Decrease In Luminal Area Research Articles

Abstract 19038: Insights of Optical Coherence Tomography Into the Safety and Efficacy of Coronary Intravascular Lithotripsy for Calcified Nodule Modification During Percutaneous Coronary Intervention

Background: Among calcified lesions, nodular calcium is the most challenging subset to deal with during percutaneous coronary intervention (PCI), as there are limited options available for its modification. This study was done to assess the safety, efficacy and impact of coronary intravascular lithotripsy (IVL) on calcified nodule (CN) using optical coherence tomography (OCT). Methods: A total of 17 patients with 40 CN undergoing PCI using coronary intravascular lithotripsy were prospectively enrolled in the study. OCT parameters studied were pre-IVL minimum lumen area (MLA), calcium (Ca) score, number of CN, proximal and distal reference diameter, post-IVL gain in MLA, calcium fracture, major dissection, post-PCI minimum stent area (MSA), stent expansion, apposition, edge dissection and spherical index at CN. Spherical index was calculated by dividing the shortest and longest diameter at CN after stent placement. The primary safety endpoint was freedom from major adverse cardiovascular events (death, MI and target vessel revascularization) during hospitalisation and at 30 days. Primary efficacy endpoints were gain in MLA after stent placement and stent expansion. Results: Pre-IVL mean MLA at CN was 3.87±2.25mm 2 , Ca score was 3.94±0.24, Ca arc 190.59±54.02 o , Ca depth 0.97±0.31mm, Ca length 22.73±9.87mm and CN height-1.04±0.30 mm. All 17 (100%) patients developed Ca fractures, post-IVL MLA at CN was 5.20±2.31mm 2 , CN height 0.83±0.19mm and luminal gain at CN was 0.76 ± 1.71mm 2 . 10 (58.8%) patients developed fractures at base of CN and rest developed fractures at apex. Patients with fractures at base showed decrease in luminal area after IVL due to luminal shift of nodule, but all these patients had good stent expansion, likely due to Ca softening. Post-IVL OCT showed minor dissections in 5 (29.4%) and major in 3 (17.6%) patients. There was no perforation, slow flow or abrupt vessel closure. Stent expansion and MSA at CN was 107.12 ± 18.98% and 8.57±2.54 mm 2 respectively with spherical index of 0.83±0.12. All patients were free of MACE during hospitalization and at 30 days. Conclusion: Coronary intravascular lithotripsy is safe and effective for modification of coronary calcified nodules during percutaneous coronary intervention.

Dysfunction of Vascular Smooth Muscle and Vascular Remodeling by Simvastatin

Statins, inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A reductase, are widely prescribed for hypercholesterolemia. With the increasing use of statins, numerous reports demonstrated that statins can cause damage to skeletal muscles. However, the toxicities of statins on vascular smooth muscle, which are essential to cardiovascular homeostasis, have not been previously described. Here, we examined the effects of simvastatin on the contractile function and the integrity of vascular smooth muscle in isolated rat thoracic aortic rings, primary cultured vascular smooth muscle cells (VSMCs) in vitro and rats in vivo. In aortic rings, simvastatin suppressed the normal agonist-induced contractile responses in time- and concentration-dependent manners (0.86 g ± 0.11 at 10 μM simvastatin for 24 h compared with 1.89 g ± 0.11 at control). The suppression persisted in the endothelium-denuded aortic rings and was irreversible even after wash-out of simvastatin. Simvastatin suppressed the contraction induced by Bay K8644, an activator of voltage-operated Ca²⁺ channel (VOCC) in rat aortic rings and abolished agonist-induced intracellular Ca²⁺ increase in VSMCs. The simvastatin-induced contractile dysfunction was reversed by the supplementation of mevalonate and geranylgeranylpyrophosphate, precursors for protein isoprenylation. Consistently, activation of RhoA, a representative isoprenylated protein, was disrupted by simvastatin in VSMCs and RhoA-mediated phosphorylation of MYPT1 and CPI-17, and tonic tension were also suppressed. Notably, prolonged treatment of simvastatin up to 48 h induced apoptosis of vascular smooth muscle in aortic rings. Most importantly, simvastatin treatment in vivo significantly attenuated the agonist-induced vasoconstriction in rats ex vivo and induced a decrease in luminal area of the vascular wall. Collectively, these results demonstrate that simvastatin can impair the normal vascular contractility by disturbing Ca²⁺ influx and RhoA activity, ultimately leading to apoptosis and structural remodeling.

