Intimal Hypertrophy Research Articles

CLINICAL SIGNIFICANCE OF LINEAR SHADOWS INSIDE CORONARY ARTERIAL LESIONS ON TWO-DIMENSIONAL ECHOCARDIOGRAPHY IN PATIENTS WITH KAWASAKI DISEASE

INTRODUCTION: In Kawasaki disease, we have detected linear shadows inside large- or moderate-sized coronary arterial lesions (CALs) on high-resolution two-dimensional echocardiography (2DE). OBJECTIVE: For this study, we wanted to investigate the origin and clinical significance of these linear shadows compared with findings on coronary angiography (CAG), MRI, and intravascular ultrasound. RESULTS: Linear shadows were detected in 11 CALs on high-resolution 2DE in 9 patients with Kawasaki disease. The outer diameters of CALs on 2DE (7.0 ± 2.1 mm) were larger than those on CAG (4.4 ± 1.6 mm), whereas the inner diameters between linear shadows (3.9 ± 1.6 mm) were almost equal to the diameters of CALs on CAG. There was a statistically significant positive correlation (y = 0.99x − 0.10; r2 = 0.77) between the diameters of CALs on CAG and the inner diameters between linear shadows on 2DE. A thickened intima was revealed in the same regions that showed linear shadows on 2DE, in 7 of 11 lesions on MRI, and in all 4 lesions on which intravascular ultrasound was performed. In 3 patients who had been followed up over 3 years, linear shadows inside CALs on 2DE persisted, and the diameter between linear shadows was almost consistent with the diameter of CALs on CAG. CONCLUSIONS: These results suggest that linear shadows inside CALs on 2DE would reflect the existence of a thickened intima. We expected that following up the changes of linear shadows inside CALs was useful for noninvasive evaluation of coronary arterial remodeling such as intimal hypertrophy or stenotic change.

Abstract 2764: The Advantages of using Multi-slice Spiral Computed Tomography to Evaluate Serious Coronary Complications in Adolescents after Kawasaki Disease

Objectives We identified novel multi-slice spiral computed tomography (MSCT) findings in adolescents after Kawasaki disease that could not be detected by coronary angiography (CAG). Methods We studied 18 patients who had suffered from serious coronary arterial lesions after Kawasaki disease (mean age: 21.7 years; range: 13 to 34 years). Seventeen patients had stenotic lesions, and all had coronary aneurysms. MSCT was performed using a Siemens SOMATOM Volume Zoom (4-detector row) or a Toshiba Aquillion 16 (16-detector row). The detection of coronary calcification, stenotic lesion, and intimal hypertrophy was applied to all coronary arteries in MSCT and compared to CAG. Results Of the 18 patients, there were 11 (61%) in whom novel findings were detected by MSCT. Coronary calcifications were found in 11 of the 18 patients (61%) by MSCT. Five patients had concentric calcified aneurysms, 4 had eccentric calcified aneurysms, and the other 2 had mixed calcified aneurysms. Coronary stenotic lesions were present in 6 of the 18 patients (33%) with calcified aneurysms. There were 2 patients who had intimal hypertrophy (11%). One patient had intimal hypertrophy along the left main trunk with a giant calcified aneurysm along the left anterior descending artery. Two patients had severe stenoses just distal to giant calcified aneurysms that were regarded as false positive findings, which were identified as mild stenoses by CAG. Conclusions MSCT offers advantages over CAG in the evaluation of calcified aneurysms and intimal hypertrophy, and has the potential to become a diagnostic modality for coronary intervention in adolescents after Kawasaki disease.

Type 1 neurofibromatosis complicated by pulmonary artery hypertension: a case report

We describe the case of a patient with neurofibromatosis type 1 (NF1) complicated by severe pulmonary aterial hypertension (PAH); only seven cases have been reported on this association so far, and PAH seems to be related to the vascular involvement of neurofibromatosis. The histology of our patient's lung tissue showed thickening of arteries and veins by medial and/or intimal hypertrophy and fibrosis. In order to exclude a familiar PAH, the analysis of the bone morphogenetic protein receptor 2 gene was carried out, but no mutations were found. On the basis of histological findings and of the results of genetic study we believe that PAH was a complication of NF1 in our patient and we suggest to screen patients with NF1 for the presence of PAH by means of trans-thoracic echocardiogram.

