Intramyocardial Vessels Research Articles

Rare Case of Hamartoma Mimicking Fibroma and Correlations with Literature

Background: The incidence of primary cardiac tumors ranges from 0.02 to 0.05% in autopsy studies. Hamartomas from mature cardiac myocytes do not present a predilection for age at detection and present a higher prevalence in the left ventricle with the advent of extracorporeal circulation and the advancement of image diagnostic medicine such as echocardiography, computed tomography and magnetic resonance imaging, diagnosis and surgical treatment became more feasible. Objective: To present the case report of a very rare HA with diagnosis by clinical correlation, imaging equipment and microscopy, in order to differentiate it from fibroma. Case: A 63-year-old female patient with a history of chest pain and dyspnea on exertion with progressive worsening six months ago. The echocardiogram presented apical akinesia with an intramyocardial fibro-calcified mass, presenting an intense local coronary vascularization, with a dilated epicardial coronary artery at the tip with 5.0 mm, where the intramyocardial vessels that irrigate the tumor of the apical region originate. A superficial myocardial bridge was visualized by MRI in the middle segment of aDA. The patient underwent endomyocardial biopsy with a suggestive result of Hamartoma of mature cardiac myocytes. Conclusion: Despite the diverse range of cardiac neoplasms, heart tumors are very rare, even more so as the apical Hamartoma and confused with fibroma presented in the present work.

Histological and immunocytochemical investigation of human coronary vessel development with anti-CD34 antibodies

Information about embryonic development of coronary endothelium is the main clue for the creation of new methods in tissue engineering for treatment of ischemic heart diseases. The purpose of the research was to describe human coronary vessels development on early stages of the prenatal ontogenesis. The first step in human coronary vessels development is the formation of endothelium de novo by transformation of some epicardial and, possibly, endocardial cells. The next step is the ingrowth of sinus venosus endothelium in subepicardium over ventricles and atria, which gives rise to the coronary vessels. Only after 7 days does the primitive coronary plexus of the heart communicate with aorta (third step). During this period, some subepicardial vessels invade myocardium and some intramyocardial vessels contact with the heart cavity. Such intercommunications could help in regulation of blood circulation in primitive coronary plexus before establishment of effective contacts between arterial and venous vessels—excess of blood could be discharged directly into the heart cavity. Additional population of CD34+ cells were revealed inside condensed mesenchyme of the conotruncus; it participates in the formation of vasa vasorum in the aorta. Epicardium and sinus venosus generate endothelium of coronary vessels by neovasculo- and angiogenesis, respectively. During a week after ingrowth of vessels from SV and before their ingrowth to the aorta, ventriculo-coronary communications could be found in the heart.

Mechanisms of Myocardial Ischemia in Hypertrophic Cardiomyopathy: Insights From Wave Intensity Analysis and Magnetic Resonance

BackgroundAngina is common in hypertrophic cardiomyopathy (HCM) and is associated with abnormal myocardial perfusion. Wave intensity analysis improves the understanding of the mechanics of myocardial ischemia. ObjectivesWave intensity analysis was used to describe the mechanisms underlying perfusion abnormalities in patients with HCM. MethodsSimultaneous pressure and flow were measured in the proximal left anterior descending artery in 33 patients with HCM and 20 control patients at rest and during hyperemia, allowing calculation of wave intensity. Patients also underwent quantitative first-pass perfusion cardiac magnetic resonance to measure myocardial perfusion reserve. ResultsPatients with HCM had a lower coronary flow reserve than control subjects (1.9 ± 0.8 vs. 2.7 ± 0.9; p = 0.01). Coronary hemodynamics in HCM were characterized by a very large backward compression wave during systole (38 ± 11% vs. 21 ± 6%; p < 0.001) and a proportionately smaller backward expansion wave (27% ± 8% vs. 33 ± 6%; p = 0.006) compared with control subjects. Patients with severe left ventricular outflow tract obstruction had a bisferiens pressure waveform resulting in an additional proximally originating deceleration wave during systole. The proportion of waves acting to accelerate coronary flow increased with hyperemia, and the magnitude of change was proportional to the myocardial perfusion reserve (rho = 0.53; p < 0.01). ConclusionsCoronary flow in patients with HCM is deranged. Distally, compressive deformation of intramyocardial blood vessels during systole results in an abnormally large backward compression wave, whereas proximally, severe left ventricular outflow tract obstruction is associated with an additional deceleration wave. Perfusion abnormalities in HCM are not simply a consequence of supply/demand mismatch or remodeling of the intramyocardial blood vessels; they represent a dynamic interaction with the mechanics of myocardial ischemia that may be amenable to treatment.

