Enhanced pulmonary leptin expression in patients with severe COPD and asymptomatic smokers.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is characterised by an abnormal inflammatory reaction of the lungs involving activation of epithelial cells. Leptin is a pleiotropic cytokine important in the regulation of immune responses via its functional receptor Ob-Rb. This study was undertaken to test the hypothesis that severe COPD is associated with increased leptin expression in epithelial cells. METHODS: Immunohistochemistry for leptin was performed on peripheral lung specimens from 20 patients with COPD (GOLD stage 4), 14 asymptomatic ex-smokers and 13 never smokers. Leptin and Ob-Rb mRNA expression were determined by rtPCR in cultured primary bronchial epithelial cells and primary type II pneumocytes. NCI-H292 and A549 cell lines were used to study functional activation of leptin signalling. RESULTS: Leptin immunoreactivity in lung tissue was observed in bronchial epithelial cells, type II pneumocytes, macrophages (tissue/alveolar) and interstitial lymphocytic infiltrates. rtPCR analysis confirmed pulmonary leptin and Ob-Rb mRNA expression in primary bronchial epithelial cells and pneumocytes. Leptin-expressing bronchial epithelial cells and alveolar macrophages were markedly higher in patients with severe COPD and ex-smokers than in never smokers (p<0.02). Exposure of cultured primary bronchial epithelial cells to smoke resulted in increased expression of both leptin and Ob-Rb (p<0.05). Leptin induced phosphorylation of STAT3 in both NCI-H292 and A549 cells. CONCLUSIONS: Leptin expression is increased in bronchial epithelial cells and alveolar macrophages of ex-smokers with or without severe COPD compared with never smokers. A functional leptin signalling pathway is present in lung epithelial cells.

Analysis of the relative deformation of lung lobes before and after surgery in patients with NSCLC.

An accurate assessment of the extent of the tumor is critical for successful local treatment of lung cancer by surgery and/or radiotherapy. Guidelines to establish the extent of treatment margins may be derived from correlation studies between pre-treatment imaging and histopathology. Deformations occur, however, between in-vivo CT imaging and ex-vivo pathology due to the softness of lung tissue and pathology processing. The first aim of this study was to quantify these deformations in tissue around non-small cell lung cancer. The second aim was to explore factors associated with the magnitude of the deformations. The study was performed in 25 patients who underwent lobectomy after preoperative CT. Non-rigid registration was employed to evaluate tissue deformations around the gross tumor volume (GTV), taking into account potential differences in elasticity between tumor and healthy lung tissue. Tissue was found to be compacted by approximately 60% depending on circularity of the tumor and orientation of the specimen on the pathology table during processing. The deformations give rise to potential underestimation of the treatment margins in pathology studies that do not take this aspect into account.

Large cell neuroendocrine carcinoma with a solitary brain metastasis and low Ki-67: a unique subtype.

INTRODUCTION: Stage IV large cell neuroendocrine carcinoma (LCNEC) of the lung generally presents as disseminated and aggressive disease with a Ki-67 proliferation index (PI) 40-80%. LCNEC can be subdivided in two main subtypes: the first harboring TP53/RB1 mutations (small-cell lung carcinoma (SCLC)-like), the second with mutations in TP53 and STK11/KEAP1 (non-small-cell lung carcinoma (NSCLC)-like). Here we evaluated 11 LCNEC patients with only a solitary brain metastasis and evaluate phenotype, genotype and follow-up. METHODS: Eleven LCNEC patients with solitary brain metastases were analyzed. Clinical characteristics and survival data were retrieved from medical records. Pathological analysis included histomorphological analysis, immunohistochemistry (pRB and Ki-67 PI) and next-generation sequencing (TP53, RB1, STK11, KEAP1 and MEN1). RESULTS: All patients had N0 or N1 disease. Median overall survival (OS) was 12 months (95% confidence interval (CI) 5.5-18.5 months). Mean Ki-67 PI was 59% (range 15-100%). In 6/11 LCNEC Ki-67 PI was ≤40%. OS was longer for Ki-67 ≤40% compared to >40% (17 months (95% CI 11-23 months) vs 5 months (95% CI 0.7-9 months), P = 0.007). Two patients were still alive at follow-up after 86 and 103 months, both had Ki-67 ≤40%. 8/11 patients could be subclassified, and both SCLC-like (n = 6) and NSCLC-like (n = 2) subtypes were present. No MEN1 mutation was found. CONCLUSION: Stage IV LCNEC with a solitary brain metastasis and N0/N1 disease show in the majority of cases Ki-67 PI ≤40% and prolonged survival, distinguishing them from general LCNEC. This unique subgroup can be both of the SCLC-like and NSCLC-like subtype.

