Cardiac Muscle Necrosis Research Articles

Real-Time Autophagic Flux Measurements in Live Cells Using a Novel Fluorescent Marker DAPRed.

Autophagy is a conserved homeostatic mechanism involved in cellular homeostasis and many disease processes. Although it was first described in yeast cells undergoing starvation, we have learned over the years that autophagy gets activated in many stress conditions and during development and aging in mammalian cells. Understanding the fundamental mechanisms underlying autophagy effects can bring us closer to better insights into the pathogenesis of many disease conditions (e.g., cardiac muscle necrosis, Alzheimer's disease, and chronic lung injury). Due to the complex and dynamic nature of the autophagic processes, many different techniques (e.g., western blotting, fluorescent labeling, and genetic modifications of key autophagy proteins) have been developed to delineate autophagy effects. Although these methods are valid, they are not well suited for the assessment of time-dependent autophagy kinetics. Here, we describe a novel approach: the use of DAPRed for autophagic flux measurement via live cell imaging, utilizing A549 cells, that can visualize and quantify autophagic flux in real time in single live cells. This approach is relatively straightforward in comparison to other experimental procedures and should be applicable to any in vitro cell/tissue models. Key features • Allows real-time qualitative imaging of autophagic flux at single-cell level. • Primary cells and cell lines can also be utilized with this technique. • Use of confocal microscopy allows visualization of autophagy without disturbing cellular functions.

ВЛИЯНИЕ ТРЕВОЖНО-ДЕПРЕССИВНЫХ РАССТРОЙСТВ НА РАЗВИТИЕ ИНФАРКТА МИОКАРДА

The article discusses the relationship between depressive disorders and ischemia, as well as changes in the blood coagulation system in patients with depressive disorders. Significant defects in the physiological characteristics of platelets are revealed, including increased reactivity and increased production of platelet factor 4 and p-thromboglobulin. The features of increased vasoconstriction, platelet activation, and thrombus formation are also considered, which may be the basis for the progression of coronary artery disease and mortality after acute myocardial infarction in patients with depression. Aim. To reveal the impact of anxiety-depressive disorders on the development of cardiac muscle necrosis. Materials and methods. Experimental and clinical studies have been carried out on patients with necrosis of the heart muscle. Results. Patients with necrosis of the heart muscle and depression do not immediately seek medical help, unlike patients without depression. This may affect treatment options (e.g., thrombolysis) and the prognosis in such patients. Conclusion. Further research is needed to determine whether depression causes inflammation, inflammation causes depression, or if a third, as-yet-unknown pathological process causes both inflammation and depression.

The Effects of Bacterial Lipopolysaccharide (LPS) on Turkey Poults: Assessment of Biochemical Parameters and Histopathological Changes.

A lipopolysaccharide (LPS) is a large molecule and an outer membrane glycolipid found in Gram-negative bacteria, including Escherichia coli (E. coli). These molecules (LPS) target acute inflammatory responses and significant physiological changes. Importantly, E. coli is considered one of the most important bacterial causes of avian colibacillosis that affect domestic turkey industry. However, little information is available about the potential influence of LPS on the biochemical parameters and histopathological changes in turkey poults. Therefore, this study aimed to evaluate the influence of bacterial lipopolysaccharide (LPS) molecules on serum biomarkers and histopathological changes in turkey poults. The birds were randomly divided into five groups, as follows: group I did not receive any inoculation; group II was inoculated with sterile saline; and groups III, IV, and V were inoculated intraperitoneally with LPS at 0.01, 0.1, and 1 mg/kg of body weight (BW), respectively. The biochemical parameters and the histopathology of different organs were examined in all birds one day post-inoculation. Our results revealed hypolipidemia, hypoglycemia, a significant decrease in uric acid, and a significant increase in serum activities of aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), and creatine kinase (CK), as well as cardiac troponin T concentrations in treated groups. Moreover, there was a significant increase in α1-, β-, and γ-globulin concentrations and a decrease in albumin and α2-globulin concentrations in group V. However, a significant increase in α2- and γ-globulin levels and a decrease in albumin levels were detected in groups III and IV. In addition, significant decreases in the albumin/globulin ratio were recorded in all LPS-treated groups. Hepatocellular and cardiac muscle necrosis, slight renal changes, and massive pulmonary inflammatory reactions were recorded. This study provides valuable information about serum biomarkers, protein fractions, and histopathological changes in turkey poults treated with LPS for further investigations of pathophysiological mechanisms in avian medicine along with biomedical research.

