Periadventitial Tissue Research Articles

Abstract 243: Local Periadventitial Delivery Of Dexamethasone Improves Murine Deep Vein Thrombosis Resolution

Background: Post deep vein thrombosis (DVT), up to 30-50% of patients will develop post-thrombotic syndrome (PTS), despite anticoagulation. Currently no preventive therapies, including catheter-based thrombectomy/thrombolysis (CDT), have shown to reduce PTS. Local steroid therapy adjunct to CDT is being tested clinically for DVT patients in the DEXTERITY trials, but minimal mechanistic data exists on DVT resolution. Here, we investigate effects of local dexamethasone (DEX) therapy on murine DVT resolution. Method: C57/BL6 male mice (n=146) underwent inferior vena cava (IVC) complete ligation to develop stasis DVT on day 0 (D0) followed by mechanical de-ligation on D2 to spur restoration of blood flow (RBF). On D2, mice were injected with PBS/DEX (0.1, 0.2, or 0.5 mg/mouse, 60μl volume, across four zones) in the periadventitial tissue of thrombosed IVC, with or without de-ligation (Fig. A-B). Mice underwent D4&D8 serial ultrasound imaging of IVC blood flow to assess RBF-defined as IVC mean flow velocity > 0 mL/sec. D8 thrombus burden was measured followed by histological/picrosirius red assessment of vein wall fibrosis. Results: N=6-11 mice per group underwent IVC DVT creation. Low-dose (0.1 mg) but not higher doses of DEX reduced thrombus burden (p=0.02) and weight (p=0.01) on D8 (Fig. C-D). Low-dose DEX increased D4 RBF rates and mean flow velocity (MFV) (Fig. E-F). Complete IVC stasis without de-ligation but with DEX non-significantly reduced thrombus burden and weight (Fig. G-H). Low-dose DEX further decreased vein wall fibrosis (Fig. I; p=0.001). D8 thrombi exhibited reduced macrophage content with DEX (Fig. J; n=15-18 sections/group, p=0.007). Conclusion: Following stasis DVT induction, locally delivered low-dose DEX improves DVT resolution by reducing thrombus burden, vein wall injury, macrophage content, and increases RBF rate. These data provide a scientific foundation for ongoing DEXTERITY trail testing adjunct DEX for DVT patients undergoing CDT.

Abstract 15176: Development of Femoral Artery Denervation Models for Vascular Remodeling

Introduction: Restenosis is a common cause of vascular device failure. An important contributor is the transdifferentiation of vascular smooth muscle cells (VSMCs) from a contractile to synthetic phenotype. Healthy arteries are innervated by sympathetic nerves to regulate VSMC contractility and phenotype, yet this interaction has been overlooked in pathological vascular remodeling such as restenosis. Hypothesis: Sympathetic denervation of the femoral artery will lead to transdifferentiation of arterial VSMC and pathological remodeling of the arterial structure. Methods: The femoral arteries of male BALB/c mice were surgically exposed and treated with specific dopaminergic neurotoxin 6-hydroxydopamine (6-OHDA) or vehicle for 5 minutes. In the model of long-term denervation, the mice were subcutaneously injected with 6-OHDA or vehicle weekly for 4 weeks. Femoral arteries and peri-adventitial tissue were harvested for histology. Innervation density was calculated as the number of sympathetic nerve fibers (tyrosine hydroxylase-positive) normalized to the medial layer area (α-smooth muscle actin-positive). Extracellular matrix (ECM) composition was visualized with Masson’s trichrome and Verhoeff's elastic staining. Results: One week after surgery, 6-OHDA-treated arteries had a notable reduction in sympathetic nerve density compared to controls (2.9 vs. 11.7 fibers/10,000 μm 2 [P=.22, n=2]). This difference decreased at 2 weeks (6.8 vs. 8.0 fibers/10,000 μm 2 [P=0.50, n=3]) and at 4 weeks (4.4 vs. 5.0 fibers/10,000 μm 2 [P=0.83, n=3]), suggesting nerve recovery. No difference was observed in ECM composition. Tissues harvested at 1 and 4 weeks in the 6-OHDA injection model demonstrate qualitative denervation of the treated limb compared to control. Conclusions: Sympathetic denervation of murine femoral arteries can be achieved by direct surgical application or subcutaneous injection of 6-OHDA. Future work will characterize vascular remodeling after long-term denervation and combine denervation with vascular injury. If a causal relationship can be identified between sympathetic denervation and VSMC pathology, engineering reinnervation could be a viable approach for future graft design.