Paradoxical changes in lumen size during progression and regression of carotid atherosclerosis

Summary Atherosclerotic changes regarding the lipid pool and frbrous cap are related to the lumen and show countgerintuitive changes; a discourse on Glagov’s Hypothesis. Background Relative changes in arterial lumen size during progression and regression of atherosclerosis particularly in response to lipid modulating therapy are largely unknown. This study was designed to investigate the effects of statin therapy on human carotid atherosclerotic lesions as measured by high-resolution Cardiac Magnetic Resonance (CMR). Methods Via CMR (1.5T GE, WI), 35 carotid arteries of 18 asymptomatic, ‘statin naive’ patients with maximum carotid stenosis >50% (mean 64±21), were imaged at baseline and following 12 months of randomized, blinded statin therapy (simvastatin 40mg or Vytorin (Ezetimibe 10mg/ simvastatin 40mg)). The effects of statins on these lesions were evaluated as changes in carotid outer wall area (OWA), lumen area (LuA), vessel wall area (VWA), lipid area (LpA) and lipid percentage (Lp%). The percentage of stenosis of each slice was determined in reference to a normal or near normal sl. Results A total of 707-2mm slices of interpretable quality were available representing 39 in vivo plaques. Among these as followed over time, 378 (53.5%) demonstrated progression while 329 (46.5%) showed regression. Among ‘Progressors’, OWA, VWA, Lp% and LuA increased (P< .001 for OWA, VWA and Lp% and 0.14 for LuA), while among ‘Regressors’, all the above parameters decreased significantly (P<.001 for all). There was no statistically significant change in any of the parameters when all contiguous slices of all carotid plaques were analyzed in a 3D fashion. Conclusions Changes in carotid plaque after lipid lowering therapy, as measured by high-resolution CMR depict a counterintuitive effect on lumen size: as VWA and LpA decrease so does the LuA. Similarly, as VWA and LpA increase so does LuA. The measurement of luminal area may not be ar eliable measure of response of carotid plaque to statin therapy, as progression of carotid atherosclerosis is associated with a paradoxical increase and regression of atherosclerosis with a paradoxical decrease in luminal area. Funding Internal.

Two-Year Clinical Outcome after Carvedilol-Loaded Stent Implantation in Patients with Coronary Artery Disease

Background/AimsCarvedilol is an antioxidant that inhibits smooth muscle cell proliferation and migration. The aim of this study was to investigate the beneficial effects of carvedilol-loaded stents on 2-year clinical outcomes after stent implantation in patients with coronary artery disease.MethodsWe performed a prospective trial with male subjects to compare the safety and effects of carvedilol-loaded BiodivYsio® stents implanted into 20 patients with those of bare-metal BiodivYsio® stents implanted into 21 patients for de novo coronary lesions. The primary end point was the degree of neointimal hyperplasia, which was measured by intravascular ultrasound (IVUS) 6 months after the procedure; the secondary end point was major adverse cardiac events (MACE) at 2 years after implantation. All carvedilol and control stents were deployed successfully.ResultsA 2-year follow-up was completed for 19 patients (95%) in the carvedilol stent group and 20 patients (95%) in the control stent group. IVUS showed a trend toward a larger luminal area (6.86 ± 2.59 vs. 5.47 ± 1.52 mm2, p = 0.267), smaller neointimal area (1.34 ± 0.70 vs. 2.40 ± 1.73 mm2, p = 0.18), and reduced net decrease in luminal area (-0.78 ± 0.97 vs. -1.89 ± 1.78 mm2, p = 0.106) in the carvedilol stent group compared with the control stent group, respectively. There were no significant differences in the incidence of MACE (10.5 vs. 30.0%, respectively, p = 0.132) between the groups at 2 years after stent implantation. Stent thrombosis did not occur in either group after 2 years.ConclusionsThe carvedilol-loaded stents tended to inhibit neointimal hyperplasia without the occurrence of cardiac death, myocardial infarction, or stent thrombosis at 2-year follow-up.