Prevalence and prognostic value of PD-L1 expression in molecular subtypes of metastatic large cell neuroendocrine carcinoma (LCNEC).

BACKGROUND: Pulmonary large cell neuroendocrine carcinoma (LCNEC) is a rare tumor with high mutational burden. Two subtypes of LCNEC are recognized, the co-mutated TP53 and RB1 group and the TP53 and STK11/KEAP1 group. We investigated PD-L1 and CD8 expression in a well characterized stage IV LCNEC cohort and compared expression in the two subtypes. METHODS: Immunohistochemical (IHC) analysis for PD-L1 and CD8 was performed on pathological reviewed pretreatment tumor samples for 148 stage IV LCNEC. Data about targeted next generation sequencing (TNGS) (TP53, RB1, STK11, KEAP1) and IHC for RB1 were available for most tumors. IHC staining for PD-L1 (DAKO 28-8) was performed and scored positive if tumors showed ≥1% membranous staining. CD8 was scored for intra-tumor T-cells and stromal cells. RESULTS: PD-L1 IHC expression data could be generated in 98/148 confirmed LCNEC samples along with RB1 IHC (n = 97) of which 77 passed quality control for TNGS. PD-L1 expression was positive in 16/98 cases (16%); 5 (5%) with ≥50%. PD-L1 expression was equal in RB1 mutated and RB1 wildtype tumors. None of STK11 mutated tumors (n = 7) expressed PD-L1. PD-L1 expression was correlated with superior overall survival (OS), hazard ratio 0.55 ((95% Confidence Interval 0.31-0.96), p = 0.038). Intra-tumor CD8 was associated with PD-L1 expression (p = 0.021) and stromal and intra-tumor CD8 were correlated with improved OS (p = 0.037 and p = 0.026 respectively). CONCLUSIONS: PD-L1 expression was positive in 16% of stage IV LCNEC tumors. This was independent of molecular subtype but associated with CD8 expression. In LCNEC patients with PD-L1 and/or CD8 expression superior OS was observed.

DLL3 expression in large cell neuroendocrine carcinoma (LCNEC) and association with molecular subtypes and neuroendocrine profile.

OBJECTIVES: For stage IV pulmonary large cell neuroendocrine carcinoma (LCNEC), the only therapeutic option is palliative chemotherapy. DLL3 is a new therapeutic target, which seems to be often expressed in SCLC and LCNEC. It has recently been reported that DLL3 mRNA expression is particularly upregulated in the LCNEC subgroup with STK11/KEAP1 and TP53 co-mutations, in contrast to lower expression levels in RB1 and TP53 co-mutated LCNEC. Our aim was to investigate DLL3 protein expression in stage IV LCNEC and correlate data with mutational profiles (i.e.STK11/KEAP1/RB1), immunostaining results (pRb, NE markers) and clinical characteristics. MATERIALS AND METHODS: Immunohistochemical analysis for DLL3 (SC16.65) and ASCL1 (SC72.201) was performed on 94 and 51 FFPE tissue sections, respectively, of pathologically reviewed stage IV LCNEC. DLL3 and ASCL1 were scored positive if ≥1% of the tumor cells showed cytoplasmic/membranous or dotlike (DLL3) or nuclear (ASCL1) immunostaining. Data were correlated with available sequencing (TP53, RB1, STK11, KEAP1), immunostaining (pRb, NE markers) and clinical data. RESULTS: DLL3 was expressed in 70/94 (74%) LCNEC, 56 (80%) of which showed cytoplasmic/membranous staining. Median H-score was 55 (interquartile range 0-160). DLL3 staining was not different in pRb immunohistochemistry negative and positive patients (DLL3+ in 53/70 (76%) vs. 14/21 (67%), p = 0.409) or RB1 mutated and wildtype patients (DLL3+ in 27/34 (79%) vs. 23/33 (70%), p = 0.361). Nevertheless, 6/6 (100%) STK11 mutated, 10/11 (91%) KEAP1 mutated and 9/9 (100%) TP53 wildtype tumors were DLL3+ . Furthermore, DLL3 expression was associated with expression of ASCL1 and at least 2 out of 3 neuroendocrine markers. CONCLUSION: The high percentage (74%) of DLL3 expression in stage IV LCNEC denotes the potential of DLL3 targeted therapy in this patient group.