Aspirin treatment prevents inflammation in experimental bifurcation aneurysms in New Zealand White rabbits

BackgroundAneurysm wall degeneration is linked to growth and rupture. To address the effect of aspirin (ASA) on aneurysm formation under various wall conditions, this issue was analyzed in a novel...

Contemporary management of carotid body tumors in a Midwestern academic center

BackgroundCarotid body tumors are rare, neurogenic tumors arising from the periadventitial chemoreceptive tissue of the carotid body. The purpose of this study is to ascertain the presentation and preoperative risk factors associated with surgical resection. MethodsA single-center retrospective review of 25 carotid body tumor resections from 2002 to 2019. Demographics, periprocedural details, and postoperative outcomes were analyzed using Stata (Stata Corporation, College Station, TX). ResultsAmong 25 patients, 64% were women, 84% were asymptomatic, and the mean age was 49 years (range 21–79). Forty-four percent of tumors were Shamblin III. Nine patients underwent preoperative embolization but did not correlate with decreased blood loss (299 cm3 vs 205 cm3, P = .35). The 30-day death, stroke, and cranial nerve injury rates were 0%, 8%, and 32%, respectively. Cranial nerve injuries included 20% vagus, 4% hypoglossal, 4% facial, and 4% glossopharyngeal, with permanent deficits in 4% (n = 1). Mean length of stay was 3.0 days (range 1–9 days). At a mean follow-up of 12 months (range 1–63 months), there has been no recurrence. ConclusionAlthough carotid body tumors are uncommon in the Midwest, complete surgical resection is curative of these typically hormonally inactive tumors. Preoperative embolization did not affect blood loss, and the incidence of death, stroke, and permanent cranial nerve injury rates remained very low.

Significance of inflammation restricted to adventitial/periadventitial tissue on temporal artery biopsy

ObjectiveTo evaluate the characteristics and significance of inflammation restricted (RI) to the adventitial and/or periadventitial tissue on temporal artery biopsy (TAB). MethodsWe studied a retrospective cohort of 80 patients with RI, extending our earlier series of 39 patients. For comparison purposes, we collected the same data from 254 patients with transmural inflammation (TMI) and 81 TAB-negative patients. A review of the literature was also performed. ResultsA final diagnosis of giant cells arteritis (GCA) and/or polymyalgia rheumatica (PMR) was observed in 86% of patients with RI. Compared to TMI, GCA diagnosis was significantly less frequently observed in patients with RI and in those TAB-negative (p < 0.0001), while cranial manifestations were significantly less frequent (p = 0.001) and ESR and CRP values at diagnosis significantly reduced (p < 0.0001). PMR, permanent visual loss, and large vessel involvement at diagnosis were equally present in the 3 subgroups. The median duration of prednisone therapy, the cumulative prednisone dosages, and the relapse and long-term remission rates were similar between patients with GCA-RI and those with TMI. The positive likelihood ratios (LRs) of pathological evidence of RI at TAB for GCA or GCA/PMR diagnoses were 0.88 (CI, 0.61–1.27) and 1.15 (CI, 0.67–1.99), while that of inflammation limited to adventitia was 1.37 (CI, 0.59–3.19) and 3.77 (CI, 0.53–26.72). In the literature review, the positive LR of RI for GCA diagnosis was 0.92 (CI, 0.68–1.25). ConclusionA large part of the patients with RI have GCA/PMR, however, the diagnostic value of RI for GCA diagnosis is not relevant.