Quantitative Analyses of Vitrified Autologous Venous Arterial Bypass Graft Explants

The purpose of this study was to compare vitrified small diameter venous arterial bypass graft explants with fresh graft controls using quantitative morphometrics and smooth muscle physiology. Fresh and vitrified reversed ipsilateral external jugular veins were used as autologous common carotid interposition bypass grafts on the right side in New Zealand White rabbits. Animals were sacrificed at either 2 or 4 weeks after implantation, and the vein grafts were harvested for study. Histology revealed that the vitrified grafts initially arteriolized more slowly than untreated grafts and that they caught up by 4 weeks postimplantation. Histomorphometrics revealed that the intimal area was less in vitrified grafts at 2 weeks (p = 0.007) and that the luminal area was less in vitrified grafts at 4 weeks (p = 0.002). All other morphometric parameters were not significantly different. Smooth muscle physiology demonstrated a tendency for the responses of vitrified grafts to be lower than controls, not statistically significantly different to controls for three of the four contractile agonists at each time point or for relaxation induced by acetycholine. Sodium nitroprusside-induced relaxations appeared to be identical. Sensitivity to histamine was decreased at 2 weeks, and the sensitivity to norepinephrine was increased at 4 weeks in vitrified explants (<0.05). This study demonstrates that vitrification slows down the arterialization process; however, by the end of the month after implantation the vein grafts have similar smooth muscle functions and histology. The greatest concern regarding use of this method for preservation of blood vessels for clinical application was the statistically significant decrease in luminal area observed at 1 month. Longer term in vivo studies are required to determine whether or not the observed luminal decrease progresses to occlusion.

Abnormalities of the Bronchial Arteries in Asthma

The bronchial arteries supply systemic blood to the airways, tracheobronchial lymph nodes, and nerves. Their structure has not been studied in patients with asthma. Case-control study of pathologic changes of bronchial arteries in asthma. Postmortem lungs were examined from three case groups: (1) fatal asthma (n = 12), death due to asthma; (2) nonfatal asthma (n = 12), asthmatic and death due to nonrespiratory causes; and (3) nonasthmatic control subjects (n = 12), no history of asthma and death due to nonrespiratory causes. In bronchial arteries with outer diameters of 0.1 to 1.0 mm, the areas of lumen, intima, and media were measured and compared between case groups. There were no significant differences in artery size (outer diameter) or in medial area between the three groups. In the two asthma groups, the intimal area was increased (p < 0.05), with a corresponding decrease in luminal area compared with the control group. There was a significant effect of gender, age, and smoking on intimal area. In the asthma cases, the area of bronchial artery intima was related to duration of asthma (p < 0.05), and this increase was associated with smooth muscle proliferation, reduplication, and calcification of the elastica, but not with inflammatory cell infiltration. While the pathophysiologic significance of these changes is uncertain, the relation to duration of asthma, age, and smoking suggests a secondary response to chronic airway disease.

Characterization of Coronary Atherosclerotic Plaques by Multidetector Computed Tomography

Multidetector computed tomography (MDCT) provides 3-dimensional noninvasive visualization of the coronary arterial tree. We compared MDCT with intravascular ultrasound (IVUS) for assessment of severity of coronary artery stenosis and composition of atherosclerotic plaques in 40 patients (32 men; mean age 52 years, range 33 to 86) with documented coronary artery disease. Cross-sectional images obtained at 10-mm increments were assessed for percent decrease in luminal area. Atherosclerotic plaques were classified by IVUS as soft, fibrous, or calcified. On the matched multidetector computed tomograms, regions of interest of 1 to 3 mm in diameter were placed inside each plaque, and tissue contrast was measured in Hounsfield units. Obstructive coronary artery disease was found in 50 segments by IVUS and 57 segments by MDCT. Sensitivity for detecting obstruction >50% was 86.0% (95% confidence interval 72.6 to 93.7) and specificity was 90.2% (95% confidence interval 83.9 to 94.4). In total, 276 plaques were examined by IVUS and MDCT. There were 188 soft plaques (68.2%), 45 fibrous plaques (16.2%), and 43 calcified plaques (15.5%). Multidetector computed tomographic tissue contrast of soft, fibrous, and calcified plaques were 71.5 +/- 32.1, 116.3 +/- 35.7, and 383.3 +/- 186.1, respectively (p <0.001). Using a cut-off value of 185 HU, 273 of 276 plaques (99%) were correctly classified as calcified or noncalcified plaques. Using a cut-off value of 88 HU, 192 of 233 noncalcified plaques (82%) were correctly classified as fibrous or soft plaques. In conclusion, our data indicate that MDCT can provide important information concerning the composition of atherosclerotic plaques in addition to detecting luminal obstruction.