Abstract 10279: Altered Myocardial Gene Expression in H2-kbm1 Mice with Orexinergic Dysfunction and Heart Failure

Introduction: Mice carrying a homozygous frameshift mutation of the class I major histocompatibility antigen H2-K1 (H2-Kbm1) exhibit impaired development of hypothalamic orexinergic neurons. Similar to mice lacking the hypocretin (orexin) 2 receptor, H2-Kbm1 mice develop dilated cardiomyopathy and systolic heart failure (HF) from an early age. Previous studies suggest response to orexinergic signaling is predictive of patient response to current HF pharmacotherapeutic regimes. Our goal was to characterize the myocardial gene expression profiles of H2-Kbm1 mice. Methods: RNA was isolated from mice hearts (wild type n=5, mutant n=7) via the Qiagen RNeasy Mini Kit. DNase treatment was done to limit contamination of genomic DNA. Gene expression was measured using Illumina nexteq500 and 550 sequencing systems from a DNA library generated via the NuGene library kit (10 ng RNA). RNA-seq data analyses including comparisons, volcano and heatmap plots were completed. Results: H2-Kbm1 mice differentially express 398 myocardial genes compared to control mice. Ingenuity pathway analysis indicates that these genes are involved in necrosis of cardiac muscle (z-score -1.8), cell death (z-score 1.6), and cardiac contractility (z-score -4). Upstream signaling analysis suggest regulation by Mir-122 (z-score 2.4), DNMT3 A and B (z-score 3.3 and 2.5), VEGF (z-score 4.6) and rosiglitazone (z-score -6.8). Canonical pathway analysis is shown in Figure 1. Conclusion: H2-Kbm1 mice develop heart failure with marked myocardial transcriptional abnormalities that lead to impaired cardiac contraction and cell death. Differentially expressed genes are predominantly involved in mitochondrial function, oxidative phosphorylation, sirtuin signaling and the TCA cycle. Regulation of these genes is associated with miR-122, DNA methylations by DNMT3 A & B, VEGF and rosiglitazone signaling. The orexin pathway is a potential target for heart failure therapeutics.

Natural Infection of Covert Mortality Nodavirus in Small Yellow Croaker in Coastal Water

Covert mortality nodavirus (CMNV) is an alphanodavirus mainly infecting marine shrimp and co-inhabiting organisms in aquaculture ponds. To evaluate the possibility of CMNV prevalence in the wild fish species, epidemiological survey of CMNV infection in Larimichthys polyactis, the dominant species in the Yellow Sea and East China Sea, were conducted in the present study. We performed CMNV RT-LAMP assay in samples of L. polyactis collected in August 2018 and 2019 and found that CMNV prevalence was 18% and 7%, respectively. The nucleotide sequences of both RdRp and capsid protein genes of CMNV from L. polyactis were 99% similar to those of CMNV isolated from shrimp. CMNV-positive L. polyactis exhibited necrosis of cardiac muscle, oocytes loosely arranging, severe cytoplasmic vacuolation of hepatocytes, moderate pyknosis of brain pyramidal cells, degenerate renal tubular cells with ill-defined margins, and declined spleen cells in the histological examination. Moreover, CMNV-positive signals were further observed in pyramidal cells of the brain, the cortical area of the kidney, oocyte growth rings, and in necrotic tissues of cardiac muscle, liver, and spleen in the in situ hybridization assay. The results revealed that CMNV had colonized in the wild populations of L. polyactis and the ecological risk of CMNV spread and epidemic in wild fish in the coastal water was non-negligible.

