Fatal right coronary artery rupture following blunt chest trauma: detection by postmortem selective coronary angiography.

Coronary artery injury is a rare complication following blunt chest trauma (BCT), and can be fatal. Here we report findings on postmortem selective coronary angiography of right coronary artery rupture after an assault involving blunt trauma to the chest. A woman in her 60s died after her son stomped on her chest. There were no appreciable signs of injury on external examination, and cause of death could not be determined by postmortem computed tomography (PMCT). Internal findings indicated that an external force had been applied to the anterior chest, as evidenced by subcutaneous hemorrhage and pericardial and cardiac contusions. Postmortem coronary angiography revealed irregularity of the intima and of the fat tissue surrounding the proximal part of the right coronary artery associated with a local filling defect. Histopathological examination suggested coronary rupture with dissection of the tunica media and compression of the lumen cavity. The key points in the present case are that no fatal injuries could be determined on external examination, and the heart and coronary artery injuries were not evident on PMCT. Criminality might be overlooked in such cases, as external investigation at the crime scene would be inadequate and could result in a facile diagnosis of cause of death. This is the first report of coronary artery rupture with dissection that was detected by CT coronary angiography, and provides helpful findings for reaching an appropriate decision both forensically and clinically.

Histopathological Evidence of Adventitial or Medial Injury Is a Strong Predictor of Restenosis During Directional Atherectomy for Peripheral Artery Disease.

PURPOSE: To investigate the impact on restenosis rates of deep injury to the adventitial layer during directional atherectomy. METHODS: Between 2007 and 2010, 116 consecutive patients (mean age 69.6 years; 56 men) with symptomatic femoropopliteal stenoses were treated with directional atherectomy at a single center. All patients had claudication and TASC A/B lesions in the superficial femoral or popliteal arteries. Histopathology analysis of atherectomy specimens was performed to identify adventitial injury. Clinical follow-up included physical examination and duplex ultrasound scans at 3, 6, and 12 months in all patients. The primary endpoint was the duplex-documented 1-year rate of restenosis, which was determined by a peak systolic velocity ratio <2.4. Patients were dichotomized by the presence or absence of adventitial or medial cuts as evaluated by histopathology. RESULTS: Adventitial injury were identified in 62 (53%) of patients. There were no differences in baseline demographic and clinical features (p>0.05), lesion length (58.7±12.8 vs 56.2±13.6 mm, p=0.40), or vessel runoff (1.9±0.6 vs 2.0±0.6, p=0.37) between patients with and without adventitial injury, respectively. The overall 1-year incidence of restenosis was 57%, but the rate was significantly higher (p<0.0001) in patients with adventitial or medial injury (97%, 60/62) as compared with those without (11%, 6/54). CONCLUSION: Lack of adventitial injury after atherectomy for femoropopliteal stenosis is strongly related to patency at 1 year.

Dynamic expressions of monocyte chemo attractant protein-1 and CC chamomile receptor 2 after balloon injury and their effects in intimal proliferation.

OBJECTIVE: The dynamic expressions of monocyte chemo attractant protein-1 (MCP-1) and CC chamomile receptor 2 (CCR2) after balloon injury and their effects in intimal proliferation were discussed. In this study, the expression of MCP-1 and its receptor during the intimal proliferation in rat artery after balloon injury were studied. METHODS: Using the model of balloon injury of rats' arteries, the changes of intimal proliferation were observed with optical microscopy and the expressions of MCP-1 and CCR2 at different times were examined with the methods of RT-PCR and immunohistochemistry. The expressions of MCP-1 and CCR2 in the arterial tissues were detected using reverse transcription polymerase chain reaction (RT-PCR) and analyzed by semi-quantitative method. RESULTS: The expressions of MCP-1 and CCR2 mRNA began to gradually increase after balloon injury. The MCP-1 reached to the peak on the first day, but decreased gradually later on. Expressions of CCR2 mRNA began to increase on the first day and reached to the peak on the 7th day, but then started to decrease gradually until 28th day when we can still detect it. The expressions of MCP-1 proteins began to increase gradually after balloon injury and were obviously detected in the VSMC on the 4th and 7th day, until 14th day when we can still detect it clearly in the proliferating intima. CONCLUSION: The dynamic expressions of MCP-1, MCP-1 proteins and CCR2 mRNA after balloon injury were shown to play an important role in intimal proliferation.