PP.LB02.05] THE CORONARY BACKWARD-PROPAGATING ‘SUCTION’ WAVE ARISES FROM A COMBINATION OF MICROCIRCULATORY DECOMPRESSION AND REFLECTION OF A FORWARD-PROPAGATING WAVE ORIGINATING IN THE AORTA

Objective: Coronary wave intensity (WI) analysis has revealed the existence of a large backward-propagating decompression (or ‘suction’) wave (BDW) occurring in early diastole that plays a major role in establishing diastolic coronary blood flow and may have clinical relevance. It has so far been considered that this wave arises entirely due to decompression of intramyocardial vessels during cardiac relaxation, then propagating back towards the aorta. In this study, we investigated whether reflection of the closely preceding forward-propagating decompression wave (FDW), which originates in the aorta, also contributes to the BDW. Design and method: Mechanisms underlying the BDW were elucidated using a previously validated muti-scale computational model of the coronary circulation (Mynard et al, Am J Physiol Heart Circ Physiol, 306 (4):H517-H528, 2014) and left anterior descending (LAD) WI analysis. The model was composed of a lumped parameter heart model, a simple closed loop circulation model, a detailed one-dimensional model of the main conduit coronary arteries and a regionally instantiated multi-layered lumped parameter model of the intramyocardial circulation. After establishing a reference simulation representing an older adult with high blood pressure (155/84 mmHg), all waves arising from the aorta were eliminated by prescribing a reflection coefficient of -1 at the coronary ostia, while maintaining identical intramyocardial conditions as the reference simulation, such that coronary waves could only originate from within the myocardial microvasculature.Results: The LAD WI profile in the reference simulation closely resembled published human data in all respects (Fig. 1). After eliminating waves arising from the aorta, the amplitude of the BDW fell by 69%, indicating that, in the reference case, reflection of the FDW was a major contributor to the BDW. In both simulations, reflection of the BDW at the coronary ostium also produced a forward compression wave (FCW) after the FDW. Conclusions: These virtual experiments suggest that the BDW arises from a combination of 1) active wave generation in the intramyocardial vessels and 2) passive wave reflection of a FDW originating in the aorta. These findings suggest that the conventional interpretation of coronary WI needs to be reconsidered.

OC10_01 Analysis of Small Intramyocardial Vessels of the Heart in Chronic Cocaine Users After Sudden Death

OC10_01 Analysis of Small Intramyocardial Vessels of the Heart in Chronic Cocaine Users After Sudden Death

Prevention of age-induced N(ε)-(carboxymethyl)lysine accumulation in the microvasculature.

N(ε)-(carboxymethyl)lysine (CML) is one of the major advanced glycation end products in both diabetics and nondiabetics. CML depositions in the microvasculature have recently been linked to the aetiology of acute myocardial infarction and cognitive impairment in Alzheimer's disease, possibly related to local enhancement of inflammation and oxidative processes. We hypothesized that CML deposition in the microvasculature of the heart and brain is age-induced and that it could be inhibited by a diet intervention with docosahexaenoic acid (DHA), an omega-3 fatty acid known for its anti-inflammatory and antioxidative actions. ApoE(-/-) mice (n = 50) were fed a Western diet and were sacrificed after 40, 70 and 90 weeks. Part of these mice (n = 20) were fed a Western diet enriched with DHA from 40 weeks on. CML in cardiac and cerebral microvessels was quantified using immunohistochemistry. Cardiac microvascular depositions of CML significantly increased with an immunohistochemical score of 11·85 [5·92-14·60] at 40 weeks, to 33·17 [17·60-47·15] at 70 weeks (P = 0·005). At the same time points, cerebral microvascular CML increased from 6·45; [4·78-7·30] to 12·99; [9·85-20·122] (P = 0·003). DHA decreased CML in the intramyocardial vasculature at both 70 and 90 weeks, significant at 70 weeks [33·17; (17·60-47·15) vs. 14·73; (4·44-28·16) P = 0·037]. No such effects were found in the brain. Accumulation of N(ε)-(carboxymethyl)lysine in the cerebral and cardiac microvasculature is age-induced and is prevented by DHA in the intramyocardial vessels of ApoE(-/-) mice.