Abstract 14981: Altered Gene Expression in Diabetic Heart Failure Patients

Introduction: Diabetes and heart failure are very closely associated. Diabetes patients have an increased risk of developing heart failure and heart failure patients are at higher risk of developing diabetes. Changes occur in myocardial glucose metabolism in end stage heart failure patients and newer therapies for diabetes such as SGLTi improve heart failure outcomes. Our objective was to identify transcriptional changes associated with diabetes in heart failure patients. Methods: Transcriptional profiles were compared in heart tissues obtained at the time of LVAD implant among diabetic heart failure (HF) (n=16), non-diabetic (n=10) HF patients and control (n=3) non failing hearts. RNASeq analysis utilized a custom-targeted panel for 140 genes on the Ion Torrent Personal Genome Machine. Coverage analysis as well as mapping the reads and alignment was done using the Ion Torrent Browser SuiteTM. The Bejamini-Hochberg method was used to control the false discovery rate to be no more than 0.05. Ingenuity Pathway Analysis (IPA) was also performed to understand the biological pathways involved. Results: Our sample population was 82% male with an average age of 51 and 84% Caucasian, 14% African American and 2% Asian. Average ejection fraction was quite low <25% and average NYHA was 3.5 in the HF populations. Expressions of contractile muscle and ion channels proteins decreased significantly between HF patients and control. Increased expression of chemokine ligand 4 (CCL4), chemokine ligand 2 (CCL2) and collagen type 1 alpha1 (COL1A1) were observed in diabetic HF compared to non-diabetic HF patients. IPA analysis with log fold change between HF and control revealed activation of both methylation genes DNMT3A and B, necrosis of cardiac muscle and death of cardiomyocytes with 2.0 Z score. Conclusions: Diabetic heart failure patients have increased expression of chemokines and extracellular matrix genes, which may contribute to disease progression. Up regulation of CCL4 and CCL2 in diabetic HF patients may cause additional risk of heart diseases through inflammatory pathways and increased expression of collagen may contribute to myocardial fibrosis. Down regulation of contractile proteins, and ion channels were similar in diabetic and non-diabetic HF patients.

Revisiting the Effects of Different Dietary Sources of Selenium on the Health and Performance of Dairy Animals: a Review.

Selenium (Se) is one of the most important essential trace elements in livestock production. It is a structural component in at least 25 selenoproteins such as the iodothyronine deiodinases and thioredoxin reductases as selenocysteine at critical positions in the active sites of these enzymes. It is also involved in the synthesis of the thyroid hormone and influences overall body metabolism. Selenium being a component of the glutathione peroxidase enzyme also plays a key role in the antioxidant defense system of animals. Dietary requirements of Se in dairy animals depend on physiological status, endogenous Se content, Se source, and route of administration. Most of the dietary Se is absorbed through the duodenum in ruminants and also some portion through the rumen wall. Inorganic Se salts such as Na-selenate and Na-selenite have shown lower bioavailability than organic and nano-Se. Selenium deficiency has been associated with reproductive disorders such as retained placenta, abortion, early embryonic death, and infertility, together with muscular diseases (like white muscle disease and skeletal and cardiac muscle necrosis). The deficiency of Se can also affect the udder health particularly favoring clinical and subclinical mastitis, along with an increase of milk somatic cell counts in dairy animals. However, excessive Se supplementation (5 to 8 mg/kg DM) can lead to acute toxicity including chronic and acute selenosis. Se is the most vital trace element for the optimum performance of dairy animals. This review focuses to provide insights into the comparative efficacy of different forms of dietary Se (inorganic, organic, and nano-Se) on the health and production of dairy animals and milk Se content.

ИНФАРКТОПОДОБНЫЕ СОСТОЯНИЯ В КЛИНИЧЕСКОЙ ПРАКТИКЕ ВРАЧА-КАРДИОЛОГА

Зачастую постановка диагноза «острый инфаркт миокарда» не представляет особых трудностей. Наличие характерной клинической картины, соответствующих изменений на электрокардиограмме и изменений профиля тропонинов позволяет говорить о вероятном ишемическом повреждении и развитии некроза сердечной мышцы. Однако существуют патологические состояния, которые схожи с инфарктом миокарда по всем диагностическим критериям и тем самым затрудняют диагностику самого инфаркта. В данной обзорной статье описаны инфарктоподобные состояния, с которыми наиболее часто приходится проводить дифференциальную диагностику. В статье уделено внимание ключевым признакам, а также основным методам диагностики, позволяющим своевременно дифференцировать истинный инфаркт миокарда и такое инфарктоподобное состояние, что в свою очередь позволит значительно снизить смертность и возникновение осложнений от данной патологии.