Systematic analysis of the radiologic findings of aortic dissections on unenhanced postmortem computed tomography.

The aim of this study was to evaluate the diagnostic criteria and to identify the radiological signs (derived from known radiological signs) for the detection of aortic dissections using postmortem computed tomography (PMCT). Thirty-three aortic dissection cases were retrospectively evaluated; all underwent PMCT and autopsy. The images were initially evaluated independently by two readers and were subsequently evaluated in consensus. Known radiological signs, such as dislocated calcification and an intimomedial flap, were identified. The prevalence of the double sedimentation level in the true and false lumen of the dissected aorta was assessed and defined as a postmortem characteristic sign of aortic dissection. Dislocated calcification was detected in 85% of the cases with aortic calcification; whereas in 54% of the non-calcified aortas, the intimomedial flap could also be recognized. Double sedimentation was identified in 16/33 of the cases. Overall, in 76% (25/33) of the study cases, the described signs, which are indicative for aortic dissection, could be identified. In this study, three diagnostic criteria of aortic dissection were identified using non-enhanced PMCT images of autopsy-confirmed dissection cases.

Apoptosis, paraptosis, necrosis, and cell regeneration in posttraumatic cerebral arteries.

This study is to understand the nature and functional significance of the activated cell death programs and rehabilitation signs during late vascular changes after brain injury. We used light and transmission electron microscopy to describe changes of cells within the vascular endothelium and tunica media of the cortical arteries four weeks after craniocerebral traumatism. Within tunica media of the posttraumatic damaged artery, apoptotic and paraptotic phenotypes were identified as well as some early ultrastructural signs of smooth muscle cells regeneration, these cell highlighting a remarkable degree of plasticity. Surprisingly, some endothelial cells showed an extensive rough endoplasmic reticulum development, whereas other endothelial cells showed typical necrosis. In conclusion, two groups of suicidal cells apoptotic and paraptotic cells were encountered in the same lesional vascular wall after neurotrauma, showing also signs of cell regeneration. The pathophysiologic significance of the coexisting double cell death programs and cell regeneration seems to be in relation with late cell survival, after arterial damage when some cells disappear and other cells try to survive undergoing reversible injury.

Epigenetic regulation of vascular smooth muscle cell proliferation and neointima formation by histone deacetylase inhibition.

OBJECTIVE: Proliferation of smooth muscle cells (SMC) in response to vascular injury is central to neointimal vascular remodeling. There is accumulating evidence that histone acetylation constitutes a major epigenetic modification for the transcriptional control of proliferative gene expression; however, the physiological role of histone acetylation for proliferative vascular disease remains elusive. METHODS AND RESULTS: In the present study, we investigated the role of histone deacetylase (HDAC) inhibition in SMC proliferation and neointimal remodeling. We demonstrate that mitogens induce transcription of HDAC 1, 2, and 3 in SMC. Short interfering RNA-mediated knockdown of either HDAC 1, 2, or 3 and pharmacological inhibition of HDAC prevented mitogen-induced SMC proliferation. The mechanisms underlying this reduction of SMC proliferation by HDAC inhibition involve a growth arrest in the G(1) phase of the cell cycle that is due to an inhibition of retinoblastoma protein phosphorylation. HDAC inhibition resulted in a transcriptional and posttranscriptional regulation of the cyclin-dependent kinase inhibitors p21(Cip1) and p27(Kip). Furthermore, HDAC inhibition repressed mitogen-induced cyclin D1 mRNA expression and cyclin D1 promoter activity. As a result of this differential cell cycle-regulatory gene expression by HDAC inhibition, the retinoblastoma protein retains a transcriptional repression of its downstream target genes required for S phase entry. Finally, we provide evidence that these observations are applicable in vivo by demonstrating that HDAC inhibition decreased neointima formation and expression of cyclin D1 in a murine model of vascular injury. CONCLUSIONS: These findings identify HDAC as a critical component of a transcriptional cascade regulating SMC proliferation and suggest that HDAC might play a pivotal role in the development of proliferative vascular diseases, including atherosclerosis and in-stent restenosis.