Atrial Fibrillation Coincides with the Advanced Glycation End Product Nε-(Carboxymethyl)Lysine in the Atrium

Presence of advanced glycation end products (AGEs) in the heart induces a proinflammatory phenotype. However, the presence of AGEs within atrial tissue of atrial fibrillation (AF) patients is unknown and was analyzed here. Left atrial appendage tissue from 33 AF patients and 9 controls was analyzed for the presence of the major AGEs N(ε)-(carboxymethyl)lysine (CML), VCAM-1, neutrophilic granulocytes, lymphocytes, and macrophages in both the fat tissue and myocardium separately. The total amount of fibrosis was also analyzed. Presence of CML was significantly higher in blood vessels of the left atrial appendage in AF patients as compared to controls, independent of diabetes mellitus. In AF patients, VCAM-1 expression in blood vessels and the numbers of infiltrated neutrophilic granulocytes, lymphocytes, and macrophages significantly increased compared to controls, and were highest in the fat tissue; there was no significant difference in fibrosis compared to controls. Interestingly, total amount of CML and fibrosis in AF and control patients correlated positively. Finally, there was no difference between AF patients based on AF type or surgical indication in the presence of CML, VCAM-1 expression, inflammatory cells, and fibrosis. Our results indicate that in AF the intramyocardial blood vessels of the left atrial appendage have an increased CML presence and proinflammatory status coinciding with a local increase in the number of inflammatory cells.

Evaluation of longitudinal myocardial deformation by 2-dimensional speckle-tracking echocardiography in heart transplant recipients: Relation to coronary allograft vasculopathy

Coronary allograft vasculopathy (CAV) in heart transplant (HTx) recipients is characterized by diffuse affection of epicardial and intramyocardial coronary vessels. Despite significant CAV and anticipated affected myocardial function, left ventricular ejection fraction (LVEF) is often within the normal range, indicating the need of more sophisticated non-invasive methods to detect impaired myocardial function caused by CAV. Global longitudinal strain (GLS) represents a new echocardiographic measurement of systolic myocardial deformation. The aim of the study was to evaluate the relation between GLS measured by 2-dimensional speckle-tracking echocardiography and CAV in HTx patients. The study included 178 HTx patients and 20 healthy, age-matched individuals. All patients had an extensive echocardiographic evaluation and coronary angiography assessing CAV. CAV was classified according to International Society of Heart and Lung Transplantation classification (CAV0-3). CAV was seen in 38.8% of patients. Compared with controls (-20.6% ± 1.4%), GLS was significantly reduced according to the degree of CAV (CAV0, -16.7% ± 2.4%; CAV1, -15.2% ± 2.9%; CAV2-3, -14.0% ± 3.8%; controls, -20.6% ±1.4%; pTREND < 0.0001). In addition, we found decreasing peak systolic mitral annular velocities (pTREND = 0.0040), tissue-tracking values (pTREND = 0.0002), and LVEF according to CAV class (CAV0, 65.3% ± 5.4%; CAV2-3, 56.9% ± 11.7%; pTREND < 0.0001). The HTx population showed significant restrictive physiology compared with the control population, but no significant correlation was seen between CAV class and traditional diastolic parameters such as E/A ratio (pTREND = 0.38) or E-deceleration time (pTREND = 0.14). In contrast to LVEF and conventional pulsed mitral Doppler flow parameters used in the CAV classification, GLS relates to the presence and degree of CAV. The present results suggest GLS as a new method to be included in the monitoring of graft function in relation to CAV.