Widespread vascular production of C-reactive protein (CRP) and a relationship between serum CRP, plaque CRP and intimal hypertrophy

Objectives Evidence of local vascular production and a relationship between serum hsCRP levels and tissue expression of CRP in subjects with vascular disease would support a direct role for CRP in atherosclerosis. Methods and results Vascular tissue from subjects undergoing coronary artery bypass grafting surgery (CABGS) ( n = 28) and carotid endarterectomy (CEA) ( n = 25) were studied. Histological samples were assessed for intima–media ratio (IMR) and CRP by immunohistochemistry. CRP mRNA was quantified by real-time polymerase chain reaction. CRP mRNA was seen in all plaques, non-atherosclerotic artery and atrium but no difference in mRNA expression was seen between plaque and non-atherosclerotic tissue. Serum hsCRP correlated with IMR ( r = 0.64, p = 0.001) in non-atherosclerotic arteries and with plaque CRP staining ( r = 0.57, p = 0.009) independent of age, BMI, lipids, diabetes and blood pressure. In a separate patient series, serum hsCRP was measured in aortic and coronary sinus blood from subjects undergoing CABGS or angiography ( n = 54). There was a coronary circulation hsCRP gradient ([mean ± S.E.M.] aortic CRP 4.3 mg/l ± 0.8 versus coronary sinus 5.8 ± 1.2 mg/l, p < 0.05). Conclusions Widespread vascular CRP mRNA expression, a correlation between serum hsCRP, intimal hypertrophy and plaque CRP, and a coronary hsCRP gradient suggest vascular secretion may contribute to serum CRP levels.

Sildenafil, a PDE5 inhibitor, in the treatment of pulmonary hypertension

Pulmonary hypertension is a devastating disorder, characterized by vascular proliferation, intimal hypertrophy and vasoconstriction. In this disorder, alterations in the nitric oxide pathway have borne out to be important in not only vascular proliferation, but also in the maintenance of vascular tone. After synthesis by soluble guanylate cyclase, cGMP effects vasodilation via protein kinase G and other mediators, and is hydrolyzed by phosphodiesterases (PDEs). PDE5 is abundantly expressed in the mammalian lung and its inhibition by sildenafil has been demonstrated to improve pulmonary vascular physiology in vitro and in vivo animal models of pulmonary hypertension. Recent human data has confirmed the efficacy of sildenafil in therapy for humans with pulmonary arterial hypertension. The following review will discuss the underlying basic science supporting the use of sildenafil, as well as human evidence supporting the critical role of this drug in therapy of patients with pulmonary hypertension.

Ulcère veineux de la main secondaire à une fistule artérioveineuse thérapeutique

An arteriovenous fistula of the arm for hemodialysis needs to last long and provide easy access for puncture. A 50 year-old woman, with type 2 diabetes complicated by chronic renal failure, presented with an ulcer on the dorsum of the right hand that had developed over the past year. Humeral artery to basilica vein, side-to-side, arteriovenous fistula in the right arm was created in 1996. In 1999, she received a renal transplant. In 2002, she developed a deep ulcer on the dorsum of the right hand that progressed over one year, without improvement good local treatment. Doppler echography and a fistulography revealed proximal stenosis of the basilica vein, and a less restricted distal stenosis before the shunt. A venous ulcer on the dorsum of the hand due excessive venous pressure in the draining area. The complications of arteriovenous fistulas can be severe. Arterial stenosis is frequent and is the consequence of intimal hypertrophy. Chronic ischemia symptoms can be observed, but the hemodynamic loss is usually asymptomatic. When clinical signs are noisy emergency surgery is required. Venous stenosis is responsible for ischemia through venous overload, leading to edema of the arm, and rarely to venous-ulcer type trophic disorders as seen in this patient. Screening for stenosis on the vascular vein network must be systematic before creating an arteriovenous fistula.