KIS protects against adverse vascular remodeling by opposing stathmin-mediated VSMC migration in mice.

Vascular proliferative diseases are characterized by VSMC proliferation and migration. Kinase interacting with stathmin (KIS) targets 2 key regulators of cell proliferation and migration, the cyclin-dependent kinase inhibitor p27Kip1 and the microtubule-destabilizing protein stathmin. Phosphorylation of p27Kip1 by KIS leads to cell-cycle progression, whereas the target sequence and the physiological relevance of KIS-mediated stathmin phosphorylation in VSMCs are unknown. Here we demonstrated that vascular wound repair in KIS-/- mice resulted in accelerated formation of neointima, which is composed predominantly of VSMCs. Deletion of KIS increased VSMC migratory activity and cytoplasmic tubulin destabilizing activity, but abolished VSMC proliferation through the delayed nuclear export and degradation of p27Kip1. This promigratory phenotype resulted from increased stathmin protein levels, caused by a lack of KIS-mediated stathmin phosphorylation at serine 38 and diminished stathmin protein degradation. Downregulation of stathmin in KIS-/- VSMCs fully restored the phenotype, and stathmin-deficient mice demonstrated reduced lesion formation in response to vascular injury. These data suggest that KIS protects against excessive neointima formation by opposing stathmin-mediated VSMC migration and that VSMC migration represents a major mechanism of vascular wound repair, constituting a relevant target and mechanism for therapeutic interventions.

Assessment of acute injuries and chronic intimal thickening of the radial artery after transradial coronary intervention by optical coherence tomography.

AIMS: Transradial coronary intervention (TRI) introduces a trauma to the radial artery (RA), possibly influencing quality as a bypass conduit if subsequently used. We sought to determine the acute and chronic effects of TRI on the RA by optical coherence tomography (OCT). METHODS AND RESULTS: Immediately after TRI completion, 73 RAs in 69 patients were examined. The sheath was pulled back 2 cm distal to the puncture site, and OCT imaging was performed. The acute injuries and intimal thickening were compared between first-TRI RAs and repeat-TRI RAs. Intimal tears were observed in 49 RAs (67.1%) and were more frequent in the distal than in the proximal RA (P = 0.001). Medial dissections were not uncommon (26 RAs, 35.6%). The frequency of acute injury was significantly higher in repeat-TRI RAs (P < 0.001). Intima/medial area, the maximum intimal thickness/medial thickness ratio, and per cent narrowing were all significantly greater in repeat-TRI RAs in the distal and proximal RA. Multivariate analysis revealed that a repeated TRI procedure was the only independent predictor of intimal thickening. CONCLUSION: Optical coherence tomography clearly demonstrated significant acute injuries and chronic intimal thickening of RA after TRI. Further study should evaluate the impact of these effects when TRI RAs are subsequently used as conduits, on long-term graft patency and on clinical outcomes after bypass surgery.

PECAM-1 is necessary for flow-induced vascular remodeling.

OBJECTIVE: Vascular remodeling is a physiological process that occurs in response to long-term changes in hemodynamic conditions, but may also contribute to the pathophysiology of intima-media thickening (IMT) and vascular disease. Shear stress detection by the endothelium is thought to be an important determinant of vascular remodeling. Previous work showed that platelet endothelial cell adhesion molecule-1 (PECAM-1) is a component of a mechanosensory complex that mediates endothelial cell (EC) responses to shear stress. METHODS AND RESULTS: We tested the hypothesis that PECAM-1 contributes to vascular remodeling by analyzing the response to partial carotid artery ligation in PECAM-1 knockout mice and wild-type littermates. PECAM-1 deficiency resulted in impaired vascular remodeling and significantly reduced IMT in areas of low flow. Inward remodeling was associated with PECAM-1-dependent NFkappaB activation, surface adhesion molecule expression, and leukocyte infiltration as well as Akt activation and vascular cell proliferation. CONCLUSIONS: PECAM-1 plays a crucial role in the activation of the NFkappaB and Akt pathways and inflammatory cell accumulation during vascular remodeling and IMT. Elucidation of some of the signals that drive vascular remodeling represent pharmacologically tractable targets for the treatment of restenosis after balloon angioplasty or stent placement.