Evaluation of the Characteristics of Venous Occlusion After Placement of an Ameroid Constrictor in Dogs

To evaluate the mechanism of vascular occlusion after placement of an ameroid constrictor (AC) on a large intra-abdominal vein and document changes in blood flow. Experimental study. Six adult dogs. Six 6.5 mm ACs were digitally scanned to measure area and circumference of the ameroid and inner lumen before surgery. ACs were surgically positioned around the left common iliac vein (CIV) in each dog. Peri-vascular ultrasonic flow probes were positioned on the left CIV cranial to the AC, and on the right CIV as an internal control. Blood flow measurements were recorded daily until there was no, or prolonged minimal, blood flow, at which time the dogs were euthanatized. Left and right CIVs were removed for histologic evaluation, and the ACs re-scanned to evaluate degree and direction of expansion of the ameroid. Reduction in blood flow occurred within 10 days in all dogs. Three dogs had complete occlusion by day 10 from thrombus formation. One dog damaged the flow probes at 13 days when blood flow was approximately 50% of intra-operative values; the dog was euthanatized at 37 days; there was partial occlusion from thrombosis. Two dogs had persistent low blood flow and occlusion from thrombus formation when euthanatized at 59 and 98 days. There was a significant increase in total AC area and outer circumference, and decrease in luminal area and inner circumference when presurgical and postocclusion measurements were compared. Vascular occlusion after placement of an AC on a large intra-abdominal vein occurred from thrombus formation. A similar pattern of venous occlusion may occur after placement of an AC on a portosystemic shunt, which may lead to both short- and long-term complications associated with portal hypertension.

Relative contributions of intimal hyperplasia and vascular remodeling in early cardiac transplant-mediated coronary artery disease

The relative contribution of intimal hyperplasia and vascular remodeling in early transplant coronary artery disease (TxCAD) is unknown. This study was designed to determine the contributions of vascular remodeling and intimal hyperplasia in the initial year after transplantation by intravascular ultrasound (IVUS). Twenty-five patients underwent baseline (<6 weeks after transplant) and 1-year angiography and IVUS to evaluate total vessel, luminal, and intimal + medial areas in ≥3 segments of the coronary artery. Nine patients had donor atherosclerotic disease on baseline study (23% of segments), and at 1-year, 21 patients (84%) had intimal hyperplasia (70% of segments). Fourteen patients had positive remodeling in all arterial segments, whereas the remaining 11 had positive and negative remodeling in the same vessel. Mean plaque area and total vessel area increased significantly (p = 0.0001) in proximal, mid, and distal segments, whereas total vessel area was most pronounced in distal segments. Luminal area did not change over time. Of the 87 segments evaluated, 68 (78%) had an increase in total vessel area, 57 (66%) had intimal growth, and 54 (62%) had an increase in luminal area. Although changes in total vessel and luminal area were closely correlated, a decrease in luminal area was associated with positive and negative remodeling. In conclusion, luminal area is generally maintained during the initial transplant year despite significant intimal hyperplasia due to positive remodeling. Reduction in the luminal area results from either inadequate positive remodeling or negative remodeling without intimal growth and often occurs in the same artery.