THE DIAGNOSTIC VALUE OF TROPONIN I TESTING TO CORONARY ANGIOGRAPHY WITH A POINT OF CARE TESTING INSTRUMENT IN PATIENTS WITH ACUTE MYOCARDIAL INFARCTION

Myocardial infarction consists of STEMI and NSTEMI. Acute myocardial infarction is diagnosed by WHO criteria when at least two of the following three criteria are met: chest pain, electrocardiography (ECG) result changes, and biomarker. Troponin I is specific for cardiac muscle and has an increased level even in small cardiac muscle necrosis and not affected by the renal failure and muscle trauma but have not been standardized by WHO. This research aimed to find the effectivity of Troponin I examination with POCT to help the diagnosis and early detection of AMI. Thus each product has varied sensitivity and specificity. A cross-sectional study was conducted in the Clinical Pathology Laboratory and Cardiac Center of the Dr. Wahidin Sudirohusodo Hospital Makassar using suspected AMI patients as the subject. Troponin I level tested by POCT from August 2015 to July 2016. Data were analyzed statistically using the ROC curve with SPSS software. A total of 88 patients suspected with AMI, aged 36 to 75 years old. From the tested cut-off values (0.02, 0.03, 0.04, 0.5, 0.06, 0.07, 0.08 μg/L) the best cut-off value was 0.03 μg/L (93.9% sensitivity, 95.5% specificity, PPV 98.4%, NPV 84.0%, and 94.3% accuracy) where the cut-off value of 0.03 μg/L was the value recommended by the toolkit manual. Even if the cut-off value of 0.02 or 0.04 was used, the sensitivity and specificity value was still fairly good. Troponin I testing using POCT with a cut-off value of 0.03 μg/L can be used routinely in supporting the AMI diagnosis because it is a rapid test with a portable instrument and excellent diagnostic value.

Infection of covert mortality nodavirus in Japanese flounder reveals host jump of the emerging alphanodavirus.

Interspecies transmission of viruses, where a pathogen crosses species barriers and jumps from its original host into a novel species, has been receiving increasing attention. Viral covert mortality disease, caused by covert mortality nodavirus (CMNV), is an emerging disease that has recently had a substantial impact on shrimp aquaculture in Southeast Asia and Latin America. While investigating the host range of CMNV, we found that this virus is also capable of infecting populations of the farmed Japanese flounder Paralichthys olivaceus, a vertebrate host. The infected fish were being raised in aquaculture facilities that were also producing marine shrimp. Through RT-nPCR, targeting the RNA-dependent RNA polymerase (RdRp) gene of CMNV, we found that 29 % of the fish sampled were positive. The amplicons were sequenced and aligned to the RdRp gene of shrimp CMNV and were found to have 98 % identity. Histopathological examination indicated that CMNV-positive fish showed vacuolation of nervous tissue in the eye and brain, as well as extensive necrosis of cardiac muscle. In situ hybridization showed positive reactions in tissues of the eye, brain, heart, liver, spleen and kidney of infected fish. Transmission electron microscopy showed the presence of CMNV-like particles in all of the above-mentioned tissues, except for brain. The novel finding of a shrimp alphanodavirus that can also infect farmed P. olivaceus indicates that this virus is capable of naturally crossing the species barrier and infecting another vertebrate. This finding will contribute to the development of efficient strategies for disease management in aquaculture.

Confocal Laser Scanning Microscope, Raman Microscopy and Western Blotting to Evaluate Inflammatory Response after Myocardial Infarction

Cardiac muscle necrosis is associated with inflammatory cascade that clears the infarct from dead cells and matrix debris, and then replaces the damaged tissue with scar, through three overlapping phases: the inflammatory phase, the proliferative phase and the maturation phase. Western blotting, laser confocal microscopy, Raman microscopy are valuable tools for studying the inflammatory response following myocardial infarction both humoral and cellular phase, allowing the identification and semiquantitative analysis of proteins produced during the inflammatory cascade activation and the topographical distribution and expression of proteins and cells involved in myocardial inflammation. Confocal laser scanning microscopy (CLSM) is a relatively new technique for microscopic imaging, that allows greater resolution, optical sectioning of the sample and three-dimensional reconstruction of the same sample. Western blotting used to detect the presence of a specific protein with antibody-antigen interaction in the midst of a complex protein mixture extracted from cells, produced semi-quantitative data quite easy to interpret. Confocal Raman microscopy combines the three-dimensional optical resolution of confocal microscopy and the sensitivity to molecular vibrations, which characterizes Raman spectroscopy. The combined use of western blotting and confocal microscope allows detecting the presence of proteins in the sample and trying to observe the exact location within the tissue, or the topographical distribution of the same. Once demonstrated the presence of proteins (cytokines, chemokines, etc.) is important to know the topographical distribution, obtaining in this way additional information regarding the extension of the inflammatory process in function of the time stayed from the time of myocardial infarction. These methods may be useful to study and define the expression of a wide range of inflammatory mediators at several different timepoints providing a more detailed analysis of the time course of the infarct.