Dialysis Rounds A Dialysis Case Presentation and Discussion Edited by Roger A. Rodby : Long‐Term Intravenous Sodium Thiosulfate in the Treatment of a Patient with Calciphylaxis

ABSTRACTCalciphylaxis is a disabling and life‐threatening complication that primarily affects patients who are dialysis dependent. This disease entity is characterized by calcification, intimal hypertrophy, and thrombosis of small vessels, which results in necrotizing, nonhealing ulcers. The development of these lesions portends a grim prognosis, as they are often accompanied by severe and sometimes fatal infectious complications. Although several strategies aimed at treating and preventing this affliction have been reported in the literature, the outcome for most patients with calciphylaxis remains quite poor. We describe an anuric hemodialysis patient who developed severe calciphylaxis that proved refractory to conventional treatment. Following extensive debridement of several wounds, intravenous sodium thiosulfate was utilized as an adjunctive therapy four times a week. Within 6 months, excellent wound healing ensued as well as a dramatic improvement in the lesions that were not previously resected. Aside from occasional nausea, these treatments were well tolerated, despite the development of an anion gap metabolic acidosis. After 34 months of continued treatment the patient remains free from disease recurrence and has demonstrated no untoward effect of prolonged therapy. In an effort to delineate the pharmacokinetics of this drug in a hemodialysis patient, serum thiosulfate levels were obtained 15 minutes after infusion as well as before and after subsequent dialysis treatments. Consistent with prior studies in anuric canines, we found measurable quantities of the drug more than 50 hours after treatment, in addition to a markedly elevated half life of 478 minutes. However, given the lack of significant toxicity, as well as a dramatic clinical improvement, we feel that sodium thiosulfate may have an important adjunctive role in the treatment of calciphylaxis in dialysis patients.

Overview of renal bone disease: Causes of treatment failure, clinical observations, the changing pattern of bone lesions, and future therapeutic approach: Management of comorbidities in kidney disease in the 21st century: Anemia and bone disease

Divalent ions, metabolism abnormalities, and hyperparathyroid bone disease noted in patients with chronic kidney disease (CKD) develop early in the course of renal insufficiency. In the last two decades, therapy has focused mostly in treating the bone lesion as well as controlling the secondary hyperparathyroidism. However, recent large epidemiologic studies have highlighted the importance of both hyperphosphatemia and an increase in the calcium burden as major factors leading to the high mortality rate of end-stage renal disease (ESRD) patients [1–3]. Furthermore, a recent study strongly suggests the high mortality rate may be due to an increase in cardiac events [4]. In the present manuscript, the causes for the failure of the original therapeutic goals will be discussed first; the changing pattern in the bone lesions will be assessed second; and third, future therapeutic approaches will be explored, with special emphasis in early therapy and avoiding the cardiovascular abnormalities recently noted in CKD patients.

Altered myocardial flow reserve and endothelial function late after Kawasaki disease

Objectives Coronary arterial lesions after Kawasaki disease (KD) may cause coronary endothelial dysfunction as the result of intimal hypertrophy. Our purpose was to assess myocardial flow reserve (MFR) and endothelial function in various myocardial regions after KD by using positron emission tomography. Study design Twenty-seven patients, 17.2 ± 3.2 years of age, who had KD at 1.9 ± 1.4 years, and 12 normal healthy subjects, 26.5 ± 3.4 years of age, were evaluated by means of myocardial blood flow (MBF) with 15O-water positron emission tomography. MFR was estimated by MBF changes under adenosine triphosphate infusion and endothelial function by MBF changes under cold pressor testing. The left ventricle was divided into three coronary territories. Ten stenotic regions, 20 aneurysmal regions, 30 regressed aneurysmal regions, and 21 regions without coronary arterial lesions were compared with 36 control regions of the normal volunteers. Results MBF at rest was similar in each region. Hyperemic blood flow and MFR in each region after KD was significantly lower than those in the regions of normal volunteers. MBF during cold pressor testing was significantly reduced in each region after KD, as compared with no change in the control regions. Conclusions Our study indicates impaired MFR and endothelial function regardless of coronary artery status after KD. (J Pediatr 2003;142:149-54)

Intimal Changes in the Cephalic Vein of Renal Failure Patients before Arterio-Venous Fistula (AVF) Construction