Quantitative Assessment of Airway Remodeling Using High-Resolution CT

Asthma and COPD are the most prevalent of lung diseases and contribute an enormous burden of morbidity in North America and globally. In both conditions, inflammation leads to airway remodeling, which contributes to airway narrowing. To date, airway remodeling has only been assessed using histological examination of airways. However, it may now be possible to assess and quantify the extent of airway remodeling in vivo using high-resolution CT (HRCT). The aim of this article is to review the use of HRCT in the investigation of airway remodeling. A number of investigators have reported techniques to make measurements of airway dimensions using CT and an increasing number of quantitative methods are being developed. Using these techniques, airway dimensions have been examined in patients with asthma and COPD. In patients with asthma, the airway wall area was increased without a decrease in luminal area, whereas in patients with COPD, the airway luminal area was decreased and airway wall area was increased. The different pattern of remodeling may reflect fundamental differences in the inflammatory processes in asthma and COPD and could influence the reversibility of the narrowing. It has also been shown that, by quantifying both the extent of emphysema and of airway remodeling, CT is useful in differentiating COPD patients who have primarily parenchymal disease from those who have primarily airway pathology. With additional advances in technology, it is likely that quantitative assessment of airway wall dimensions will ultimately provide a valuable tool for the study of airway disease.

Effects of bronchial vascular engorgement on airway dimensions.

Airway vascular engorgement has been suggested to cause luminal narrowing and airflow obstruction. To determine the extent to which changes in bronchial vascular volume could influence airway dimensions, we studied the effects of left atrial pressure elevation on airway morphometry in sheep (n = 17). The bronchial branch of the bronchoesophageal artery was cannulated and perfused with autologous blood (0.6 ml.min-1.kg-1). A balloon-tipped catheter was inserted into the left atrial appendage to elevate left atrial pressure by 10 mmHg, and papaverine was infused into the bronchial artery to eliminate airway smooth muscle tone. Morphological measurements were made from rapidly frozen lungs excised in vivo. Left atrial pressure elevation caused a 79% increase in total vascular area (P = 0.0002). Average airway luminal area was significantly decreased from 86 to 71% of the airway maximal area (P < 0.0001). Noteworthy were the prominent bronchial vessels located within mucosal folds. However, when papaverine was infused during left atrial pressure elevation, despite a comparable total vascular area, luminal narrowing did not occur and remained at 87% of the maximal area (P = 0.6267). In conclusion, we found that engorgement of the bronchial vasculature leads to an increase in the vascular area in regions inside and outside the smooth muscle layer. The associated decrease in luminal area only occurs in the presence of airway smooth muscle tone. This suggests a reflex effect on the airway caused by the vascular engorgement. We conclude that vascular engorgement of the airway wall per se has a negligible effect on airway obstruction.

Assessment of agonist- and cell-mediated responses in airway microsections by computerized videomicrometry

The objective of this investigation was to develop a method for real-time measurement of changes in luminal area in microexplants of airways during pharmacological and physiological interventions. After guinea pigs were killed, tracheal rings (1- to 2-mm thick) were excised and placed in 300-microliters chambers. The area of the airway lumen was calculated as pixel number with the use of computerized videomicrometry. In 29 epithelium-intact airways, 10(-3) M acetylcholine (ACh) caused decrease in luminal area of 38.1 +/- 2.80% (P < 0.001 vs. 10(-9) M). Spontaneous tone also was demonstrated in 34 preparations from 4 guinea pigs; decrease in area of 17.0 +/- 1.45% after 60-min incubation in buffer alone was blocked completely by 10(-5) M indomethacin (P = 0.01). Luminal narrowing caused by < or = 10(-6) M ACh was reversed completely by 10(-6) M albuterol (P = 0.002). Addition of 100,000 activated human eosinophils caused 24.7 +/- 4.41% decrease in luminal area vs. 7.24 +/- 5.51% for nonactivated cells (P = 0.048). We demonstrate a real-time method for the assessment of auxotonic changes in airway caliber that utilizes microsections of explanted airways and permits the use of extremely small numbers of isolated cells to achieve physiological activation. Concentration-response characteristics and spontaneous tone are similar to those of large chamber preparations, and narrowing is reversed by beta 2-adrenoceptor activation.