Histological assessment of preimplantation biopsies may improve selection of kidneys from old donors after cardiac death.

Kidneys from old donors after cardiac death (DCD) may increase the donor pool but the prognosis of these kidneys is unsatisfactory. To improve these results, we retrospectively evaluated the diagnostic utility of published selection algorithms for old donor kidneys. We studied all DCD kidney transplantations between January 1, 1994 and July 1, 2005 at our institution (n = 199). Selection algorithms were evaluated in the subset of kidney transplantations from donors aged 60 years or older (n = 52). For histological assessment of kidney biopsies, glomerulosclerosis, tubular atrophy, interstitial fibrosis and vascular narrowing were blindly scored. Functional kidney weight was calculated as renal mass multiplied by the fraction of nonsclerosed glomeruli. Graft function and survival of kidneys from DCD aged 60 years or older were inferior to those from younger DCD. Histological scores were associated with kidney function and graft survival of old DCD kidney transplantations. Functional kidney weight was associated with kidney function but not graft survival, while donor glomerular filtration rate (GFR), donor age and machine perfusion characteristics were associated with neither of the clinical outcomes of interest. We conclude that histological assessment of preimplantation biopsies may improve the selection of kidneys from old DCD and may therefore contribute to expansion of the donor pool.

Primary monophasic mediastinal, cardiac and pericardial synovial sarcoma: a young man in distress.

A 19-year-old male was admitted because of exertional dyspnoea. The imaging studies revealed epicardial, pericardial and mediastinal masses. The tumours could not be resected through a minor thoracotomy, only biopsies could be taken. Analyses led to the final diagnosis of a monophasic synovial sarcoma. The patient preferred a conservative and palliative approach. Three months later he died at home. Autopsy demonstrated dramatic extension of the tumour masses. We conclude this report with a discussion on primary cardiac tumours. (Neth Heart J 2007;15:226-8.).

Purpura fulminans mimicking toxic epidermal necrolysis - additional value of 16S rRNA sequencing and skin biopsy.

Both purpura fulminans and toxic epidermal necrolysis (TEN) are rare and life-threatening disorders with a high mortality. We present a case of suspected rapidly progressive, severe pneumococcal sepsis-induced purpura fulminans complicated by multiple organ failure, severe epidermolysis and cutaneous necrosis. We show the diagnostic challenge to differentiate between purpura fulminans and TEN, as the extensive epidermolysis in purpura fulminans may mimic TEN and we highlight the additional value of repeated skin biopsies and 16S rRNA gene sequencing.

Proliferation and extracellular matrix synthesis of smooth muscle cells cultured from human coronary atherosclerotic and restenotic lesions.

OBJECTIVES: The purpose of this study was to examine the proliferative capacity and extracellular matrix synthesis of human coronary plaque cells in vitro. BACKGROUND: Common to both primary atherosclerosis and restenosis are vascular smooth muscle cell proliferation and production of extracellular matrix proteins. The applicability to humans of experimental animal models of these processes has been questioned. METHODS: Primary atherosclerotic and restenotic lesions were excised by percutaneous directional coronary atherectomy in 93 patients. Smooth muscle cells were cultivated by an explant technique and identified by their morphology in culture, ultrastructural features under electron microscopy and immunostaining using monoclonal antibodies to smooth muscle cell alpha-actin. Proliferation in secondary culture was assessed with growth curves and the synthesis of collagen and sulfated glycosaminoglycans by the incorporation of 3H-proline and 35S-sulfate, respectively. These studies were also performed in cells derived from human umbilical artery media. RESULTS: Success rates for primary (45%) and secondary (12%) culture of coronary cells were not influenced by clinical variables or lesion category. Primary culture success was improved by the presence of organized thrombus in the plaque and in relation to increased maximal cell density of the atherectomy specimen. Restenotic cells displayed more rapid growth than did cells of primary atherosclerotic origin, which grew in a manner similar to that of umbilical artery cells. Mean calculated population-doubling times for the three cell groups were 52 h (95% confidence interval [CI] 48 to 58 h), 71 h (95% CI 62 to 83 h) and 74 h (95% CI 65 to 84 h), respectively. Restenotic and primary atherosclerotic cells did not differ in the synthesis of collagen ([mean +/- SEM] 0.034 +/- 0.004 vs. 0.033 +/- 0.004 nmol isotope.microgram protein-1, p = NS) or sulfated glycosaminoglycans (11.47 +/- 1.07 vs. 15.37 +/- 3.10 nmol isotope.microgram protein-1, p = NS), but the coronary cells synthesized significantly more collagen and sulfated glycosaminoglycans than did umbilical artery cells (0.019 +/- 0.004 and 5.43 +/- 1.00 nmol isotope.microgram protein-1, respectively, both p < 0.05). CONCLUSIONS: These data indicate that increased smooth muscle cell proliferation contributes to coronary restenosis in humans and support the concept that the extracellular matrix synthesis of adult smooth muscle cells is important to lesion formation.