Clenbuterol toxicosis in three Quarter Horse racehorses after administration of a compounded product

3 Quarter Horse racehorses were examined for suspected clenbuterol overdose 12 to 24 hours after administration by mouth of a compounded clenbuterol product. All horses developed sinus tachycardia, muscle tremors, hyperhidrosis, and colic. Abnormalities on serum biochemical analysis included hyperglycemia, azotemia, and high creatine kinase activity. The presence of clenbuterol in the serum of all 3 horses and in the product administered was confirmed and quantified by use of liquid chromatography-electrospray tandem mass spectrometry. Propranolol (0.01 mg/kg [0.005 mg/lb], IV) was administered to all 3 horses for antagonism of β-adrenergic effects and caused a transient decrease in heart rate in all patients. All horses also received crystalloid fluids IV and other supportive treatment measures. Two horses were euthanatized (2 and 4 days after admission) because of complications. One horse recovered and was discharged 4 days after admission to the hospital. In the 2 nonsurviving horses, skeletal and cardiac muscle necrosis was evident at necropsy, and tissue clenbuterol concentrations were highest in the liver. Clenbuterol is a β(2)-adrenergic receptor agonist licensed for veterinary use as a bronchodilator. At doses ≥ 10² μg/kg (4.5 μg/lb), in excess of those normally prescribed, β-adrenergic stimulation by clenbuterol may cause sustained tachycardia, muscle tremors, hyperglycemia, and cardiac and skeletal muscle necrosis. Laminitis, acute renal failure, rhabdomyolysis, and cardiomyopathy were fatal complications associated with clenbuterol overdose in 2 horses in the present report. At the dose administered, propranolol was effective for short-term control of sinus tachycardia, but it did not alleviate all clinical signs in patients in the present report. These cases demonstrated the risks associated with the use of nonprescribed compounded medications for which the ingredients may be unknown.

Limited Myocardial Muscle Necrosis Model Allowing for Evaluation of Angiogenic Treatment Modalities

The currently accepted model for creating infarcted cardiac tissue in a rat model involves ligation of the left anterior descending artery (LAD), either proximally or at the bifurcation level. This procedure requires significant technical expertise and, even in skilled hands, commonly results in a 30% to 60% animal mortality. The authors propose a new model for creating a limited area of myocardial muscle necrosis that can be effectively studied. It involves a distal electrocautery occlusion of the LAD terminal branches and coagulation of the surrounding muscle. The model is consistently reproducible and decreases the morbidity of the study animals. It provides a cardiac muscle necrosis model not dependent on survival, while allowing study of the post injured state of the muscle and surrounding scar. This allows researchers to evaluate neovascularization and healing of the scar and peri-necrotic muscle, to assess improving blood flow with treatment by techniques designed to improve and stimulate angiogenesis, and to measure the outcome of stem-cell transplants for potential clinical use.