Native cephalic vein remains the superior dialysis conduit, even thirty years after it was first described. However, up to 37% of hemodialysis patients develop progressive stenosis in the venous circuit of arterio-venous fistula (AVF), which may later cause thrombosis and occlusion. To study the pre-existing morphological changes in the wall of the cephalic vein before AVF construction, we collected 23 cephalic vein specimens from 3 normal, young trauma and twenty renal failure patients. The samples were collected at the time of vascular repair in the first group and AVF construction in the second group. Sections were prepared and stained for both light and transmission electron microscopy (TEM) examination. Compared with normal cephalic vein, all pre-access cephalic veins showed thickening of the wall and intimal hyperplasia. Other changes were loss of internal elastic lamina in 9 (45%) patients, loss of endothelial cell layer in 6 (30%), inflammatory cell infiltration of the wall in 5 (25%), mural calcification in 3 (15%) and telangiectasia in 2 (10%). Other ultrastructural changes observed were intimal hypertrophy, degeneration and loss of the endothelial cells, degeneration and fraying of smooth muscle cells (SMCs) and loss of wall components into the lumen. In conclusion, most of the apparently normal cephalic veins of renal failure patients showed morphological abnormalities at the time of AVF construction, which may well influence the outcome of shunts in terms of future stenosis and failure. It seems likely that the later development of AVF stenosis may be the result of pre-existing disease rather than the direct insult of arterialization.

Treatment of the Ischemic Hand in Frostbite By Revascularization with Interpositional Vein Graft and Digital Palmar Sympathectomy: A Case Report

In severely ischemic hands where the microcirculation is not amenable to reconstruction, there is evidence that palmar digital sympathectomy has salutary effects. This report describes the case of a patient with a painful, ulcerated, ischemic hand secondary to ulnar artery stenosis, generalized vasospasm and intimal hypertrophy that resulted from cold injury. Surgical treatment involved an interpositional vein graft replacing a thrombotic segment of the ulnar artery and concomitant palmar digital sympathectomy. The coupling of these two microvascular procedures completely relieved the patient's symptoms, increased total blood flow and improved the vascular function of the hand. The combination of reconstruction of an occluded vessel with peripheral sympathectomy in treating difficult cases of ischemic hand injury is recommended.

Fluorescence spectrum analysis of atherosclerotic plaque using doxycycline.

Using doxycycline (DOXY), fluorescence spectrum analysis was performed on arteriosclerotic lesions, and the efficacy of this method was examined in basic and clinical studies. In the basic study, DOXY 50 mg was administered intravenously to arteriosclerotic rabbits, and the thoracoabdominal aorta removed. Fluorescence spectral analysis was performed on each specimen, and the fluorescence spectral pattern, peak intensity and degree of intimal hypertrophy were studied. In the clinical study, DOXY 200 mg was administered intravenously to 6 human subjects with stable angina and coronary arterial stenosis of greater than 90%, and coronary angiography, coronary angioscopy and fluorescence spectral analysis were performed. DOXY accumulation in the arteriosclerotic intima of rabbit aortae was confirmed. The fluorescence spectrum was monomodal, peaking at around 532 nm. In the noncalcification group, significant correlation was observed between peak intensity and arteriosclerotic intimal thickness. Using DOXY as a fluorescent marker, it was possible to assess the level of arteriosclerotic intimal hypertrophy. Clinically, it was possible to obtain the DOXY spectrum of the coronary arteries.

Protective Effects of Iganidipine on Morphological and Functional Changes of Arteries in Hypertensive Dahl Rats.

BACKGROUND: This study was performed to examine the protective effects of iganidipine, a new water-soluble calcium antagonist, on the morphological and functional changes of arteries in Dahl salt-sensitive (Dahl-S) rats. METHODS AND RESULTS: Vehicle and iganidipine were administered orally to Dahl-S rats fed a high-salt diet (HSD) for 8 weeks. Aorta, superior mesenteric arteries (SMA), and peripheral mesenteric arteries (PMA) were examined light-microscopically or electon-microscopically. Relaxant responses of isolated aorta and SMA were recorded isometrically. In rats fed HSD, blood pressure was markedly increased. Light microscopy showed intimal and medial hypertrophy, periarteritis, and narrowed arterial lumen in the PMA. Transmission and scanning electron microscopy or light microscopy showed medical thickness in the aorta and SMA and hypertrophy of endothelial cells and dilatation of the subendothelial space only in the aorta. In the SMA, both endothelium-dependent relaxation (EDR) and endothelium-independent relaxations (EIR) were reduced to a similar extent. In the aorta, the EDR was more markedly attenuated than the EIR. Iganidipine at 3 mg/kg/day showed a 24-h sustained hypotensive effect and completely prevented the morphological and functional changes in both arteries. Iganidipine at 1 mg/kg/day, which lowered blood pressure only for several hours, decreased the injuries in PMA and aortic endothelium and moderately restored the EDR in the aorta. Iganidipine at 0.3 mg/kg/day had no effects. CONCLUSIONS: In Dahl-S rats fed an HSD, iganidipine completely prevented all the changes at a sustained-hypotensive dose and prevented the injuries of PMA and aortic endothelium and the reduction of EDR in the aorta at a nonsustained hypotensive dose. Nonhemodynamic effects of iganidipine may be partly involved in its protective effects against arterial injuries.