Balloon angioplasty for the treatment of lesions in saphenous vein bypass grafts.

OBJECTIVES: The purpose of this review is to assess the value and limitations of balloon angioplasty for the treatment of saphenous vein bypass graft obstructions. The potential efficacy of new interventional techniques is discussed. BACKGROUND: Treatment of ischemia due to saphenous vein bypass graft obstructions poses a difficult problem that will be encountered more often as the pool of surgically treated patients continues to accumulate. Reoperation is technically demanding and is associated with high mortality and morbidity rates. Balloon angioplasty may provide a suitable alternative. METHODS: The review proposes a classification of patients with attempted saphenous vein graft angioplasty according to expected early and late outcome based on the data obtained from the relevant published data and personal experience. RESULTS: Angioplasty of a nonocclusive obstruction in a saphenous vein bypass graft has an initial success rate of approximately 90% and is a safe procedure (procedural death rate < 1%, myocardial infarction rate < 4%). The overall average restenosis rate is 42%. Surgical standby is limited and technically difficult. Angioplasty of chronic total occlusions in old grafts is associated with poor initial and long-term results. The long-term clinical results are unfavorable because of the continuing progression of disease in nontreated vein graft segments and native coronary arteries, in addition to the high restenosis rate. New techniques, although promising, have shown neither better initial results nor reduction of restenosis. Stent placement may be useful in longer graft lesions containing friable material. CONCLUSIONS: Patients may be classified into three groups according to expected early and late outcome on the basis of 1) unfavorable graft anatomy, 2) risk of cardiogenic shock in event of acute graft closure, and 3) age of grafts. The three groups are 1) those with an initial high success, low procedural risk and low restenosis rate; 2) those with an initial high success but high procedural risk and moderate to high restenosis rate; and 3) those with a low success, high risk and high restenosis rate. Balloon angioplasty to treat lesions in venous bypass grafts should be considered a palliative procedure, not a long-term solution, for ongoing progression of coronary artery and vein graft disease. The induced high restenosis rate remains a significant problem.

Directional atherectomy for treatment of restenosis within coronary stents: clinical, angiographic and histologic results.

OBJECTIVES: The safety and long-term results of directional coronary atherectomy in stented coronary arteries were determined. In addition, tissue studies were performed to characterize the development of restenosis. METHODS: Directional coronary atherectomy was performed in restenosed stents in nine patients (10 procedures) 82 to 1,179 days after stenting. The tissue was assessed for histologic features of restenosis, smooth muscle cell phenotype, markers of cell proliferation and cell density. A control (no stenting) group consisted of 13 patients treated with directional coronary atherectomy for restenosis 14 to 597 days after coronary angioplasty, directional coronary atherectomy or laser intervention. RESULTS: Directional coronary atherectomy procedures within the stent were technically successful with results similar to those of the initial stenting procedure (2.31 +/- 0.38 vs. 2.44 +/- 0.35 mm). Of five patients with angiographic follow-up, three had restenosis requiring reintervention (surgery in two and repeat atherectomy followed by laser angioplasty in one). Intimal hyperplasia was identified in 80% of specimens after stenting and in 77% after coronary angioplasty or atherectomy. In three patients with stenting, 70% to 76% of the intimal cells showed morphologic features of a contractile phenotype by electron microscopy 47 to 185 days after coronary intervention. Evidence of ongoing proliferation (proliferating cell nuclear antigen antibody studies) was absent in all specimens studied. Although wide individual variability was present in the maximal cell density of the intimal hyperplasia, there was a trend toward a reduction in cell density over time. CONCLUSIONS: Although atherectomy is feasible for the treatment of restenosis in stented coronary arteries and initial results are excellent, recurrence of restenosis is common. Intimal hyperplasia is a nonspecific response to injury regardless of the device used and accounts for about 80% of cases of restenosis. Smooth muscle cell proliferation and phenotypic modulation toward a contractile phenotype are early events and largely completed by the time of clinical presentation of restenosis. Restenotic lesions may be predominantly cellular, matrix or a combination at a particular time after a coronary procedure.

