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Sample records for ischemic canine myocardium

  1. Uptake of iodinated contrast material in ischemic myocardium as an indicator of loss of cellular membrane integrity.

    PubMed

    Abraham, J L; Higgins, C B; Newell, J D

    1980-11-01

    Differential uptake of iodine containing radiographic contrast medium (I) in myocardial infarcts compared with normal mycardium has been detected by computerized transmission tomography (CTT). In this study the histologic and cellular distribution of I in ischemically damaged canine myocardium after intravenous administration of contrast material was examined by the use of scanning electron microscopy and energy dispersive X-ray microanalysis of fresh frozen cryosections. Analysis of individual cells in 6-mu thick sections mounted on carbon substrates showed that I was detectable in the ischemically damaged but not the normal myocardial cells. A decline in the potassium-to-sodium ratio confirmed the loss of membrane integrity in the ischemically damaged cells that accumulated I. These results indicate that I enters ischemically damaged but not normal myocardial cells suggesting that CTT scans after intravenous administration of contrast material may be capable of defining the area of the myocardium in which cells have lost membrane integrity after an ischemic injury.

  2. Innate immune inflammatory response in the acutely ischemic myocardium.

    PubMed

    Deftereos, Spyridon; Angelidis, Christos; Bouras, Georgios; Raisakis, Konstantinos; Gerckens, Ulrich; Cleman, Michael W; Giannopoulos, Georgios

    2014-01-01

    The "holy grail" of modern interventional cardiology is the salvage of viable myocardial tissue in the distribution of an acutely occluded coronary artery. Thrombolysis and percutaneous coronary interventions, provided they can be delivered on time, can interrupt the occlusion and save tissue. At the same time restoring the patency of the coronary vessels and providing the ischemic myocardium with blood can cause additional tissue damage. A key element of ischemic and reperfusion injury and major determinant of the evolution of damage in the injured myocardium is the inflammatory response. The innate immune system initiates and directs this response which is a prerequisite for subsequent healing. The complement cascade is set in motion following the release of subcellular membrane constituents. Endogenous 'danger' signals known as danger-associated molecular patterns (DAMPs) released from ischemic and dying cells alert the innate immune system and activate several signal transduction pathways through interactions with the highly conserved Toll like receptors (TLRs). Reactive oxygen species (ROS) generation directly induces pro-inflammatory cascades and triggers formation of the inflammasome. The challenge lies into designing strategies that specifically block the inflammatory cascades responsible for tissue damage without affecting those concerned with tissue healing.

  3. Heat shock proteins, end effectors of myocardium ischemic preconditioning?

    PubMed Central

    Guisasola, María Concepcion; Desco, Maria del Mar; Gonzalez, Fernanda Silvana; Asensio, Fernando; Dulin, Elena; Suarez, Antonio; Garcia Barreno, Pedro

    2006-01-01

    The purpose of this study was to investigate (1) whether ischemia-reperfusion increased the content of heat shock protein 72 (Hsp72) transcripts and (2) whether myocardial content of Hsp72 is increased by ischemic preconditioning so that they can be considered as end effectors of preconditioning. Twelve male minipigs (8 protocol, 4 sham) were used, with the following ischemic preconditioning protocol: 3 ischemia and reperfusion 5-minute alternative cycles and last reperfusion cycle of 3 hours. Initial and final transmural biopsies (both in healthy and ischemic areas) were taken in all animals. Heat shock protein 72 messenger ribonucleic acid (mRNA) expression was measured by a semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR) method using complementary DNA normalized against the housekeeping gene cyclophilin. The identification of heat shock protein 72 was performed by immunoblot. In our “classic” preconditioning model, we found no changes in mRNA hsp72 levels or heat shock protein 72 content in the myocardium after 3 hours of reperfusion. Our experimental model is valid and the experimental techniques are appropriate, but the induction of heat shock proteins 72 as end effectors of cardioprotection in ischemic preconditioning does not occur in the first hours after ischemia, but probably at least 24 hours after it, in the so-called “second protection window.” PMID:17009598

  4. Uptake of iodinated contrast material in ischemic myocardium as an indicator of loss of cellular membrane integrity.

    PubMed Central

    Abraham, J. L.; Higgins, C. B.; Newell, J. D.

    1980-01-01

    Differential uptake of iodine containing radiographic contrast medium (I) in myocardial infarcts compared with normal mycardium has been detected by computerized transmission tomography (CTT). In this study the histologic and cellular distribution of I in ischemically damaged canine myocardium after intravenous administration of contrast material was examined by the use of scanning electron microscopy and energy dispersive X-ray microanalysis of fresh frozen cryosections. Analysis of individual cells in 6-mu thick sections mounted on carbon substrates showed that I was detectable in the ischemically damaged but not the normal myocardial cells. A decline in the potassium-to-sodium ratio confirmed the loss of membrane integrity in the ischemically damaged cells that accumulated I. These results indicate that I enters ischemically damaged but not normal myocardial cells suggesting that CTT scans after intravenous administration of contrast material may be capable of defining the area of the myocardium in which cells have lost membrane integrity after an ischemic injury. Images Figure 1 p[329]-a Figure 2 PMID:7435540

  5. [Efficacy of the myocardium cytoprotection in patients with ischemic heart disease during extended operations on abdominal organs].