Paradoxical Arterial Wall Shrinkage May Contribute to Luminal Narrowing of Human Atherosclerotic Femoral Arteries

This study was done to assess how local changes in vessel size, together with plaque load, determine luminal narrowing in atherosclerotic arteries. Fifty-one human femoral arteries were analyzed: 32 postmortem and 19 in vivo by 30-MHz intravascular ultrasound. Histological and intravascular ultrasound cross sections were examined every 0.5 cm over an arterial segment 10 to 15 cm long. In each cross section we measured the lumen area and the area circumscribed by the internal elastic lamina (the IEL area). In each arterial segment, the cross section that contained the least amount of plaque was the reference site. For each cross section, the lumen area stenosis was expressed as percent of the lumen area in the reference site. Similarly, the IEL area was expressed as percent of the IEL area in the reference site (the relative IEL area). There was a significant negative correlation between the relative IEL area and the lumen area stenosis percentage (r = -.62, P < .001 for histology and r = -.66, P < .001 for intravascular ultrasound). When lumen area stenosis was less than about 25%, mainly compensatory enlargement was observed. When lumen area stenosis exceeded about 25%, however, mainly a decrease of the IEL area was observed, which is consistent with arterial wall shrinkage. Furthermore, the increase in plaque area does not account for the total loss of luminal area. There was a moderate correlation between an increase in plaque area and reduction of the corresponding lumen area (r = .49 and r = .56 for histology and intravascular ultrasound, respectively). The decrease in luminal area cannot be attributed to plaque increase alone. Arterial wall shrinkage is a paradoxical mechanism that may contribute to severe luminal narrowing of the atherosclerotic human femoral artery.

Vascular Remodeling in Coronary Artery Disease

Summary Traditionally, the diagnosis of significant coronary atherosclerotic disease has relied on angiographic techniques. Both histologic analyses and, more recently, intravascular ultrasonography techniques have revealed that a significant atherosclerotic plaque load may be present in epicardial coronary arteries without significant luminal narrowing, consistent with compensatory vessel enlargement or remodeling. In patients with coronary atherosclerosis, more limited structural changes are present in the smaller resistance arterioles, whereas a decrease in luminal area with an increase in wall thickness and perivascular fibrosis are the characteristic structural changes observed in resistance arteries in the presence of systemic hypertension. Further, functional changes, such as impairment of endothelium-mediated vasodilation, are present in epicardial and resistance vessels of patients with coronary atherosclerosis and may influence the progression of this disease and development of ischemic syndromes. The introduction of two-dimensional intravascular and Doppler ultrasonography enables us to study in vivo these morphologic and functional changes. In this article, the knowledge acquired in humans on the mechanisms and clinical relevance of vascular remodeling with the use of these two ultrasonography-based techniques is reviewed. The possibility of using pharmacologic interventions to improve or normalize the vascular response to endothelium-dependent and independent vascular interventions is discussed, with special attention to the efficacy of the inhibition of the angiotensin-converting enzyme.

A Vascular Protective Concept in Hypertension and

Traditionally, the diagnosis of significant coronary atherosclerotic disease has relied on angiographic techniques. Both histologic analyses and, more recently, intravascular ultrasonography techniques have revealed that a significant atherosclerotic plaque load may be present in epicardial coronary arteries without significant luminal narrowing, consistent with compensatory vessel enlargement or remodeling. In patients with coronary atherosclerosis, more limited structural changes are present in the smaller resistance arterioles, whereas a decrease in luminal area with an increase in wall thickness and perivascular fibrosis are the characteristic structural changes observed in resistance arteries in the presence of systemic hypertension. Further, functional changes, such as impairment of endothelium-mediated vasodilation, are present in epicardial and resistance vessels of patients with coronary atherosclerosis and may influence the progression of this disease and development of ischemic syndromes. The introduction of two-dimensional intravascular and Doppler ultrasonography enables us to study in vivo these morphologic and functional changes. In this article, the knowledge acquired in humans on the mechanisms and clinical relevance of vascular remodeling with the use of these two ultrasonography-based techniques is reviewed. The possibility of using pharmacologic interventions to improve or normalize the vascular response to endothelium-dependent and independent vascular interventions is discussed, with special attention to the efficacy of the inhibition of the angiotensin-converting enzyme.

Rabbit ear model of injury-induced arterial smooth muscle cell proliferation. Kinetics, reproducibility, and implications.