The impact of different concentrations of sodium tetradecyl sulphate and initial balloon denudation on endothelial cell loss and tunica media injury in a model of foam sclerotherapy.

INTRODUCTION: Recanalisation rates (20-32%) 1-3 years after truncal vein foam sclerotherapy (FS) suggest thrombotic occlusion rather than irreversible vein wall injury. This study examines the injury inflicted by sodium tetradecyl sulphate (STD) foam before and after balloon endothelial denudation (BD). METHODS: In 20 patients undergoing great saphenous vein (GSV) stripping 1.5 cm proximal GSV were harvested (controls). The next 1.5 cm were harvested after in situ BD (n = 10) or no denudation (n = 10). These test segments were filled with 1% or 3% STD foam (5 min), flushed and fixed in formalin. Percentage endothelial cell loss (ECL) and tunica media injury were determined (H&E staining) and collagen structure assessed (transmission electron microscopy, TEM). RESULTS: Controls showed no injury. 1% and 3% STD foam caused 86.3% and 92.2% ECL (p < 0.001 versus controls; 1% versus 3%, p = 0.55). Endothelial cells persisted in all sections. BD increased ECL (1%: 96.9%, 3%: 98.1%, p = 0.01) Tunica media injury (smooth muscle vacuolation) was minimal (8.9% (1% STD) and 12% (3% STD) of its depth) and not enhanced by BD (1%: 8.7%, p = 0.93; 3%: 11.3%; p = 0.86). No collagen disruption occurred (TEM). CONCLUSIONS: Balloon denudation increased ECL but did not facilitate tunica media injury. Equivalent injury was inflicted by 1% and 3% STD.

Histopathological comparison of vascular wall damage created by external cross-clamp and endoluminal balloon occlusion techniques.

AIM: Almost all cross-clamps utilized in vascular surgery, even atraumatic clamps, have been shown to cause mechanical damage to the vascular wall. In recent years, surgical procedures using an endoluminal balloon technique have been reported as an alternative occlusion strategy. This study discusses the histopathological characteristics and comparison between vascular wall damage secondary to the two occlusion techniques in the early postoperative period. METHODS: Twelve adult rabbits were divided into two experimental groups: the clamp group (N. = 6) and the balloon group (N. = 6). External cross-clamp occlusion was applied to the abdominal aorta for 30 minutes via laparotomy in the clamp group. In the balloon group, occlusion was applied for 30 minutes by inflating the catheter balloon, which was inserted through the iliac artery and advanced into the abdominal aorta. The appropriate aortic segments were subsequently extracted in both groups and tissue samples were examined by light and electron microscopy. Finally, the samples were scored for grade of tissue damage. RESULTS: In both experimental groups, tissue damage was apparent. In the investigations carried out under light microscopy, it was observed that the damage caused by balloon occlusion was remarkably less than the damage caused by the cross-clamp technique. In the balloon group, eight tissue samples (66.7%) had grade 1 damage. On the other hand, five tissue samples had grade 3 damage, all of which were in the clamp group. Investigation by electron microscopy revealed that greater intimal, medial, and adventitial damage occurred in the vascular walls of the clamp group samples, and this also corresponded with an increase in immune response and intraluminal thrombosis. CONCLUSION: External clamp and internal balloon occlusion techniques applied to the aorta were compared, and widespread intimal and medial damage were observed in both techniques. However, endoluminal occlusion of the aorta should be the technique of choice in properly selected cases, since it results in lower damage grades, and it should also be used if application of an external clamp is technically difficult.

Delayed stenosis as a consequence of angioplasty for subarachnoid hemorrhage-induced vasospasm. Case report.