Determinants of coronary reserve in rats subjected to coronary artery ligation or aortic banding.

OBJECTIVE: We investigated whether decreased coronary reserve in hearts after coronary artery ligation or in hearts from rats after aortic banding can be related to remodeling of resistance arteries. METHODS: Maximal coronary flow (absolute flow) and cardiac perfusion (flow corrected for heart weight) were determined in isolated, perfused rat hearts after adenosine or nitroprusside, at 3 and 8 weeks after coronary artery ligation or 4-5 weeks after aortic banding. Perivascular collagen and medial thickness of resistance arteries were determined by morphometry. RESULTS: maximal coronary flow of infarcted hearts had been restored to sham values at 3 weeks. Growth of cardiac muscle mass from 3 to 8 weeks exceeded the increase in maximal coronary flow, leading to a decreased perfusion at 8 weeks. A slight, transient increase in perivascular collagen, but no medial hypertrophy, was found after infarction. After aortic banding perivascular fibrosis and medial hypertrophy led to a decreased maximal coronary flow in both the hypertrophied left and the non-hypertrophied right ventricle. Consequently, perfusion of the left ventricle was most severely reduced. CONCLUSIONS: Reduced maximal perfusion after aortic banding is determined by both cardiac hypertrophy and vascular remodeling. In contrast, during infarction-induced remodeling, reduction of perfusion is not determined by vascular remodeling, but mainly by disproportional cardiac hypertrophy relative to vascular growth.

Assessment of medial thinning in atherosclerosis by intravascular ultrasound.

This study investigated the in vitro (40 MHz) and in vivo (30 MHz) feasibility of intravascular ultrasound to document the influence of atherosclerotic lesions on the typical 3-layered appearance of muscular arteries. The in vitro images of 39 arteries were compared with the corresponding histologic sections. Media and lesion thickness were measured at the areas of minimal and maximal lesion thickness. The median media thickness was 0.8 mm in the absence of a lesion, decreasing to 0.3 mm in the area of maximal atherosclerosis. The ultrasonic data correlated closely with histologic measurements (0.6 and 0.3 mm, respectively). The in vivo study was performed in 29 patients undergoing coronary or peripheral vascular procedures. A total of 150 still-frames were selected for quantitative analysis. The median media thickness was 0.6 mm in the absence of a lesion, decreasing to 0.1 mm in the area with maximal atherosclerosis. This study revealed that intravascular ultrasound imaging accurately determines that media thickness of muscular arteries is inversely related to lesion thickness. In vitro data, verified with histology, can be translated to humans in vivo.

Comparison of intravascular ultrasonic findings after coronary balloon angioplasty evaluated in vitro with histology.

This study investigated whether vascular damage and quantitative changes observed with intravascular ultrasound at the most stenotic site are representative of the ultimate outcome after coronary balloon angioplasty. Atherosclerotic coronary arteries (n = 40) were studied in vitro with intravascular ultrasound. From each vascular specimen, 10 corresponding intravascular ultrasound cross sections obtained before and after balloon angioplasty were selected for comparison with their histologic counterpart. Morphologic and quantitative data obtained from all cross sections were compared with data derived from the most stenotic site. The incidence of vascular damage (i.e., dissection, plaque rupture, and media rupture) at the most stenotic site was lower than that seen for each vascular specimen. The sensitivity of intravascular ultrasound in detecting these morphologic features for each vascular specimen was high for dissection and media rupture (79% and 76%, respectively), and low for plaque rupture (37%). After balloon angioplasty, quantitative changes seen at the most stenotic site were greater than those in all cross sections: free lumen area +58% versus +29%, media-bound area +17% versus +12%, and plaque area reduction -9% versus -6%, respectively. The increase in free lumen area was caused predominantly by media-bound area increase (81%) and to a lesser extent by plaque area decrease (19%). This study revealed that a higher incidence of vascular damage is found when the whole segment is analyzed rather than 1 single cross section at the most stenotic site. Quantitative effects of coronary balloon angioplasty seen with intravascular ultrasound were greater at the most stenotic site than at all cross sections.