Recently, considerable interest has focused on the vascular smooth muscle cell (SMC) response to injury, particularly as it relates to restenosis after angioplasty. In an effort to find an optimal experimental model of arterial SMC proliferation after injury, we examined the effects of external injury to the central artery of the rabbit ear and assessed the reproducibility, morphological changes, and time course of cellular proliferation after such an injury. With rabbits under general anesthesia, direct pressure was applied at two sites along the central artery of the ears of 19 New Zealand White rabbits. Rabbits were maintained on a diet of 2.4% fat and 0.001% cholesterol throughout the experiment. In seven rabbits examined after 21 days, marked SMC proliferation with neointimal formation was observed at all 28 sites (100%). Mean neointimal area, expressed as a percentage of the area of the tunica media, was 82 +/- 40% (range, 21-203%). Compared with the uninvolved artery displaced 2 mm from the injury site, mechanical crush caused a 38% increase in total vessel area (p less than 0.001), a 40% decrease in luminal area (p less than 0.002), and no change in the area of the media. Serial histological studies were performed 1-42 days after injury, using light and electron microscopy and bromodeoxyuridine immunohistochemistry. Beginning at day 3, activated medial SMCs were noted to migrate through defects in the internal elastic membrane, with a gradual increase in neointimal area between days 5 and 12. Peak DNA synthesis was identified in the media 5 days after injury, with proliferative activity shifting almost exclusively to the neointima thereafter.(ABSTRACT TRUNCATED AT 250 WORDS)

The Effect of Nicardipine on Vasospasm in Rabbit Basilar Artery after Subarachnoid Hemorrhage

This study was performed to examine the effect of the dihydropyridine calcium antagonist, nicardipine, on vasospasm after experimental subarachnoid hemorrhage (SAH) in the rabbit. The study was carried out in two parts: 1) effect of intravenous nicardipine (n = 45) and 2) effect of intracisternal nicardipine (n = 21). SAH was induced by injecting 5 ml of autologous arterial blood into the cisterna magna. In the intravenous study, there were five groups: 1) SAH without treatment; 2) SAH with vehicle (saline); 3) SAH and intravenous infusion of low-dose incardipine (0.01 mg/kg/h); 4) SAH and intravenous infusion of high-dose nicardipine (0.15 mg/kg/h); and 5) controls without SAH. The intravenous infusions were started immediately after SAH and continued for 48 hours until death. In the intracisternal study, there were three groups: 1) SAH without treatment; 2) SAH with intracisternal administration of nicardipine (0.37 mg/h); and 3) controls without SAH. Intracisternal infusions were begun 70 hours after SAH and continued for 2 hours until death. After perfusion-fixation, the basilar artery was removed and processed for morphometric analysis. In the intravenous study, vessels from animals subjected to SAH were significantly narrowed when compared with controls, although after high-dose nicardipine vessel caliber was slightly larger than in the other SAH groups. Animals given intracisternal nicardipine showed a nonsignificant reduction of caliber as compared with controls: only 12% decrease in diameter and 22% decrease in luminal area. In the rabbit SAH model, nicardipine had a very modest effect on vasospasm at the doses tested. (Neurosurgery 29:183-188, 1991)

The effect of nicardipine on vasospasm in rabbit basilar artery after subarachnoid hemorrhage

This study was performed to examine the effect of the dihydropyridine calcium antagonist, nicardipine, on vasospasm after experimental subarachnoid hemorrhage (SAH) in the rabbit. The study was carried out in two parts: 1) effect of intravenous nicardipine (n = 45) and 2) effect of intracisternal nicardipine (n = 21). SAH was induced by injecting 5 ml of autologous arterial blood into the cisterna magna. In the intravenous study, there were five groups: 1) SAH without treatment; 2) SAH with vehicle (saline); 3) SAH and intravenous infusion of low-dose nicardipine (0.01 mg/kg/h); 4) SAH and intravenous infusion of high-dose nicardipine (0.15 mg/kg/h); and 5) controls without SAH. The intravenous infusions were started immediately after SAH and continued for 48 hours until death. In the intracisternal study, there were three groups: 1) SAH without treatment; 2) SAH with intracisternal administration of nicardipine (0.37 mg/h); and 3) controls without SAH. Intracisternal infusions were begun 70 hours after SAH and continued for 2 hours until death. After perfusion-fixation, the basilar artery was removed and processed for morphometric analysis. In the intravenous study, vessels from animals subjected to SAH were significantly narrowed when compared with controls, although after high-dose nicardipine vessel caliber was slightly larger than in the other SAH groups. Animals given intracisternal nicardipine showed a nonsignificant reduction of caliber as compared with controls: only 12% decrease in diameter and 22% decrease in luminal area. In the rabbit SAH model, nicardipine had a very modest effect on vasospasm at the doses tested.