The authors report a case of restenosis in the bilateral internal carotid arteries (ICAs) following angioplasty for cerebral vasospasm. This 53-year-old woman suffering subarachnoid hemorrhage due to a ruptured posterior communicating artery aneurysm had severe vasospasm and underwent angioplasty of the left and right ICAs and middle cerebral arteries. Two months later, a follow-up CT angiogram revealed bilateral ICA stenoses. Transluminal angioplasty leads to long-term connective tissue damage in the medial and adventitial layers from the disruption of the arrangement of collagen fibers due to stretching and tearing, resulting in loss of transmission of contractile forces. Furthermore, following endothelial cell denudation and stretching and rupture of internal elastic lamina from angioplasty, reendothelialization of the intimal layer composed of smooth muscle cells may also explain the contractile properties of restenosis. Other factors such as macrophage-induced inflammation and reactive oxygen species accumulation may also contribute to restenosis. This is the second reported case of restenosis following angioplasty to treat vasospasm, although restenosis is a known complication of angioplasty for treatment of atherosclerosis. In addition, this is the first case of restenosis in the bilateral ICAs following angioplasty for vasospasm. This report presents an illustrative case study and reviews the pathophysiology of angioplasty and restenosis.

Stem cell renewal and contraction of the tunica media caused by a damaged blood vessel following a thick needle stab.

A marked difference in the healing process of the inferior vena cava in rats following a stab with a 17-G (1.48 mm phi) ultrahard zirconium ceramic (Zr) needle and with a common stainless steel (St) needle (also 1.48 mm phi was observed. This was investigated in vivo by histological imaging and biochemical micro-autoradiographic imaging using [2-(14)C]-thymidine as a biomarker in vivo. On the first day after the stab with either, the Zr or the St injection needle, the tunica adventitia showed the most pronounced damage, as evidenced by a large puncture wound characterized by blood congestion, but with few inflammatory cells being observed. A marked contraction of the tunica media was observed. The depth of the injury reached the tunica layer, but amounted to less than 1/3 of the needle diameter. Loose fragments of the endothelial lining were detected, together with scattered red corpuscles. The survival rate of the experimental animals amounted to less than 40% on the 3rd day after the stab by either the Zr or St needle, due to the large needle diameter. In addition, histological imaging of the wound area in the endothelial layer and tunica media showed considerable congestion and inflammation, which limited the evaluation of the regeneration status of the inferior vena cava of the surviving animals. Results were obtained from a few animals that displayed satisfactory recovery status. On the 3rd day after the stab by either the Zr or St injection needle, a relatively large proportion of the hemostatic clots became incorporated into the collagenous tissue, i.e. the tunica adventitia. A marked contraction of the tunica media was also observed, similar to that on the 1st day, following the needle injury. In the case of the endothelium (tunica intima), the injury caused by the Zr needle was reinfiltrated by adult stem cells 3 days after the stab, but the tunica media, composed of endothelial cells, still contained relatively contracted collagenous material. In addition, several interesting cell colonies were observed in the medial layer at the short distance from the boundary of the damaged tissue. It was assumed that these colonies produced medial tissue composed of collagenous supporting tissue or smooth muscle cells. In the experiment using the St needle, the incorporation of [2-(14)C]-thymidine into the nucleus of the stem cells was observed in the small capillaries of the tunica media, but not in the support cells of the latter.

Mechanisms of late lumen loss after antiproliferative percutaneous coronary intervention using beta-irradiation in a porcine model of restenosis.

