lumen area and an increase in the ratio of true/total lumen area were noted. Conclusion:In classic AD, false lumen dilatation occurs with false lumen enlargement, whereas in intramural hematoma total aorta size decreases with any increase in the ratio of true/total lumen area. ( ( ( (Korean Circulation J 2002;32(1 :53-60

NADH/NADPH oxidase p22 phox gene polymorphism is associated with improved coronary endothelial vasodilator function

The NADH/NADPH oxidase system plays a central role in vascular superoxide anion production, which appears to cause coronary endothelial dysfunction. Recently, it has been suggested that the C242T polymorphism of the NADH/NADPH oxidase p22 phox gene can reduce susceptibility to coronary artery disease. We therefore tested whether this polymorphism is associated with an altered endothelium-dependent vasodilator capacity of human coronary arteries in vivo. The vasodilator function of epicardial arteries in 93 patients was assessed by endothelium-mediated, flow-dependent dilation and nitroglycerin, which is endothelium-independent. NADH/NADPH oxidase p22 phox polymorphism was determined by restriction fragment length polymorphism. Carriers of the CC genotype of the C242T p22 phox polymorphism (n = 44) revealed a significantly blunted endothelium-dependent dilator response (11 +/- 9.2% luminal area change vs 17 +/- 10%;P = 0.007), which was, by multivariate analysis, independent of other risk factors or atherosclerosis itself. There was only a trend towards decreased endothelium-independent dilation in patients bearing the p22 phox CC genotype (P = 0.07). The C242T polymorphism of the p22 phox gene is an important independent determinant of coronary endothelial vasodilator function. These results provide the first clinical evidence for the functional significance of a polymorphism of a gene related to superoxide anion production in the vascular wall.

Accelerated intimal hyperplasia and increased endogenous inhibitors for NO synthesis in rabbits with alloxan-induced hyperglycaemia.

1. We examined whether endogenous inhibitors of NO synthesis are involved in the augmentation of intimal hyperplasia in rabbits with hyperglycaemia induced by alloxan. 2. Four weeks after the endothelial denudation of carotid artery which had been performed 12 weeks after alloxan, the intimal hyperplasia was greatly augmented with hyperglycaemia. The degree of hyperplasia was assessed using three different parameters of histopathological findings as well as changes in luminal area and intima: media ratio. 3. There were positive and significant correlations between intima:media ratio, plasma glucose, and concentrations of N(G)-monomethyl-L-arginine (L-NMMA) and N(G), N(G)-dimethyl-L-arginine (ADMA) in endothelial cells, that is, the intima:media ratio became greater as plasma glucose and endothelial L-NMMA and ADMA were increased. Furthermore, endothelial L-NMMA and ADMA were increased in proportion to the increase in plasma glucose. 4. In contrast, there were inverse and significant correlations between cyclic GMP production by carotid artery strips with endothelium and plasma glucose, between cyclic GMP production and endothelial L-NMMA and ADMA, and between the intima:media ratio and cyclic GMP production. 5. Exogenously applied L-NMMA and ADMA inhibited cyclic GMP production in a concentration-dependent manner. IC50 values were determined to be 12.1 microM for the former and 26.2 microM for the latter. The cyclic GMP production was abolished after the deliberate removal of endothelium from the artery strips. 6. These results suggest that the augmentation of intimal hyperplasia with hyperglycaemia is closely related to increased accumulation of L-NMMA and ADMA with hyperglycaemia, which would result in an accelerated reduction in NO production/release by endothelial cells.

Percutaneous transluminal coronary angioplasty reverses vasoconstriction of stenotic coronary arteries in hypertensive patients.

Endothelial dysfunction of coronary arteries with impaired vasodilation has been reported in patients with arterial hypertension. However, the effect of dynamic exercise on coronary vasomotion of a stenotic vessel segment before and after PTCA has not yet been evaluated in these patients. Coronary vasomotion of a normal and a stenotic vessel segment was studied in 39 patients with coronary artery disease during supine bicycle exercise before and 9+/-3 months after PTCA. Luminal area changes were determined by biplane quantitative coronary arteriography. There were 21 normotensive and 18 hypertensive patients who did not differ with regard to clinical characteristics. Percent area stenosis decreased after PTCA from 90% to 39% (P<0.001) in normotensive and from 86% to 33% (P<0.001) in hypertensive patients. Exercise-induced vasomotion of the normal vessel segment was significantly different between normotensives and hypertensives before (+19% versus +1%, P<0.01) and after (+16% versus +3%, P<0.01) PTCA. In contrast, stenotic vessel segments showed vasoconstriction in both normotensive and hypertensive patients (Deltaexercise, -11% versus - 20%, P=NS), which was reversed after PTCA (+3% versus +2%, P=NS). Normal coronary arteries show reduced vasodilation during exercise in hypertensive patients that may be explained by the presence of endothelial dysfunction. Stenotic vessels demonstrate paradoxical vasoconstriction during exercise in both normotensive and hypertensive patients. PTCA reverses vasoconstriction by elimination of the flow-limiting stenosis and prevention of coronary stenosis narrowing during exercise in normotensive and hypertensive patients.