Establishment of a porcine model of patent foramen ovale

Objective: To investigate the feasibility of developing an animal model of patent foramen ovale (PFO) in piglets by percutaneous atrial septal puncture and balloon dilation.Methods: A standardized percutaneous atrial trans-septal puncture and balloon dilation was conducted in 11 healthy piglets under general anesthesia. A Rups-100 system inserted through a femoral vein was used for the transseptal puncture, and subsequent balloon dilatation was performed at the puncture site to imitate a PFO. Euthanasia and autopsy were performed on day 1 in one piglet (early autopsy), and on day 21 in the remaining ten piglets (late autopsy).Results: Artificial PFO was successfully created in all piglets and verified by fluoroscopy. No major technical difficulty or complication was encountered except in one which developed mild hemopericardium. In the piglet that had early autopsy, the artificial foramen was measured 0.8 × 0.7 cm2 in cross-section and aggregates of erythrocytes were revealed over its rim under light microscopy. In the late autopsy group (n=10), seven piglets had the created foramens healed and sealed off, while the other three showed relatively small residual lumens measured 0.1 × 0.2 cm2, 0.2 × 0.2 cm2 and 0.1 × 0.3 cm2 in cross-section, respectively. Histological examination of specimens from the late autopsy group showed variable neointima hyperplasia, cardiac muscle necrosis and focal fibrosis at the puncture site, regardless of the course of healing.Conclusion: Artificial creation of PFO in piglets is feasible by percutaneous atrial septal puncture and balloon dilation. This protocol may serve as a research model for PFO-related stroke in human.

Regenerating More Than Muscle in Muscular Dystrophy

Duchenne muscular dystrophy (DMD) is a progressive muscle-wasting disorder of skeletal and cardiac muscle. Mutations in the dystrophin gene produce DMD, but much is still unknown about the pathophysiology of DMD. Dystrophic muscle is defined by replacement of normal myofibers by connective tissue and adipocytes. Normal skeletal muscle is highly regenerative and, in the face of continued degeneration, muscle regeneration in DMD is robust, although insufficient to match the pace of degeneration. The dystrophin protein is a subsarcolemmal, spectrin repeat–containing protein of skeletal muscle myofibers and cardiomyocytes. Dystrophin associates tightly with a constellation of transmembrane proteins forming the dystrophin-glycoprotein complex (DGC). Extracellularly, the DGC binds to laminin 2, and intracellularly, the DGC binds to cytoplasmic γ-actin, a myocyte-specific form of filamin and neuronal nitric oxide synthase (nNOS). Positioned at the plasma membrane, the DGC is a mechanosignaling complex that connects the extracellular matrix with the cytoskeleton, and dystrophin is central to this role.1 When dystrophin is absent, as is the case in DMD, the entire DGC is destabilized. The dissolution of the DGC produces plasma membrane instability associated with increased intracellular calcium and myofiber degeneration. See p 3341 The ongoing and widespread muscle degeneration in DMD produces a number of systemic responses. In the present issue of Circulation , Straino and colleagues2 now show that arteriogenesis is enhanced in mdx mice, a mouse model of DMD. Under ischemic conditions, an increase in hindlimb perfusion was seen in mdx as compared with control mice. As an explanation of increased perfusion, muscle from mdx mice was found to have longer arterioles compared with control muscle. Interestingly, capillary density was not increased, and the observed difference in blood flow was attributed solely to arteriole length differences consistent with enhanced arteriogenesis. Given the prominent regeneration that is a feature of mdx muscle, …

Experimental Tribulus terrestris poisoning in sheep: clinical, laboratory and pathological findings.

Eleven native sheep, 1-2 years old, of both sexes were randomly divided into two groups, 6 sheep being allocated to the experimental group and 5 serving as controls. The sheep in the experimental group were fed 80% Tribulus terrestris and 20% alfalfa hay and wheat straw, while the control sheep were given a mixture of 40% alfalfa hay and 60% wheat straw. Clinical signs of hepatogenous photosensitivity were observed from day 11, including reddening and crust formation on the muzzle, nose, ears and eyelids, depression, weight loss, icterus, conjunctivitis, and yellow discoloration of the urine. Laboratory findings on weekly samples indicated significant differences (p < 0.05) in white blood cell count, total plasma protein and fibrinogen, total and direct bilirubin, blood urea nitrogen and creatinine concentrations, and aspartate aminotransferase and alkaline phosphatase activities. There were no significant differences in the packed cell volume, in the neutrophil, lymphocyte or eosinophil counts, or in the serum calcium, phosphorus, potassium, sodium or chloride concentrations. At necropsy of the experimental animals, there were various degrees of generalized icterus and the livers were swollen and discolored by bile pigment. Histopathological examination revealed varying amounts of crystalloid material in the bile ducts and renal tubules, hepatocellular degeneration, biliary fibrosis and proliferation, renal tubular necrosis and focal necrosis of cardiac muscle.