BACKGROUND: The short-term results for the prevention of coronary restenosis after intravascular brachytherapy (IVBT) and use of drug-eluting stents (DESs) are excellent. The long-term results either lack or present with late complications (e.g., late thrombosis and late catch-up phenomenon leading to late restenosis even years after the initial procedure). Both IVBT and DESs mediate their potent antirestenotic effects via a cytostatic mechanism, but the cardiovascular pathology at late time points after the use of these antiproliferative therapies is incompletely understood. This study investigated the long-term effects of antiproliferative beta-irradiation in a clinically relevant porcine coronary model to address the pathophysiology of late coronary restenosis after antiproliferative vascular interventions. METHODS: We performed percutaneous transluminal coronary angioplasty (PTCA) in two major coronary arteries in 12 domestic crossbred pigs. One of the two balloon-injured segments was randomly assigned to receive immediate beta-irradiation (PTCA+IVBT group) using a noncentered delivery catheter (20 Gy; Novoste Beta-Cath System, Novoste, Norcross, GA, USA). The animals were sacrificed after 14 days (n=6) or 3 months (n=6). RESULTS: The luminal area in the PTCA+IVBT group decreased significantly 3 months after the intervention as compared with that in the PTCA group (PTCA 3.45+/-0.46 mm2 vs. PTCA+IVBT 1.22+/-0.26 mm2; P=.0017). This lumen loss was primarily due to shrinkage of the external elastic lamina area (negative arterial remodeling; PTCA 5.22+/-0.27 mm2 vs. PTCA+IVBT 3.42+/-0.45 mm2; P=.0064), which was accompanied by an increase in the adventitial area (PTCA 3.07+/-0.2 mm2 vs. PTCA+IVBT 5.41+/-0.5 mm2; P=.0049). CONCLUSIONS: The application of antiproliferative radiation in a porcine coronary model caused an early beneficial effect (reduction of intimal-medial lesion and luminal gain) that was followed by a late lumen loss primarily due to negative arterial remodeling. This mechanism may in part help us understand the pathophysiology of late adverse events occurring after IVBT.

Effects of percutaneous transluminal angioplasty and endovascular brachytherapy on vascular remodeling of human femoropopliteal artery by noninvasive magnetic resonance imaging.

BACKGROUND: Percutaneous transluminal angioplasty (PTA) of severely stenotic peripheral vascular lesions is hampered by a higher restenosis rate. The effects of PTA on vascular wall as well as the effects of the antirestenotic properties of endovascular brachytherapy (EVBT) remain unclear. MRI allows in vivo noninvasive assessment of the vascular effects of such treatment strategies. We sought to elucidate the vascular effect of PTA and PTA+EVBT by serial MRI. METHODS AND RESULTS: Twenty symptomatic patients with severe stenosis of the femoropopliteal artery were randomly assigned to PTA (n=10) or PTA+EVBT (n=10; 14 Gy by gamma-irradiation source) and imaged by high-resolution MRI before and 24 hours and 3 months after intervention. An independent observer blinded to the procedure analyzed the MRI data. At 24 hours, cross-sectional MRI revealed that lumen area (86% and 67%) and total vessel area (47% and 34%) increased similarly in the PTA and PTA+EVBT groups, respectively. All patients showed severe splitting of the atherosclerotic plaque, resulting in an irregularly shaped lumen. At 3 months, MRI revealed a significant difference in lumen area change between the PTA and PTA+EVBT groups (40% and 106%, respectively; P=0.026) and in the total vessel area (14% and 39%, respectively; P=0.018). At 3 months, plaque disruption was still present in 50% of the patients treated with PTA+EVBT. CONCLUSIONS: After PTA, there is deep disruption of the atherosclerotic plaques and an extensive remodeling process of the arterial wall. Luminal loss after PTA is partially due to inward vessel remodeling. Brachytherapy prevents inward remodeling and induces an increase in lumen area but partially prevents healing of disrupted vessel surface.

Relation of deep arterial resection and coronary artery aneurysms after directional coronary atherectomy.