Resident Perspectives

Resident Perspectives

Periadventitial tissue examination in temporal artery biopsies for suspected giant cell arteritis: a case series and literature review

Giant cell arteritis (GCA) is a systemic vasculitis, affecting medium- and large-sized vessels. Temporal artery biopsies (TABs) are currently the benchmark for diagnosing suspected cases of GCA. Often, the temporal artery is "skeletonized," and surrounding soft tissue is discarded at the time of biopsy. The purpose of this study was to identify cases in which diagnoses were made through examination of periadventitial soft tissue in nonskeletonized TABs. Retrospective observational case series and literature review. Six patients were recruited on a case-by-case basis. bilateral TABs for suspected GCA and periadventitial findings leading to appropriate diagnosis. none. A retrospective chart review was performed to collect patient demographics and clinical information in 2 academic institutions in Ontario, Canada. The primary outcome measure was identification of histopathological diagnoses made through examination of periadventitial soft tissue in TABs performed for suspected GCA. Two patients were diagnosed with GCA, one of which had a concurrent diagnosis of chronic lymphocytic leukemia. Four patients were diagnosed with small vessel vasculitis, 3 of which were antineutrophil cytoplasmic antibody-related vasculitides. All patients had evidence of a disease limited to the periadventitial tissue of the TAB. The results are limited by the study's size. This case series demonstrates that other serious conditions may declare themselves with symptoms similar to that of GCA. We recommend that surgeons perform a nonskeletonized TAB in all cases of suspected GCA and that pathologists adequately examine the periadventitial tissue in these biopsies to ensure appropriate diagnosis.

Morphological evaluation of sympathetic renal innervation in patients with autosomal dominant polycystic kidney disease.

Several evidences support the hypothesis that patients affected by autosomal dominant polycystic kidney disease (ASPKD) show a sympathetic renal hyperactivity. Nevertheless, no morphological evidences are available yet. Therefore, the aim of the study was to demonstrate that an increase in sympathetic renal artery innervation was present in the ADPKD patients by using histological methods. In addition, here we correlated the sympathetic renal artery innervation with the evolutionary state of ADPKD (increase in volume of kidney, onset of chronic renal failure and hypertension). To this end, peri-adventitial innervation of renal arteries was studied using morphological methods from 49 patients in total: 29 underwent surgical nephrectomies for ADPKD and 20 non-dialysis patients (CTRL group) undergoing nephrectomy for other diseases. Nerve density (number of nerves per mm2) was evaluated in the peri-adventitial tissue in a concentric ring that was located within 2mm from the beginning of the adventitia by using immunohistochemistry. The total nerve density was significantly increased in the ADPKD group (1.26 ± 0.82 × mm2) as compared to controls (0.78 ± 0.40 × mm2) (p = 0.02). Hypertensive patients with ADPKD showed a greater nerve density than control hypertensives. However, the increase in renal sympathetic innervation in the ADPKD patients was found to be independent of hypertension, resistance to antihypertensive therapy, age, sex and kidney volume, as demonstrated by the uni and multivariate analysis. In conclusion, our study better clarifies the effect of sympathetic hyperactivity in the progression of polycystic disease.

Intravascular imaging, histopathological analysis, and catecholamine quantification following catheter-based renal denervation in a swine model: the impact of prebifurcation energy delivery.

The purpose of this study was to evaluate the impact of prebifurcation renal denervation in a swine model and assess its safety through optical coherence tomography (OCT). Prebifurcation renal denervation with a multi-electrode catheter was performed in one renal artery of 12 healthy pigs, with the contralateral artery and kidney being used as controls. Angiograms and OCT pullbacks were obtained peri-procedurally and 1 month post procedure. Renal tissue catecholamines were quantified, and the arterial wall and peri-adventitial tissue were analyzed histologically. Intraluminal changes (endothelial swelling, spasm, and thrombus formation) were observed acutely by OCT in most of the treated arteries and were no longer visible at follow-up. Histology revealed a statistically significant accumulation of collagen (fibrosis) and a near absence of tyrosine hydroxylase labeling in the denervated artery, suggesting a clear reduction in nervous terminals. Renal tissue catecholamine levels were similar between both sides, probably due to the low number of ablation points and the renorenal reflex. The present study demonstrates that renal denervation is associated with acute intimal disruptions, areas of fibrosis, and a reduction in nervous terminals. The lack of difference in renal tissue catecholamine levels is indicative of the need to perform the highest and safest number of ablation points in both renal arteries. These findings are important because they demonstrate the histological consequences of radiofrequency energy application and its medium-term safety.

Immunophenotypic analysis of the chronological events of tissue repair in aortic medial dissections.