Intimal hypertrophy and tunica media degeneration of injured arteries in electrical burns

This study describes the histologic findings of injured arteries after electrical burns. These findings are shown to correlate with the clinical findings of soft tissue necrosis and delayed bleeding. Eight patients with severe electrical injuries who underwent amputations of extremities were studied. Thickening of the tunica intima and degeneration of the tunica media, associated with small artery occlusion, were evident in the arteries at the transition zone between severely injured and grossly normal areas.

The impact of angiotensin converting enzyme inhibitors on the arterial wall.

There is recent interest in the possibility that angiotensin converting enzyme inhibitors (ACE inhibitors) may reduce the damage inflicted on the arterial wall by common cardiovascular risk factors such as hypertension, hyperlipidaemia and ageing. The efficacy of these drugs in blood pressure reduction is accepted, but whether there is an excess benefit on arterial structure and function, conferred by use of ACE inhibitors over more traditional antihypertensives, is still under debate. There is also evidence in animal models to suggest that ACE inhibition is effective in reduction of arterial damage due to experimental hyperlipidaemia. ACE inhibitors not only reduce the conversion of angiotensin I and angiotensin II, which can interact with the sympathetic nervous system, but also prevent the degradation of bradykinin. This means that ACE inhibitors have several potential mechanisms through which they could suppress intimal hypertrophy and prevent endothelial dysfunction, which is believed to precede arteriosclerosis in man. Although much further work is needed to clarify the mechanism underlying the beneficial effects on the arterial wall of this group of drugs, they do appear to have significant potential in the effort to reduce cardiovascular mortality and morbidity, especially in high risk groups.

Chronic encapsulated expanding hematoma in association with gamma knife stereotactic radiosurgery for a cerebral arteriovenous malformation

The authors report a rare case of a patient with a chronic encapsulated expanding hematoma and progressive neurological deterioration who presented 2 years after gamma knife radiosurgery for a cerebral arteriovenous malformation (AVM). A tough capsule containing multiple layers of organized hematoma resulting from previous bleeding was confirmed surgically. Histological examination revealed that the capsule consisted of a dense collagenous outer layer and a granulomatous newly vascularized inner layer with marked fibrosis. Hemosiderin deposits were frequently observed in the inner layer, which suggested recurrent minor bleeding from fragile vessels in this layer. An AVM was found in the hematoma, which had degenerated as the result of radiosurgery. A cross-section of the abnormal vessels showed various stages of obliteration due to intimal hypertrophy. The clinical course, radiological features, and histological findings in this case were compatible with those of previously reported chronic encapsulated hematomas. A possible mechanism of hematoma formation and its expansion are discussed.

Chronic pulmonary infection caused by Mycoplasma pneumoniae leading to pulmonary arteriole remodeling and pulmonary hypertension in rats.

The pulmonary arteriole remodeling in Wistar rats with respiratory infection induced by mycoplasma pneumoniae was observed using light microscopy and morphometry. The pulmonary artery pressure (PAP) and index of right ventricular hypertrophy (RVHI) were measured. The intimal and medial hypertrophy can be seen in the pulmonary arterioles, leading to vessel wall thickening and narrowing of the lumina. The total number of the pulmonary arterioles decreased (P < 0.01), and both pulmonary hypertension (Ppa 4.11 +/- 0.19 kPa) and right ventricular hypertrophy (RVHI = 34.96 +/- 3.91%) occurred. In addition, an interstitial pulmonary fibrosis (IPF) was found, in which the content of collagen in the lung tissue changed, i. e., type I collagen increased whereas type III one decreased, and the ratio of type I collagen to type III one increased. It suggested that respiratory infection induced by repeated MP may result in remodeling of pulmonary arterioles and are closely related to pulmonary hypertension.