Apoptosis induction of cardiomyocytes and subsequent fibrosis after irradiation and neoadjuvant chemotherapy

Purpose: Breast cancer treatments can induce important cardiovascular complications. The aim of this study was to evaluate cardiac alterations after irradiation and chemotherapy in an animal model.Material and methods: Wistar rats were divided into three groups: Control, TC+ IR (received chemotherapy and irradiation) and IR (received only irradiation). After 5 months, echocardiography was performed, the animals were euthanized, and the left ventricle was analyzed using light microscopy techniques and Polymerase Chain Reaction (PCR).Results: Echocardiography showed decreases in ejection fraction and cardiac output, in TC+ IR group. Both TC+ IR and IR showed reduced intramyocardial vessel-to-cardiomyocyte ratio, increased connective tissue, cardiomyocyte hypertrophy, increased numbers of apoptotic nuclei and increased Bax/Bcl2 expression. We also observed increased Transforming growth factor (TGF) beta 1 mRNA expression in both groups, but type 1 Procollagen expression was increased in TC+ IR group only.Conclusions: The study suggests that the induced cardiac remodelling begins with the reduction of intramyocardial vessels in the left ventricle tissue. The main consequence is the loss of cardiomyocytes through apoptosis, leading to the replacement of healthy tissue by fibrous tissue. It was observed that the damage caused by the combination of irradiation and chemotherapy induced functional alterations that did not occur when the animals were only irradiated.

Off-pump bilateral internal thoracic artery grafting.

We read with interest the article by Dr. Lytle on bilateral internal thoracic artery (BITA) grafting (1). We congratulate him for an excellent review on the subject. We would like to take this opportunity to humbly express our opinion regarding off-pump use of BITA grafting. Our limited experience contradicts his opinion that off-pump CABG (OPCAB) may have negatively influenced the use of BITA and sequential ITA grafting (1). We have reported a simple technique to use BITA with aortic no touch (2) that can be performed off-pump by surgeons even with limited OPCAB experience. Sequential grafting using LITA-RITA y graft technique off-pump has been in practice for a while. Intra-myocardial blood vessels had been successfully grafted during OPCAB (3). We feel that in the absence of the stress of increasing clamp or bypass time, a perfect anastomosis can be performed even in severely diseased arteries. Moreover, the absence of cardiopulmonary bypass-induced inflammatory response may have a favorable impact on the vulnerability of deep mediastinal infection after BITA use. OPCAB is associated with less use of blood and blood product which is known to reduce immunity. We would argue that immunity may be better preserved after OPCAB because of the absence of inflammatory response and less use of blood and blood product. In addition to routine use of skeletonised ITA, these factors may explain the very low incidence of major infection in our OPCAB patients with BITA grafting. Stroke after CABG is probably the major drawback in all the recent trials comparing CABG with percutanous coronary intervention (PCI). Even with the improvement in technology, it would be difficult to reduce the incidence of stroke to less than 2% after on-pump CABG. Even OPCAB (where aortic side clamp had been used) can be complicated by postoperative incidence of stroke. Stroke after CABG is probably the worst complication. OPCAB with aortic-no-touch can reduce the incidence of stroke to the minimum (4). OPCAB with aortic-no-touch which has the lowest incidence of stroke compares favorably with PCI. We have successfully adopted OPCAB use of BITA grafting in more than 90% of unselected consecutive cases of isolated CABG (5). It is well known that coronary artery disease in the Asian population has a very aggressive pattern affecting the younger generation. Moreover, while PCI is preferred for younger patients with low syntax score, our surgical patients have become more complex with higher syntax scores. By using OPCAB with aortic-no-touch and BITA grafting, we have been able to provide an alternative to PCI which has not only better graft patency rates, and provides complete revascularization but also the incidence stroke is comparable or lower than PCI (even passing coronary angioplasty catheters through diseased aorta can produce stroke). Our limited experience has proved that BITA grafting can be successfully used during OPCAB (5). I congratulate Dr. Lytle for highlighting the superiority of BITA grafting in improving long-term patient outcomes. It will require a change in mindset toward BITA grafting to successfully provide a better alternative to PCI in patients with coronary artery disease.