Intravascular Ultrasonic Evidence for Importance of Plaque Distribution (Eccentric vs Circumferential) in Determining Distensibility of the Left Anterior Descending Artery

Although previous studies have shown that coronary atherosclerosis is accompanied by impaired vessel wall compliance, few data exist regarding the regional vessel distensibility that may be important in order to gain an insight into the mechanism of atherosclerotic plaque rupture. Therefore, we analyzed 45 coronary sites of the proximal left anterior descending artery from 40 patients. Using intravascular ultrasound, luminal area in diastole (A) and in systole was measured at the diseased sites. With the ratio of luminal area changes (dA) to coronary pressure changes (dP) during a cardiac cycle, the total distensibility index was obtained by the formula: [(dA/A)/dP] × 103. At the sites with noncircumferential disease perimeters in diastole (L) and in systole were measured at the normal and narrowed portions. Using the changes in perimeters (dL) during a cardiac cycle, the regional distensibility index was obtained by the formula: [(dL/L)/dP] × 103. In 22 sites with circumferential disease, the total distensibility index was 1.03 ± 0.61/mm Hg (mean ± SD), and significantly lower than that from 23 sites with noncircumferential disease that showed 1.45 ± 0.89/mm Hg (p <0.05). In noncircumferential disease, the regional distensibility index at narrowed portions was significantly lower, 0.33 ± 0.47/mm Hg, than that at normal portion, 1.11 ± 0.75/mm Hg (p <0.01), suggesting the heterogenous distribution of regional wall distensibility in noncircumferential lesions. These results indicate that the heterogeneous regional wall distensibility exists at the sites with noncircumferential disease where the total vessel distensibility is preserved by the presence of the compliant normal portion.To examine the heterogeneity of coronary distensibility at the sites with noncircumferential atherosclerotic disease, regional wall distensibility was determined by intravascular ultrasound. The regional distensibility index at the diseased portion was significantly lower than that at normal portions, suggesting the presence of the heterogeneous regional wall distensibility in noncircumferential disease; this may explain in part the plaque disarrangement that mainly occurs at the shoulder of the disease sites in noncircumferential disease.

Effect of lung inflation and airway muscle tone on airway diameter in vivo.

How normal airway dimensions change with lung volume is of great importance in determining flow limitation during the normal forced vital capacity maneuver as well as in the manifestation of obstructive lung disease. The literature presents a confusing picture, with some results suggesting that airway diameter increases linearly with the cube root of lung volume and others showing a highly nonlinear relation. The effect of smooth muscle contraction on lung-airway interdependence is even less well understood. Recent morphological work explicitly assumes that airway basement membrane is nondistensible, although the lung volume at which this maximal airway size is reached is unknown. With smooth muscle contraction, folding of the epithelium and basement membrane accounts for the changes in luminal area. In this study, we measured the effect of lung inflation on relaxed and contracted airway areas by using high-resolution computed tomography at different transpulmonary pressures, each held for 2 min. We found that fully relaxed airways are quite distensible up to a pressure of 5-7 cmH2O (P < 0.001), where they reach a maximal size with no further distension up to an airway pressure of 30 cmH2O (P = 0.49). Thus relaxed airways clearly do not expand isotropically with the lung. With smooth muscle tone, the airways in different animals responded differently to lung inflation, with some animals showing minimal airway dilation up to an airway pressure of 20 cmH2O and others showing airways that were more easily dilated with lung expansion. However, maximal diameter of these moderately constricted airways was not usually achieved even up to an airway pressure of 30 cmH2O. Thus a transient deep inspiration in vivo would be expected to have only a small effect on contracted airways.

Normalization of abnormal coronary vasomotion by calcium antagonists in patients with hypertension.

Endothelial dysfunction with a loss of endothelium-dependent vasodilation has been reported in patients with arterial hypertension. The purpose of the present study was to evaluate coronary vasomotor response to dynamic exercise in patients with coronary artery disease with and without arterial hypertension and to determine the effect of calcium antagonists on coronary vasomotion. Cross-sectional areas of a normal and a stenotic coronary vessel segment were examined in 79 patients with coronary artery disease at rest and during supine bicycle exercise (Ex). Change in luminal area after acute administration of a calcium antagonist (diltiazem or nicardipine), during exercise, and after sublingual nitroglycerin (percent change compared with rest = 100%) was assessed by biplane quantitative coronary arteriography. Patients were divided into two groups: Group 1 (control) consisted of 48 patients without (normotensive subjects, n = 30; hypertensive subjects, n = 18) and group 2 of 31 patients with (normotensive subjects, n = 15; hypertensive subjects, n = 16) pretreatment with a calcium antagonist immediately before exercise. The groups did not differ with regard to clinical characteristics or hemodynamic data measured during exercise. Mean aortic pressure at rest, however, was significantly increased in hypertensive patients compared with normotensive subjects in group 1 (103 mm Hg versus 92 mm Hg, P < .01) and group 2 (110 mm Hg versus 98 mm Hg, P < .025). In group 1, exercise-induced vasomotor response was significantly different between normotensive and hypertensive patients in normal (+20% versus +1%, P < .003) and stenotic vessels (-5% versus -20%, P < .025). However, in group 2 there was coronary vasodilation in normotensive and hypertensive patients for both normal (delta Ex +23% versus +21%, P = NS) and stenotic vessel segments (+24% versus +26%, P = NS). Abnormal coronary vasomotion during exercise can be observed in hypertensive patients with reduced vasodilator response in normal arteries and enhanced vasoconstrictor response in stenotic arteries. Calcium antagonists prevent the abnormal response of normal and stenotic coronary arteries to exercise in hypertensive patients and thus may compensate for endothelial dysfunction with reduced vasodilator response to exercise.