Myocarditis as a cause of primary right ventricular failure.

Patients with cardiomyopathy secondary to inflammatory myocarditis usually present with biventricular signs and symptoms. On occasion, the disease may progress focally, with left ventricular involvement predominating. This patient had elevated neck veins, edema, and a dilated right ventricle in the absence of left ventricular abnormalities. At autopsy, diffuse, transmural fibrosis of the right ventricle was found, consistent with end-stage myocarditis, with minimal disease of the left ventricle. This case emphasizes that the clinical manifestations of myocarditis can be limited to the right ventricle and should be considered in the differential diagnosis of right ventricular failure.

Effects of cryopreservation on contractile properties of porcine isolated aortic valve leaflets and aortic wall.

Human semilunar donor heart valves can be stored in banks, awaiting transplantation. To evaluate the result of the preservation protocols, a quantitative description of the tissue is necessary. In this study we investigated in a quantitative way the contractile properties of fresh and cryopreserved porcine isolated aortic heart valve leaflets in response to a number of endogenous vasoactive compounds. The responses of strips of the aortic wall were included for comparison. Contraction was measured isometrically in response to potassium (K+; 100 mmol/L), 5-hydroxytryptamine (1 nmol/L to 100 micromol/L), noradrenaline (1 nmol/L to 100 micromol/L), endothelin-1 (0.01 nmol/L to 0.3 micromol/L), and prostaglandin F(2alpha) (0.1 nmol/L to 10 micromol/L). The pharmacologic parameters E(MAX) (the maximal response expressed as a percentage of contraction to a 100 mmol/L dose of K+) and EC50 (the concentration that produces 50% of the maximal effect) were calculated for every compound (n = 6 to 7 each). We observed that all specimens contracted in response to potassium. Its magnitude in fresh leaflets equaled 1.6 +/- 0.14 mN compared with 26.6 +/- 2.6 mN in fresh aortic wall. Noradrenaline, endothelin-1, and prostaglandin F(2alpha) all caused contraction in valvular leaflets and aortic wall, whereas 5-hydroxytryptamine caused contraction in the valvular leaflets but relaxation in aortic wall. After cryopreservation, the response to K+ amounted to 24% of the response of the fresh specimens in valvular leaflets (n = 25) and 14% in aortic wall (n = 26). The values of E(MAX) and EC50 of the responses to noradrenaline, endothelin-1, and prostaglandin F(2alpha) remained unchanged. Although the physiologic relevance of contraction of valvular leaflets needs further study, its measurement may provide an additional model to verify the consequences of alternative methods of preservation.

Common arterial trunk, uncommon coronary arterial anatomy.

Macroscopic investigation was done in 44 postmortem specimens of hearts with common arterial trunk. In 38 hearts, the normal distribution in left and right coronary arteries was found. Of the coronary orifices, five were pinpoint and three showed a double orifice. The left coronary orifice was positioned in the posterior part of the truncus (p < 0.0001); the right coronary orifice was positioned in the right anterior and lateral part (p < 0.0001). In 19 hearts, coronary orifices were found above sinus level, left coronary orifices more often than right coronary orifices (p < 0.001). In seven hearts, type I truncus was found, in seven type II truncus was found, in 17 the truncus was intermediate between types I and II, in two type III truncus was found. In 11 hearts, the pulmonary artery distribution could no longer be identified. The truncal valve was bicuspid in 11 hearts, tricuspid in 25 hearts, and quadricuspid in eight hearts. The truncal valve showed overriding of 5% to 100%. Malformations of the coronary arteries were found in 28 hearts (64%). In 27 hearts (61%), the coronary arterial anatomy might have had clinical consequences. In nine hearts, coronary arterial orifices were at risk in excision of the pulmonary arteries from the common arterial trunk. The role of the neural crest as an etiologic factor of coronary arterial malformations in common arterial trunk should be taken into account.