Abstract 184: Pressure Overload Activates Left Ventricular (LV) Intramyocardial Vascular Endothelial Cells and induces T Cell Infiltration into the LV

Left ventricular dysfunction and Heart Failure (HF) are associated with systemic inflammation with clinical data showing that HF patients have higher levels of circulating pro-inflammatory cytokines. Recruitment of circulating T cells to tissues across the vascular endothelium is a key event in the inflammatory response, but whether it plays a role in the heart in HF is unknown. We hypothesized that pressure overload induced HF activates cardiac endothelial cells resulting in T cell recruitment into the left ventricle (LV). Using transverse aortic constriction (TAC), quantitative flow cytometry, immunohistochemistry, qPCR and real time live cell videomicroscopy, we examined mRNA and protein expression levels of endothelial cell adhesion molecules and the presence of T cell infiltrates in the LV in vivo , and also studied the T cell interactions with primary mouse heart endothelial cells (MHEC) under flow conditions in vitro , comparing Sham and TAC operated mice (6-10/group) during the course of HF. 48h after TAC, in the pre-hypertrophic state, no differences were observed in the recruitment of T cells in the LV. Interestingly, two and four weeks after TAC, when mice developed LVH and LV dysfunction (Fractional Shortening 25±13%), E-Selectin, VCAM-1 and ICAM-1 mRNA levels were significantly upregulated in the LV as compared to Sham mice (2.3, 2.8 and 4 fold, respectively), with notable enhancement of endothelial ICAM-1 protein levels in the LV intramyocardial vessels, and T cells infiltrated in the LV in response to TAC (P≤0.05 TAC vs Sham). Furthermore, T cells isolated from mice 2 and 4 weeks after TAC adhered to MHEC under flow conditions in significantly higher numbers than T cells from Sham mice (P≤0.01 TAC vs Sham). Systemically, the frequency of three different T cell subsets in the peripheral lymphoid organs was increased in TAC vs Sham mice, indicating activation of the adaptive immune response to pressure overload. Taken together, our studies indicate that activation of the heart vascular endothelium occurs in response to pressure overload resulting in T cell recruitment into the LV. Further studies will be needed to determine in the extent to which T cell recruitment into the heart contributes to the pathogenesis of HF.

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<i>Circulation</i> Editors’ Picks

Subepicardial endothelial cells invade the embryonic ventricle wall to form coronary arteries

Coronary arteries bring blood flow to the heart muscle. Understanding the developmental program of the coronary arteries provides insights into the treatment of coronary artery diseases. Multiple sources have been described as contributing to coronary arteries including the proepicardium, sinus venosus (SV), and endocardium. However, the developmental origins of coronary vessels are still under intense study. We have produced a new genetic tool for studying coronary development, an AplnCreER mouse line, which expresses an inducible Cre recombinase specifically in developing coronary vessels. Quantitative analysis of coronary development and timed induction of AplnCreER fate tracing showed that the progenies of subepicardial endothelial cells (ECs) both invade the compact myocardium to form coronary arteries and remain on the surface to produce veins. We found that these subepicardial ECs are the major sources of intramyocardial coronary vessels in the developing heart. In vitro explant assays indicate that the majority of these subepicardial ECs arise from endocardium of the SV and atrium, but not from ventricular endocardium. Clonal analysis of Apln-positive cells indicates that a single subepicardial EC contributes equally to both coronary arteries and veins. Collectively, these data suggested that subepicardial ECs are the major source of intramyocardial coronary arteries in the ventricle wall, and that coronary arteries and veins have a common origin in the developing heart.

Effects of exercise on monocrotaline-induced changes in right heart function and pulmonary artery remodeling in rats

Pulmonary arterial hypertension (PAH) induced by monocrotaline (MCT) is an experimental protocol of right heart failure. We analyzed the role of exercise training on the right ventricle structure and function, pulmonary artery remodeling, and GSK-3β expression. Rats were divided among the following groups: sedentary control (SC), sedentary monocrotaline (SM), trained control (TC), and trained monocrotaline (TM). Rats underwent exercise training for a period of 5 weeks, with 3 weeks post-MCT injection. Rats in the SM and TM groups presented with an increase in right ventricle hypertrophy indexes and lung congestion. The right ventricular end diastolic pressure (RVEDP), right ventricular systolic pressure (RVSP), and its minimum and maximal pressure derivates were increased in the SM and TM groups. The right ventricle interstitial volume pulmonary artery thickness and p-GSK-3β/GSK-3β were increased in the MCT groups as compared with the control groups. The TM group had a reduction in interstitial volume, p-GSK-3β/GSK-3β ratio, pulmonary artery thickness, RVEDP, and an increase in intramyocardial vessels volume as compared with the SM group. The overall results have shown that the exercise protocol used promoted positive changes in right ventricle and pulmonary artery remodeling. These observations also suggest that structural remodeling may be influenced by signaling proteins, such as GSK-3β.