Ganciclovir and cidofovir treatment of cytomegalovirus-induced myocarditis in mice.

The cardiovascular disease myocarditis is characterized by inflammation and necrosis of cardiac muscle. This disease has been associated with various viral etiologies, including cytomegalovirus (CMV). Murine CMV (MCMV) infection of adult BALB/c mice produces a disease with acute and chronic phases similar to that found in humans. In our murine model, we have investigated the therapeutic efficacy of antiviral drug administration on myocarditis. Two drugs commonly used for CMV treatment, ganciclovir and cidofovir, were subjected to trials, with both drugs showing potent antiviral activity against MCMV both in vitro and in vivo. The acute phase of myocarditis was significantly reduced when antiviral therapy commenced 24 h postinfection. Such treatment also reduced the severity of the chronic phase of myocarditis. In contrast, antiviral treatment commencing after the acute phase had no effect on chronic myocarditis. Reinfection of mice with MCMV caused exacerbation of myocardial inflammation. Such an increase in severity of myocarditis could be prevented with either ganciclovir or cidofovir treatment, but the preexisting inflammation and necrosis of the myocardium persisted. These data highlight possible therapeutic uses of antiviral drugs in viral myocarditis as well as further elucidating the pathogenic nature of the disease.

Evaluation of Stratus CS stat fluorimetric analyser for measurement of cardiac markers Troponin I (cTnI), creatine kinase MB (CK-MB), and myoglobin.

Myoglobin, CK-MB, and Troponin I (cTnI) are cardiac muscle necrosis markers that are useful for detecting acute myocardial infarction (AMI). The Stratus CS (Dade Behring, Inc.) is a discrete fluorimetric immunoassay analyser designed for the determination of the three cardiac markers from a single sample of whole blood or plasma. Overall analytical performances of the Stratus CS provided by Dade Behring were evaluated according to the French Society of Clinical Biology guidelines. Within-run imprecision (n = 20) for the three parameters at three levels gave values under 5%, whereas CVs for between-run imprecision (n = 20) were under 6%. The sensitivities were 0.03 microg/L for cTnI and 0.4 microg/L for CK-MB. Linearities extended from 0-50 microg/L for cTnI, 0-140 microg/L for CK-MB, and 1-900 microg/L for myoglobin. The results, particularly those obtained on whole-blood samples, correlated well with those obtained on Stratus II. We did not find any interference with haemolysis, icterus, or lipemia. The system was very easy to use, and fulfills the requirements for the analysis of the three cardiac markers in patients with acute chest pain in emergency situations.

Muscular dystrophy.

Muscular dystrophy.

Clinical features of blister beetle poisoning in equids: 70 cases (1983–1996)

Objective To document clinical signs and gross pathologic changes associated with naturally acquired cantharidiasis (blister beetle poisoning) in equids. Design Retrospective study. Animals 70 equids with laboratory-confirmed blister beetle poisoning. Procedure Medical records were reviewed to obtain history, physical examination findings, feeding practices, and diagnostic test and necropsy results. Results 32 horses and 2 donkeys died from exposure to cantharidin, whereas 36 horses survived. Diet content varied, but alfalfa hay was the common component. Onset of signs of disease was rapid. Most equids had signs of gastrointestinal tract distress. Six horses had nonspecific neurologic signs. All equids dying from cantharidiasis were in shock terminally, with duration of clinical signs ranging from 3 to 18 hours. Six horses that died had no gross lesions, whereas 14 had mild to moderate erythema of gastric, small intestinal, or colonic mucosa. Only 2 horses had gastric or duodenal ulceration, and 2 had hemorrhage of the urinary bladder mucosa. One horse had cardiac muscle necrosis. Clinicopathologic data available on 10 horses included hypocalcemia, hypomagnesemia, and azotemia. Cantharidin concentrations in urine or pooled gastric-cecal contents did not always correlate with severity of disease. Clinical Implications Blister beetle poisoning is not universally fatal in equids. Clinical signs are related to the amount of cantharidin ingested. Every horse that survived was treated aggressively. In fatal poisonings, gross lesions may be minimal or inapparent, and diagnosis must be confirmed by chemical detection of cantharidin in urine, blood, or stomach or cecal contents. (J Am Vet Med Assoc 1997;211:1018–1021)