Gamma knife radiosurgery for cerebral arteriovenous malformations: An autopsy report focusing on irradiation-induced changes observed in nidus-unrelated arteries

In radiosurgical treatment for an arteriovenous malformation (AVM), the effects of irradiation on the intranidal and perinidal angioarchitectures have seldom been analyzed histologically. An autopsy case is reported, studying an AVM treated by gamma knife radiosurgery. Postmortem studies following AVM-unrelated death were performed after a 2-year angiography had demonstrated complete nidus obliteration. Irradiation-induced changes were also observed in surrounding nidus-unrelated arteries and the choroid plexus, both of which were within the irradiation target. Microscopic studies were performed using a coronal section of the brain including the center of the AVM, on which the percent isodose volume gradient, corrected with a magnification rate, was superimposed. This study disclosed that intimal hypertrophy can occur in a normal, AVM-unrelated pial artery due to irradiation of 10 Gy or more and that more remarkable intimal hypertrophy with fragmentation of the elastic laminae, or even complete occlusion, can occur in these arteries with 25 Gy. Similarly, irradiation-induced degeneration was present in the choroid plexus, which had been exposed to doses varying from 10 Gy to 25 Gy. A normal surrounding blood vessel may also be affected by high-dose, single-fraction irradiation though the abnormal vessels have been reported to be more susceptible.

Progressive ischemic gangrene in dialysis patients: a clinicopathological correlation.

The syndrome of progressive ischemic gangrene (PIG) of the extremities was examined over 3.5 years in patients undergoing maintenance dialysis (MD) in Kuwait and was compared to that in a similar age group (> 40 years) in the general population. The incidence of PIG in MD patients was 15.4/1000 person years of observation (PYO) versus 0.086/1000 PYO in the general population. Patients with diabetes mellitus were found to be at particular risk. PIG developed in 41.4/1000 PYO of diabetic patients who received MD, compared to 7.1/1000 in nondiabetic patients on MD and 0.14/1000 in diabetics without renal disease. The clinical, biochemical, radiological, and histological findings in the 8 patients who developed PIG while on maintenance dialysis (MD) are presented. Two patients had severe hyperparathyroidism and their histological findings were consistent with systemic calciphylaxis. Histological examination, in the remaining patients, showed severe calcified atherosclerosis. Intimal hypertrophy was common especially in patients with long duration on dialysis. The three lesions produced a variable degree of luminal narrowing and were associated with arterial thrombosis. None of the patients showed evidence of iron deposition even in those with systemic calciphylaxis and excessive iron stores. Our study indicated a high incidence of PIG in patients undergoing MD, especially in those with diabetes mellitus. These findings constitute a cogent argument in favor of early parathyroidectomy in selected cases and concern with long-term consequences of atherosclerosis in this patient population.

Pulmonary vasculature in idiopathic dilated cardiomyopathy: a morphometric study.

The pulmonary vascular alterations of seven patients with idiopathic dilated cardiomyopathy (IDC) were morphometrically examined, and the relation between the vascular alterations and morphological status of the hearts was studied. Most patients with IDC showed not only fibrous thickening of small pulmonary veins but also intimal circumferential fibrosis and medial hypertrophy of small pulmonary muscular arteries to various degrees. The histological features of the pulmonary vessels were compatible with hypertensive vascular changes observed in patients with mitral stenosis. There was a significant correlation between medial hypertrophy of the pulmonary muscular arteries and right ventricular hypertrophy. The pulmonary vascular changes in IDC were always associated with left atrioventricular dilatation, but were only found in patients with prominent hypertrophy of the left ventricles. Medial hypertrophy of the pulmonary muscular arteries was related more to left ventricular hypertrophy than to left ventricular dilatation. These findings suggest that the pulmonary vascular changes in IDC are caused by venous pulmonary hypertension, which may be developed at the late stage when left ventricular hypertrophy predominates.