Effects of high-fat chow on heart tissue in acute and chronic experimental murine schistosomiasis mansoni

This study aimed to investigate myocardial injuries in mice infected with Schistosoma mansoni and fed a high-fat chow. Sections of myocardial tissue from S. mansoni-infected mice, and controls that had been killed 9 and 17 weeks post-infection, were stained with H&E and Picrosirius red. Histopathological examination, stereological design-based method (optical disector) and morphometry (vessels, cardiomyocytes and an amount of collagen) were used. Data were analysed using two-way ANOVA. Regardless of time of infection, myocardial tissue from the infected mice fed high-fat chow showed myocarditis characterized by a higher number of inflammatory foci, several areas displaying coagulation of cardiac fibres, a greater loss of cardiomyocytes and fibroblast proliferation than in the standard chow control. Comparing infected mice from acute and chronic infections, a higher cardiomyocyte hyperplasia (P < 0·0001) and higher amounts of collagen (P < 0·05) were observed than in standard chow control. In addition, all animals fed high-fat chow showed lower numerical density and total number of cardiomyocytes (P < 0·05), thicker vessel walls and narrowed luminal intramyocardial vessels (P > 0·05) than in the standard chow control. Altogether the data supported the view that a double burden has a synergistic deleterious effect on the myocardial tissue.

Cardiac Micro–Computed Tomography Imaging of the Aging Coronary Vasculature

Alterations at the level of the coronary circulation with aging may play an important role in the evolution of age-associated changes in left ventricular (LV) fibrosis and function. However these age-associated changes in the coronary vasculature remain poorly defined primarily due to the lack of high resolution imaging technologies. The current study was designed to utilize cardiac micro-computed tomography (micro-CT) technology as a novel imaging strategy, to define the 3-dimensional coronary circulation in the young and aged heart and its relationship to LV fibrosis and function. Young (2 months old; n=10) and aged (20 months old; n=10) Fischer rats underwent cardiac micro-CT imaging as well as echocardiography, blood pressure, and fibrosis analysis. Importantly, when indexed to LV mass, which increased with age, the total and intramyocardial vessel volumes were lower, whereas the epicardial vessel volume, with and without indexing to LV mass, was significantly higher in the aged hearts compared with the young hearts. Moreover, the aged hearts had a significantly lower percentage of intramyocardial vessel volume and a significantly higher percentage of epicardial vessel volume, when normalized to the total vessel volume, compared with the young hearts. Further, the aged hearts had significant LV fibrosis and mild LV dysfunction compared with the young hearts. This micro-CT imaging study reports the reduction in normalized intramyocardial vessel volume within the aged heart, in association with increased epicardial vessel volume, in the setting of increased LV fibrosis, and mild LV dysfunction.

NOX5 Expression Is Increased in Intramyocardial Blood Vessels and Cardiomyocytes after Acute Myocardial Infarction in Humans

Reactive oxygen species producing NADPH oxidases play important roles under different (patho)physiological conditions. NOX1, NOX2, and NOX4 are important sources of reactive oxygen species in the heart, but knowledge of the calcium-dependent NOX5 in the heart is lacking. The presence of NOX5 was studied via RT-PCR in heart tissue from patients with end-stage heart failure; the tissue was obtained during cardiac transplantation surgery. NOX5 positivity and cellular localization were studied via IHC and digital-imaging microscopy in heart tissues of patients who did not have heart disease and in infarction areas of patients who died of myocardial infarctions of different durations. Furthermore, NOX5 expression was analyzed in vitro by using Western blot analysis. NOX5 RNA was found in the hearts of controls and patients with ischemic cardiomyopathy. In controls, NOX5 localized to the endothelium of a limited number of intramyocardial blood vessels and to a limited number of scattered cardiomyocytes. In infarcted hearts, NOX5 expression increased, especially in infarctions >12 hours, which manifested as an increase in NOX5-positive intramyocardial blood vessels, as well as in endothelium, smooth muscle, and cardiomyocytes. NOX5 was found in cardiomyocyte cytoplasm, plasma membrane, intercalated disks, and cross striations. Western blot analysis confirmed NOX5 expression in isolated human cardiomyocytes. For the first time to our knowledge, we demonstrate NOX5 expression in human intramyocardial blood vessels and cardiomyocytes, with significant increases in the affected myocardium after acute myocardial infarction.