Acute medial dissection of aorta can occur in the context of a sudden and unexpected death. For medico-legal reasons it is important to estimate as accurately the histological age of dissections. We evaluated the additional value of a systematic application of immunohistochemistry, compared with conventional histology only, in determining chronological steps of injury and repair. Thirty two paraffin embedded specimens of aortic dissection were retrospectively allocated to one of four defined stages: acute (I), subacute (II), early organizing (III) and scarring (IV) using Hematoxylin and Eosin and Elastica van Gieson stained sections. Subsequent immunohistochemically staining was performed with the following markers: (myeloperoxidase (neutrophils), citrullinated-Histone 3 (neutrophil extracellular traps), CD68 (macrophages), CD3 (T-cells), CD31 and CD34 (endothelial cells), and smooth muscle actin. Immune stained sections were scored semi-quantitatively. Histologically, five cases were identified as stage I, 16 as II, 7 as III and 4 as IV. Additional immunostaining for smooth muscle cells and endothelial cells altered the classification in 25% of cases (all in groups II and III). Immunostaining and semi-quantitative grading of involvement of neutrophils, macrophages and NETs also provided specific distribution patterns over the 4 age categories, including unexpected involvement of the peri adventitial fat tissue. In conclusion, it appears that semi-quantitative immunohistochemistry of resident vascular wall cells, inflammatory cells and NETS represents a useful adjunct in detailed histopathological grading of the chronological age of aortic dissections.

Retraction note: A histopathological analysis of the epidemiology of coronary atherosclerosis: an autopsy study.

Atherosclerosis accounts for a large proportion of cardiovascular system associated morbidity and mortality. We studied the possible association between the histopathological changes of the coronary atherosclerotic lesions and the risk of sudden cardiac death (SCD) using autopsy cases. We performed an autopsy analysis (n = 13, 4 women, 9 men mean age 67.5 years; age range 56–93 years) of SCD which occurred in patients aged over 50 years during March 2010 to December 2013. The following variables were considered: sex, age, medical history, autopsy findings to macroscopic and histological evaluation of the heart. The autopsies were performed according to standard techniques. In all subjects, the heart was dissected following standard autopsy protocol and a 5 cm section of the right coronary artery (RCA) in the atrio-ventricular groove from its origin, a 5 cm segment of the left anterior descending artery (LADA) distal to the origin of the circumflex artery, but including the region of origin of the circumflex branch and left coronary artery (LCA) from its origin till the circumflex branch were excised, dissected out, fixed in 10 % formalin, marked for identification and sent for histopathological analysis. Atherosclerotic plaques were identified in 6.5 % of specimens, 69.34 % of males and 30.66 % of female. Such plaques were typically concentric and more represented with necrosis, calcification, cholesterol crystals, and giant cells, as well as had a higher inflammatory cell count. Furthermore, intima and media thickness of coronary arteries were significantly higher in studied specimens with visualize the connective tissue layers of the adventitia and the fatty acid containing adipose cells in the periadventitial tissue. Furthermore, the degree of microscopic lesion of atherosclerosis increased proportionally with the increase in the intensity of lipid deposition and with the percentage of collagen in the atherosclerotic plaques. In this study, age estimate to be a risk factor for coronary atherosclerosis in individuals more than 50 years old and may be used to predict SCD. Altogether, an enhanced understanding of the pathobiologic processes responsible for atherosclerotic changes might allow for early identification of a high-risk coronary plaque and thereby provide a rationale for innovative diagnostic and/or therapeutic strategies for the management of coronary patients and prevention of acute coronary syndromes.