Reversibility of Fixed Atherosclerotic Lesions with Aggressive Risk Factor Modification

Seven patients with atherosclerotic coronary artery disease documented by coronary angiography and exercise stress testing were treated with the American Heart Association Step II Diet, a walking program, and combination drug therapy with niacin, cholestyramine, gemfibrozil, and/or lovastatin. As a result of this intervention, there was a mean weight loss of 24.7 pounds, a mean reduction in cholesterol from 297 mg% to 167 mg%, a mean increase in high density lipoprotein cholesterol from 33 mg% to 55 mg%, and a mean reduction in triglyceride levels from 248 mg% to 58 mg%. Repeat exercise stress testing and coronary angiography were performed 2 years after the initial catheterization. Photographs of end-diastolic frames were compared utilizing the same views with the same magnification. In six of the seven patients, there was a mean increase in luminal area at the greatest stenosis of 1.3 mm2 in eight lesions present at initial catheterization. In four of these six patients, there was evidence for improvement in coronary blood flow manifested by improvement in electrocardiogram (ECG) exercise stress testing and/or exercise thallium stress testing. In one patient, there was a mean decrease in luminal area at greatest stenosis of 1.35 mm2 in two lesions and the development of an additional plaque in an area which was previously normal. In addition, this patient had evidence for progression by ECG exercise stress testing. Aggressive risk factor modification can reverse what were previously considered "fixed" atherosclerotic lesions in selected patients.

Effect of intravenous propranolol on coronary vasomotion at rest and during dynamic exercise in patients with coronary artery disease.

Coronary vasomotion was studied at rest and during bicycle exercise with biplane quantitative coronary arteriography in 28 patients with coronary artery disease. Patients were divided into two groups; the first 18 patients served as controls (group 1), and the next 10 patients were treated with propranolol 0.1 mg/kg, which was infused intravenously before exercise (group 2). Luminal area of a normal and a stenotic vessel segment was determined at rest, during supine bicycle exercise, and 5 minutes after sublingual administration of 1.6 mg nitroglycerin after exercise. In group 1, the normal vessel showed vasodilation (+16%, p less than 0.001) during exercise, whereas the stenotic vessel segment showed vasoconstriction (-31%, p less than 0.001). After sublingual administration of nitroglycerin, there was coronary vasodilation of both normal (+36%, p less than 0.001 vs. rest) and stenotic (+20%, p less than 0.001) vessel segments. Patients with angina pectoris during supine exercise (n = 10) had significantly (p less than 0.05) more vasoconstriction (-36%) than patients without angina (-23%). In group 2, intravenous administration of propranolol at rest was associated with a decrease in luminal area of both normal (-24%, p less than 0.001) and stenotic (-43%, p less than 0.001) vessel segments; however, during subsequent exercise, both normal (-2%, p = NS vs. rest) and stenotic (-3%, p = NS vs. rest) vessel segments dilated when compared with the measurements after propranolol. Administration of nitroglycerin further increased luminal area of both vessel segments (normal segment, +23%, p less than 0.001; stenotic segment, +46%, p less than 0.001 vs. rest). It is concluded that dynamic exercise in patients with coronary artery disease is associated with coronary vasodilation of the normal and vasoconstriction of the stenotic coronary arteries. Patients with exercise-induced angina had significantly more stenosis vasoconstriction than patients without angina although minimal luminal area at rest was similar. Intravenous administration of propranolol is accompanied by a significant decrease in coronary luminal area of both normal and stenotic vessel segments at rest, which is overridden by dynamic exercise and sublingual nitroglycerin. The reduction in myocardial oxygen consumption and the prevention of exercise-induced stenosis vasoconstriction might explain the beneficial effect of beta-blocker treatment in most patients with coronary artery disease.