Nitric Oxide Synthase in Heart and Thoracic Aorta After Liver Ischemia and Reperfusion Injury: An Experimental Study in Rats

We tested the effects of liver reperfusion in the immunohistochemical expression of nitric oxide synthase on the thoracic aorta and the heart. We randomized 24 male Wistar rats into 3 groups: (1) control; (2) R2 group, with 60 minutes of partial (70%) liver ischemia and 2 hours of global liver reperfusion; (3) and R6 group, with 60 minutes of partial liver ischemia and 6 hours of global liver reperfusion. In the heart, there was little, diffuse immunohistochemical endothelial staining; immunohistochemical inducible nitric oxide synthase staining was expressed in the adventitia layer of intramyocardial vessels in both cases, with a time-dependent but not statistically significant increase. In the thoracic aorta, a time-dependent decrease in endothelial nitric oxide synthase expression in the muscular layer after reperfusion, which was statistically significant in R6 versus the control. Positive immunostaining for inducible nitric oxide synthase was seen in the muscular and endothelial layers, and this varied from moderate in the control group, to light in the endothelium in groups R2 and R6. We observed changes that may be implicated in heart injury and impairment of aortal tone after liver ischemia and reperfusion injury.

Hyaluronan and Collagen in Human Hypertrophic Cardiomyopathy: A Morphological Analysis

Introduction. The hypertrophic cardiomyopathy (HCM) disease process is not only limited to cardiomyocyte abnormalities but also engages the extracellular matrix. Hyaluronan (HA) and its receptor CD44 are involved in cellular growth and tissue proliferation but have so far been less studied in myocardial hypertrophy. In HCM, collagens are abundant but their histological distribution and relation to hyaluronan have not been described. Material and Methods. Myocardial specimens from 5 patients with symptomatic left ventricular tract obstruction undergoing myectomy due to HCM were processed for histochemistry and immunohistochemistry. Results. HA staining was more intense in HCM patients. The histological distribution of HA was the same in patients and controls, that is, interstitial staining including the space between cardiomyocytes, in fibrous septa, and in the adventitia of intramyocardial blood vessels. CD44 was not detected in the myocardium of patients or controls. Collagen I showed the same general localisation as HA but detailed distribution differed. Conclusions. This is the first study that describes the distribution of hyaluronan in human HCM. HA staining is more intense in HCM patients but without coexpression of its receptor CD44, at least not in the chronic phase of HCM. HA and collagen I have the same localisation.

Early Cardiac Allograft Vasculopathy: Are the Viruses to Blame?

This paper describes a case of early (7 months after transplant) cardiac allograft vasculopathy. This-43-year-old (CMV positive, EBV negative) female patient underwent an orthotopic heart transplant with a (CMV negative, EBV positive) donor heart. She had a history of herpes zoster infection and postherpetic neuralgia in the past. The patient's panel reactive antibodies had been almost undetectable on routine surveillance testing, and her surveillance endomyocardial biopsies apart from a few episodes of mild-to-moderate acute cellular rejection (treated adequately with steroids) never showed any evidence of humoral rejection. The postoperative course was complicated by multiple admissions for upper respiratory symptoms, and the patient tested positive for entero, rhino, and coronaviruses serologies. During her last admission (seven months postoperatively) the patient developed mild left ventricular dysfunction with an ejection fraction of 40%. The patient's endomyocardial biopsy done at that time revealed concentric intimal proliferation and inflammation resulting in near-total luminal occlusion in the epicardial and the intramyocardial coronary vessels, suggestive of graft vasculopathy with no evidence of rejection, and the patient had a fatal ventricular arrhythmia.