Dynamic expansion of the coronary arteries: Implications for intravascular ultrasound measurements

The majority of coronary artery blood flow occurs in diastole; however, systolic epicardial coronary artery expansion has been described. With the advent of intravascular ultrasound, precise measurements of arterial structures with excellent spacial and temporal resolution are now readily available. However, the effect of dynamic expansion of the coronary arteries on routine intravascular ultrasound measurements has not been assessed. The purpose of this study was to determine in vivo the presence, timing, and extent of dynamic changes in the coronary arteries and saphenous vein grafts and to assess their implications for intravascular ultrasound measurements. Intravascular ultrasound images were obtained with simultaneous electrocardiographic monitoring in 202 coronary artery and 50 saphenous vein graft sites in 32 patients with varying plaque burden and morphologic features. Arterial, luminal, and plaque area were measured at end-diastole and early, mid-, and end-systole. Coronary luminal diameter increased 2.1%; luminal area increased 8.1%; arterial area increased 3.7%; and plaque area decreased 4.9% during mid and late systole ( p < 0.01). There was no detectable cyclic change in saphenous vein graft dimensions. In coronary arteries there was significant systolic expansion of the artery and lumen and systolic thinning of the plaque. The magnitude of dynamic luminal area change was greater than the variability in measurement and thus warrants gating to the cardiac cycle. The lack of dynamic change in saphenous vein grafts and the relatively small dynamic change in luminal diameter and arterial and plaque areas suggest nominal utility in gating these measurements to the cardiac cycle.

Assessment of Coronary Artery Distensibility by Intravascular Ultrasound

Atherosclerotic change in the coronary artery is associated with an impaired vessel wall distensibility. However, there are few data regarding the relation between vessel wall morphology and distensibility. Therefore, with intravascular ultrasound, we assessed coronary artery distensibility in angiographically normal coronary segments of humans. Data were analyzed at 35 angiographically normal coronary sites where circumferential or noncircumferential lesions were demonstrated by ultrasound in 22 patients (mean age, 55 years). After intracoronary injection of 500 micrograms nitroglycerin (NTG), coronary luminal area was measured with intravascular ultrasound (30 MHz, 3.5F to 4.3F, 1800 rpm). Intracoronary pressure was simultaneously measured with a 2F micromanometer-tipped catheter located at the left main coronary artery. The coronary distensibility index was calculated as 10-fold the ratio of luminal area change to intracoronary pressure change during a cardiac cycle. Another pressure-independent vascular stiffness index, beta, was derived by the following formula: beta = [ln(SBP/DBP)]/(dD/diastolic mean diameter), where SBP is systolic intracoronary pressure, DBP is diastolic intracoronary pressure, and dD is the difference between systolic and diastolic diameters. At the sites where luminal areas were measured, thickness of intima-media complex, defined as the distance between the intimal leading edge and the adventitial leading edge, was determined as an index of the severity of atherosclerosis. In seven segments, distensibility index was determined before and after NTG injection to examine the effect of NTG on coronary distensibility. In all examined sites, including circumferential and noncircumferential lesions, the luminal area was 12.6 +/- 5.0 mm2 during systole and 11.6 +/- 4.6 mm2 during diastole, and the calculated coronary distensibility index ranged from 0 to 0.83 mm2/mm Hg. The thickness of the intima-media complex ranged from 0.12 to 1.30 mm, suggesting the presence of various grades of atherosclerosis even in the absence of angiographic lesions. There was a poor inverse correlation between thickness of the intima-media complex and distensibility index (r = .19, y = -0.17x + 0.41, P = .29). However, when noncircumferential lesions were excluded for evaluation, there was a significant inverse correlation between them (r = .58, y = -0.50x + 0.72, P < .01). Under these conditions, the thickness of the intima-media complex also correlated with the value of beta (X10(-1), which ranged from 0.28 to 3.99 (r = .70). After NTG injection, coronary distensibility increased by an average of 71% in the segments with a thin intima-media complex, whereas it did not substantially change in those with a relatively thick intima-media complex. These results suggest that coronary distensibility is impaired in the coronary sites accompanying occult atherosclerosis, none of which can be detected by the conventional angiography. NTG can augment coronary distensibility in the segments without a markedly thickened intima-media complex. We suggest that thickness of the intima-media complex can contribute to determining the coronary distensibility in clinical settings.