Collagen content and distribution in the normal and transplanted human heart: A postmortem quantitative light microscopic analysis.

Endomyocardial biopsies in heart transplant patients offer the opportunity to study the myocardial interstitium in the context of myocardial function. For that purpose endomyocardial biopsies should reliably reflect the composition of the entire myocardium. We determined whether the collagen content in the subendocardial region of the right side of the interventricular septum (site of right ventricular endomyocardial biopsy), in 16 normal and 30 transplanted human hearts, is representative for the entire myocardium. Moreover we determined whether or not the mean collagen content of the myocardium is altered along with the posttransplantation survival time and which factors might contribute to the development of interstitial myocardial fibrosis. Transmural sections of the right and left ventricular free wall and interventricular septum were stained with Sirius red, which specifically stains collagen fibers. Collagen in the subendocardial region and central parts of the myocardium was quantified using a digital image analyzer. In normal hearts the mean collagen content of the subendocardial region of the right side of the interventricular septum (site of right ventricular endomyocardial biopsy) correlates well with the mean collagen content of the right ventricular wall and the center of the interventricular septum, but it does not reliably reflect the mean collagen content of the left ventricular free wall. In transplanted hearts the collagen content at the site of right ventricular endomyocardial biopsy correlates highly with the mean collagen content of the entire myocardium. In transplanted hearts the increase in collagen content is a result mainly of an increase in collagen of the left ventricular free wall. We conclude that in heart transplant patients, right ventricular endomyocardial biopsies have potential value in the analysis of the causes of left ventricular dysfunction. In transplanted human hearts, the posttransplantation survival time correlates positively with the collagen content, and this is attributable mainly to an increase in the collagen of the left ventricular free wall.

Spark erosion myectomy in hypertrophic obstructive cardiomyopathy.

The design features of the cutting electrode and the electrical characteristics of a monopolar electrosurgical device were specially adapted for performing a septal myectomy in patients with hypertrophic obstructive cardiomyopathy. Both the cutting behavior and electrode design were found to facilitate myectomy.

Detection and characterization of vascular lesions by intravascular ultrasound: an in vitro study correlated with histology.

High-frequency intravascular ultrasound (30 and 40 MHz) was applied to study 112 human vascular specimens. The ultrasound images were compared with histologic cross-sections. In 44 out of 58 of the histologically classified muscular arteries, a hypoechoic middle layer was seen in the vessel wall, giving it a three-layered appearance. In 10 arteries, fibrous degeneration of the muscular media resulted in a homogeneous appearance of the vessel walls, whereas atherosclerotic plaque precluded the visualization of the arterial media in four of the arteries. A three-layered appearance was seen in seven of nine histologically classified transitional arteries, and a homogeneous arterial wall was seen in two of the nine. None of the 33 elastic arteries, veins, venous bypass, and Goretex conduits showed a hypoechoic medial layer. Histologically proved fibrous intimal thickening was echographically detected in 32 of 48 specimens (67%). It was noted that these intimal lesions were easier to detect with 40 MHz than with 30 MHz transducers. Hypoechoic areas of lipid deposition were detected in 32 of 36 specimens (89%) and could be distinguished from fibrous plaques. Histologically evident calcium deposits were detected with intravascular ultrasound in 35 of 36 specimens (97%). Measurement of plaque area was only possible in cross sections with a three-layered appearance. Quantitative analysis showed a significantly larger lumen area measured from ultrasonic images (26.3 +/- 21.3 mm2) than from histologic cross-sections (21.8 +/- 16.6 mm2, p less than 0.001), probably because of tissue shrinkage during processing for histology. A significant correlation (r = 0.96, p less than 0.001) between ultrasonic and histologic measurements of lumen areas was observed, with and a negligible interobserver and intraobserver variability. Plaque area and medial thickness correlated well with histology (r = 0.87, p less than 0.001 and r = 0.93, p less than 0.001, respectively). It appears from this in vitro study that intravascular ultrasound is an accurate technique for detection and characterization of atherosclerotic lesions. Vessel lumen area can be measured in most instances, whereas plaque area and medial thickness can only be reliably assessed in muscular arteries in which the hypoechoic media serves as a reference, and shadowing by calcium or attenuation by fibrous plaque components is absent.