English

We performed an autopsy analysis (N=16, 5women, 11 Men Of SCD which occurred in patients aged over 50 years during 2011 To 2014. The following variables were considered: Sex, Age, Medical History, Autopsy findings to macroscopic and histological evaluation of the Heart. The autopsies were performed according to standard techniques. In all subjects, the heart was dissected following standard autopsy protocol and a 5 cm section of the right Coronary Artery (RCA) in the Atrio-Ventricular Groove from its origin, A 5 cm segment of the Left Anterior Descending Artery (LADA) distal to the origin of the Circumflex Artery, but including the region of origin of the circumflex branch and Left Coronary Artery (LCA) from its origin till the Circumflex Branch were excised, Dissected Out, Fixed In 10 % Formalin, Marked For Identification And Sent For Histopathological Analysis. Atherosclerotic Plaques Were Identified In 6.5 % Of Specimens, 69 % Of Males And 31 % Of Female. Such Plaques Were Typically Concentric And More Represented With Necrosis, Calcification, Cholesterol Crystals, And Giant Cells, As Well As Had A Higher Inflammatory Cell Count. Furthermore, Intima And Media Thickness Of Coronary Arteries Were Significantly Higher In Studied Specimens With Visualize The Connective Tissue Layers Of The Adventitia And The Fatty Acid Containing Adipose Cells In The Periadventitial Tissue. In This Study, Age Estimate To Be A Risk Factor For Coronary Atherosclerosis In Individuals More Than 50 Years Old And May Be Used To Predict SCD. Altogether, An Enhanced Understanding Of The Pathobiologic Processes Responsible For Atherosclerotic Changes Might Allow For Early Identification Of A High-Risk Coronary Plaque And There By Provide A Rationale For Innovative Diagnostic And/Or Therapeutic Strategies For The Management Of Coronary Patients And

A histopathological analysis of the epidemiology of coronary atherosclerosis: an autopsy study.

BackgroundAtherosclerosis accounts for a large proportion of cardiovascular system associated morbidity and mortality. We studied the possible association between the histopathological changes of the coronary atherosclerotic lesions and the risk of sudden cardiac death (SCD) using autopsy cases.MethodsWe performed an autopsy analysis (n = 13, 4 women, 9 men mean age 67.5 years; age range 56–93 years) of SCD which occurred in patients aged over 50 years during March 2010 to December 2013. The following variables were considered: sex, age, medical history, autopsy findings to macroscopic and histological evaluation of the heart. The autopsies were performed according to standard techniques. In all subjects, the heart was dissected following standard autopsy protocol and a 5 cm section of the right coronary artery (RCA) in the atrio-ventricular groove from its origin, a 5 cm segment of the left anterior descending artery (LADA) distal to the origin of the circumflex artery, but including the region of origin of the circumflex branch and left coronary artery (LCA) from its origin till the circumflex branch were excised, dissected out, fixed in 10 % formalin, marked for identification and sent for histopathological analysis.ResultsAtherosclerotic plaques were identified in 6.5 % of specimens, 69.34 % of males and 30.66 % of female. Such plaques were typically concentric and more represented with necrosis, calcification, cholesterol crystals, and giant cells, as well as had a higher inflammatory cell count. Furthermore, intima and media thickness of coronary arteries were significantly higher in studied specimens with visualize the connective tissue layers of the adventitia and the fatty acid containing adipose cells in the periadventitial tissue. Furthermore, the degree of microscopic lesion of atherosclerosis increased proportionally with the increase in the intensity of lipid deposition and with the percentage of collagen in the atherosclerotic plaques.ConclusionIn this study, age estimate to be a risk factor for coronary atherosclerosis in individuals more than 50 years old and may be used to predict SCD. Altogether, an enhanced understanding of the pathobiologic processes responsible for atherosclerotic changes might allow for early identification of a high-risk coronary plaque and thereby provide a rationale for innovative diagnostic and/or therapeutic strategies for the management of coronary patients and prevention of acute coronary syndromes.

Thoracic aortic rupture and aortopulmonary fistulation in the Friesian horse: histomorphologic characterization.

Aortic rupture in horses is a rare condition. Although it is relatively common in the Friesian breed, only limited histopathologic information is available. Twenty Friesian horses (1-10 years old) were diagnosed with aortic rupture by postmortem examination. Ruptured aortic walls were analyzed with histology and immunohistochemistry. Based on the histologic and immunohistochemical findings, these cases were divided into 3 groups: acute (n = 4, 20%), subacute (n = 8, 40%), and chronic (n = 8, 40%). Features common to samples from horses in all groups included accumulation of mucoid material; disorganization and fragmentation of the elastic laminae; aortic medial smooth muscle hypertrophy; and medial necrosis of varying degrees, ranging from mild and patchy in the acute cases to severe midzonal necrosis in the chronic cases. Inflammation, most likely secondary to medial necrosis, varied from predominantly neutrophilic infiltrates in the media and periadventitial tissue in the acute group to the presence of mainly hemosiderophages in the periadventitial tissue in the chronic group. Medial fibrosis with aberrant collagen morphology was seen in the subacute group and, more commonly, in the chronic group. Only minimal changes were seen in the aortic vasa vasorum. Smooth muscle hypertrophy and accumulation of mucoid material were not related to the age of the lesions. The findings of this study suggest that a connective tissue disorder affecting elastin or collagen in the aortic media is potentially the underlying cause of aortic rupture in Friesian horses.