OBJECTIVES: The aims of this study were to document the frequency of coronary artery aneurysm formation in patients undergoing directional coronary atherectomy and to determine the relation of such aneurysms to the depth of arterial resection. BACKGROUND: Deep arterial injury is relatively frequent with the use of directional coronary atherectomy, but the potential for subsequent coronary artery aneurysm formation is unknown. METHODS: Results in a consecutive series of 64 successfully treated patients (a total of 69 lesions; mean angiographic follow-up at 5 months) treated with directional coronary atherectomy were retrospectively analyzed with use of quantitative angiographic and histologic data. RESULTS: Coronary aneurysms (ratio of dilated vessel segment to the adjacent reference segment > 1.2:1) occurred in seven patients (10%). The only significant clinical correlate of aneurysm formation was a relatively shorter duration of angina. There were no significant preprocedural angiographic predictors of aneurysms, although 6 (86%) of the 7 aneurysmal lesions arose from restenosis lesions compared with 30 (48%) of 62 lesions with no subsequent aneurysm development (p = 0.06). Histopathologic examination of 414 specimens from 68 treated lesions showed no significant difference in the occurrence of subintimal resection (media +/- adventitia) between those with and without subsequent aneurysm (29% vs. 22%). Media alone was found in 14% of specimens from lesions that later became aneurysmal versus 15% of those that did not; adventitial resection was found in 14% and 7% of specimens, respectively (p = 0.08), with relatively more adventitia per specimen from those with aneurysm (55% vs. 30% without aneurysm, p = 0.08). CONCLUSIONS: Aneurysms occur relatively frequently after directional coronary atherectomy. Although there was no statistically significant correlation with the depth of arterial resection, the evidence from this study suggests that the role of adventitial resection in the occurrence of late aneurysm development should be explored further.

Increased intimal apoptosis in coronary atherosclerotic vessel segments lacking compensatory enlargement.

OBJECTIVES: In a histopathologic study, we assessed the balance of cell proliferation and apoptosis by counting the number of apoptotic and proliferating cell nuclear antigen-positive cells in freshly harvested atherectomy specimens from 34 patients. BACKGROUND: Remodeling of human coronary arteries is an adaptive process that alters vascular lumen size. METHODS: Intravascular ultrasound was performed prior to atherectomy. Total vessel area (area within the external elastic lamina [EEL]), lumen area and plaque area were measured at the region of interest (ROI), and at a proximal and distal reference segment, utilizing the formula Delta(%)=100x(ROI-reference segment)/reference segment. Positive arterial remodeling (R+) resulting in luminal expansion was defined as DeltaEEL >10%. Absence of remodeling (0 < DeltaEEL <10%) and constrictive arterial remodeling (DeltaEEL <0) were considered as neutral remodeling (R0) and negative remodeling (R-), respectively. RESULTS: In R- lesions, apoptotic indices (APO) were significantly elevated (17.17 +/- 2.19%) compared with R+ lesions (4.89 +/- 1.7%; p = 0.0007). In a rabbit iliac percutaneous transluminal coronary angioplasty model intimal apoptosis was increased four weeks after balloon angioplasty injury (APO 8.8 +/- 0.03%) compared with contralateral untreated segments (APO 3.0 +/- 0.04%, n = 6). Lesions with an EEL/intimal area <3.0 showed significantly more intimal apoptosis than untreated lesions (p = 0.02). CONCLUSIONS: The data indicate that constrictive remodeling of atherosclerotic coronary lesions is associated with increased apoptosis of intimal cells. We speculate that increased apoptosis is due to extensive plaque healing after episodes of symptomatic or asymptomatic plaque rupture.

Eosinophilic Coronary Periarteritis with Arterial Dissection: The Mast Cell Hypothesis.

A subset of coronary arterial dissections is associated with eosinophilic coronary periarteritis (ECPA); however, the pathogenesis of the process remains unclear. Mast cells normally reside in coronary arterial adventitia and are known mediators of eosinophilic inflammatory conditions such as type I hypersensitivity reactions. We report two cases in which coronary arterial dissection with ECPA was detected at autopsy. Tryptase, CD68, CD4, CD8, and CD1a immunohistochemical staining was performed to better characterize inflammation. While eosinophils represented a prominent periadventitial inflammatory cell, there were slightly more lymphocytes: CD4/CD8 ratios were within expected reference ranges. There were moderate numbers of macrophages, and few neutrophils or dendritic cells. Numbers of mast cells in dissected versus nondissected sections were compared: adventitial mast cell densities were threefold higher in dissected portions and showed a trend toward increased degranulation. These findings suggest that mast cells may play a role in orchestrating inflammation in cases of ECPA.