Spectroscopic intravascular photoacoustic imaging of lipids in atherosclerosis

The natural history of atherosclerosis is marked by changes in the lipid biochemistry in the diseased arterial wall. As lesions become more vulnerable, different cholesterol species accumulate in the plaque. Understanding unstable atherosclerosis as a pharmacological and interventional therapeutic target requires chemically specific imaging of disease foci. In this study, we aim to image atherosclerotic plaque lipids and other vessel wall constituents with spectroscopic intravascular photoacoustics (sIVPA). sIVPA imaging can identify lipids in human coronary atherosclerotic plaque by relying on contrast in the near-infrared absorption spectra of the arterial wall components. Using reference spectra acquired on pure compounds, we analyzed sIVPA data from human coronary plaques ex vivo, to image plaque composition in terms of cholesterol and cholesterol ester content. In addition, we visualized the deeper lying connective tissue layers of the adventitia, as well as the fatty acid containing adipose cells in the peri-adventitial tissue. We performed simultaneous coregistered IVUS imaging to obtain complementary morphological information. Results were corroborated by histopathology. sIVPA imaging can distinguish the most prevalent lipid components of human atherosclerotic plaques and also visualize the connective tissue layers of the adventitia and the fatty acid containing adipose cells in the peri-adventitial tissue.

Lipid detection in atherosclerotic human coronaries by spectroscopic intravascular photoacoustic imaging

The presence of lipids in atherosclerotic coronary lesions is an important determinant of their potential to trigger acute coronary events. Spectroscopic intravascular photoacoustic imaging (sIVPA) has the potential to automatically detect lipids in atherosclerotic lesions. For real-time in vivo imaging, limiting the number of excitation wavelengths is crucial. We explored methods for plaque lipid detection using sIVPA, with the aim to minimize the number of laser pulses per image line. A combined intravascular ultrasound (IVUS) and photoacoustic imaging system was used to image a vessel phantom and human coronary arteries ex vivo. We acquired co-registered cross-sectional images at several wavelengths near 1200 nm, a lipid-specific absorption band. Correlating the photoacoustic spectra at 6 or 3 wavelengths from 1185 to 1235 nm with the absorption spectrum of cholesterol and peri-adventitial tissue, we could detect and differentiate the lipids in the atherosclerotic plaque and peri-adventitial lipids, respectively. With two wavelengths, both plaque and peri-adventitial lipids were detected but could not be distinguished.

External aortic root support: a histological and mechanical study in sheep†

Personalized external aortic root support has completed initial evaluation and has technology appraisal in the UK for patients with Marfan syndrome for use as an alternative to root replacement. Its long-term success in preventing aortic dissection remains uncertain. Here, we report a study in sheep to establish whether the externally supporting mesh, as used clinically, is biologically incorporated. The strength of the resulting mesh/artery composite has been tested. The carotid artery of growing sheep (n=6) was enclosed in a mesh sleeve made of a polymer, polyethylene terephthalate. After a predefined interval of 4-6 months, a length of the artery was excised, including the sleeved and unsleeved portions, and was stress tested and examined histologically. One animal died of pneumonia 7 days after implantation. Comparing sleeved with normal segments, the overall thickness was increased and there was a fibrotic sheet in the periarterial space. The overall vessel wall architecture was preserved in all specimens. Although media thickness of ensleeved arteries was smaller and in one animal mild oedema was found in one quadrant of the outer part of the media. There was a significant increase in stiffness and maximum tensile strength of the supported segments compared with normal arterial tissue. Polyethylene terephthalate mesh, as used for the external support of the dilated aortic root in Marfan syndrome, becomes incorporated in the periadventitial tissue of the carotid artery of sheep. Limited thinning of the media, without any signs of inflammation or medial necrosis, was visible. There was a significantly greater tensile strength in the carotid artery/mesh composite compared with the unsleeved carotid artery.

Eosinophilic coronary periarteritis presenting with vasospastic angina and sudden death: a new cause and manifestation of Kounis syndrome?

Dear Editor, In a very interesting report published in Virchows Archives [1], seven patients were described suffering from angina pectoris who died suddenly in the morning hours. Histological diagnosis revealed a new pathological entity, which was named eosinophilic coronary periarteritis. All of these patients had inflammatory infiltrates, mainly eosinophilic, in coronary adventitia and periadventitial soft tissue. One of them also had eosinophilic infiltration of the intima and another had infiltration of the medial smooth muscle layers by a small number of eosinophils. This report raises important issues concerning the causality and clinical presentation of hypersensitivity-associated acute coronary syndrome, also known as Kounis syndrome [2]. This is a hypersensitivity angina syndrome, which can progress to acute myocardial infarction and sudden death. It is a ubiquitous disease affecting patients of any age, with a continuously increasing list of causes, broadening clinical manifestations, and covering a wide spectrum of activation disorders of mast cells and other interrelated and interacting inflammatory cells. Platelets with FcγRI, FcγRII, FceRI, and FceRII receptors are also involved in the development of this syndrome. Kounis syndrome can complicate the Churg–Strauss syndrome, which is sometimes associated with coronary artery spasm with repeated angina pectorislike attacks and/or acute myocardial infarction [3]. Eosinophilic coronary arteritis can also complicate Churg–Strauss syndrome and can clinically present as type I and type II variants of Kounis syndrome [2]. Eosinophilic coronary periarteritis might be a further evolution of entities previously described as “isolated eosinophilic coronary arteritis,” “eosinophilic arteritis,” “eosinophilic coronary arteritis,” and “limited form of Churg–Strauss syndrome.” Indeed, the first description already more than six decades ago was named “diffuse eosinophilic arteritis” [4]. Although the authors of the above report [1] did not describe any presence of mast cells during histological examination, other reports emphasized eosinophilic infiltration of adventitia, media, and intimal subendothelium together with diffusely distributed mast cells [5]. This could be an important finding because eosinophilic receptors facilitate eosinophil chemotaxis toward mast cells that are the major producers of an array of inflammatory soluble mediators, including histamine, which can induce Kounis syndrome. Soluble mediators secreted by mast cells and eosinophils modulate reciprocal interactions between these two cells in the socalled “allergic effector unit.” Eosinophils are bone marrow-derived granulocytic leukocytes, which normally reside in tissues and express H4 histamine receptors. Eosinophils respond to histamine in changing cell shape and upregulation of adhesion molecules and chemotaxis, and these responses are mediated by the H4 receptor N. G. Kounis (*) Department of Medical Sciences, Patras Highest Institute of Education and Technology, Queen Olgas Square, 7 Aratou Street, Patras 26221, Greece e-mail: ngkounis@otenet.gr

Cardiac denervation procedure to treat refractory angina in a patient with Churg-Strauss syndrome and non-obstructive coronary lesions

Cardiac involvement in Churg-Strauss syndrome is common and represents the main cause of mortality. We report the case of a patient with Churg-Strauss vasculitis, mitral regurgitation with left ventricular dysfunction, paroxysmal atrial fibrillation and refractory angina with non-significant coronary lesions. Cardiac denervation was proposed as an associated procedure to treat angina. The total removal of peri-adventitial and adventitial tissue around the superior vena cava, ascending aorta and main pulmonary trunk was performed. After 3 months of follow-up, the patient was angina-free and could resume his normal lifestyle.

Thermal intravascular photoacoustic imaging

Intravascular photoacoustics (IVPA)—a minimally invasive imaging technique with contrast related to optical absorption properties of tissue, can be used to visualize atherosclerotic plaques. However, the amplitude of photoacoustic signals is also related to a temperature dependent, tissue specific parameter—the Grüneisen parameter. Therefore, photoacoustic signals measured at different temperatures may reveal information about tissue composition. In this study, thermal IVPA (tIVPA) imaging was introduced. The imaging studies were performed using an ex vivo atherosclerotic rabbit aorta. Temperature dependent photoacoustic responses from lipid in plaques and lipid in periadventitial tissue were different, thus allowing tIVPA images to delineate the location of lipid-rich plaques. The results indicate that tIVPA imaging has a potential to characterize tissue composition in atherosclerotic vessels.