    PubMed

    Mosienko, B I

    2013-09-01

    The results of studying of the myocardium contractile capacity in patients, suffering the ischemic heart disease, while performing the extended operative interventions are presented. There was noted, that the indices of the myocardium contractile capacity witness its inhibition during traumatic stage of operation and in early postoperative period. There was established an important significance of the myocardium cytoprotection in preoperative preparation of the patients.

  6. Computer simulation of the reentrant cardiac arrhythmias in ischemic myocardium.

    PubMed

    Zhang, Hong; Yang, Lin; Jin, Yin-bin; Zhang, Zhen-xi; Huang, Yi-zhuo

    2005-09-30

    Computer simulation was performed to determine how reentrant activity could occur due to the spatial heterogeneity in refractoriness induced by the regional ischemia. Two regional ischemic models were developed by decreasing the intracellular ATP concentration, reducing conductance of the inward Na+ current and increasing the extracellular K+ concentration on the two-dimensional sheet. Operator splitting method was used to integrate the models. The vulnerability to reentry was estimated from the timings of premature stimuli on the constructed models, which could result in unidirectionally propagating action potentials. Two kinds of sustained spiral waves and their Pseudo-Electroscardiograms were observed in numerical simulation. The results showed that the dispersion of refractory period increased with ischemic aggravation, and led to augment of the vulnerable window. A permature stimulation within the vulnerable window could easily induce spiral reentry. The Pseudo-Electrocardiograms of the spiral waves exhibited monomorphic tachycardiac waveforms. Thus, the spatial heterogeneity in refractoriness could be a substrate for reentrant ventricular tachyarrhythmias on the regional ischemic tissue.

  7. Effects of Momordica charantia (Bitter Melon) on Ischemic Diabetic Myocardium.

    PubMed

    Czompa, Attila; Gyongyosi, Alexandra; Szoke, Kitti; Bak, Istvan; Csepanyi, Evelin; Haines, David D; Tosaki, Arpad; Lekli, Istvan

    2017-03-20

    and ZO BM-treated, versus Lean rats of total cholesterol (high density lipoprotein HDL-c + low density lipoprotein LDL-c), with an inferred increase in HDL-c/LDL-c ratio-an outcome associated with decreased risk of atherosclerotic disease. Conclusions: BM extract failed to positively affect T2DM- and cardiovascular-related outcomes at a level suggesting use as a standalone treatment. Nevertheless, the encouraging effects of BM in enhancement of cardiac function, suppression of post-ischemic/reperfused infarct size extent and capacity to modulate serum cholesterol, will likely make it useful as an adjuvant therapy for the management of T2DM and related cardiovascular diseases.

  8. The iron-regulatory peptide hepcidin is upregulated in the ischemic and in the remote myocardium after myocardial infarction.

    PubMed

    Simonis, Gregor; Mueller, Katrin; Schwarz, Peggy; Wiedemann, Stephan; Adler, Guido; Strasser, Ruth H; Kulaksiz, Hasan

    2010-09-01

    Recent evidence suggests that iron metabolism contributes to the ischemic damage after myocardial infarction. Hepcidin, a recently discovered peptide hormone, regulates iron uptake and metabolism, protecting the body from iron overload. In this study we analyzed the regulation of hepcidin in the heart and blood of rats after myocardial infarction. To induce a myocardial infarction in the rats, left anterior descending coronary artery ligation was performed. After 1-24h, biopsies from the ischemic and the non-ischemic myocardium were taken. In these biopsies, the mRNA levels and the protein expression of hepcidin were analyzed by quantitative RT-PCR and immunoblot analysis, respectively. In parallel, the serum levels of prohepcidin were measured by ELISA. Six hours after myocardial infarction, the hepcidin mRNA expression was temporally upregulated in the ischemic and in the non-ischemic myocardium. The upregulation was specific for hepcidin, since other iron-related genes (hemojuvelin, IREG-1) remained unchanged. Furthermore, the alteration of the hepcidin protein expression in the ischemic area was connected to the level of hepcidin in the serum of the infarcted rats, where hepcidin also raised up. Angiotensin receptor blockade with candesartan did not influence the mRNA regulation of hepcidin. Together, these data show a particular upregulation of the iron-regulatory peptide hepcidin in the ischemic and the non-ischemic myocardium after myocardial infarction. It is speculated that upregulation of hepcidin may reduce iron toxicity and thus infarct size expansion in an infarcted heart.

  9. Passive targeting of ischemic-reperfused myocardium with adenosine-loaded silica nanoparticles

    PubMed Central

    Galagudza, Michael; Korolev, Dmitry; Postnov, Viktor; Naumisheva, Elena; Grigorova, Yulia; Uskov, Ivan; Shlyakhto, Eugene

    2012-01-01

    Pharmacological agents suggested for infarct size limitation have serious side effects when used at cardioprotective doses which hinders their translation into clinical practice. The solution to the problem might be direct delivery of cardioprotective drugs into ischemic-reperfused myocardium. In this study, we explored the potential of silica nanoparticles for passive delivery of adenosine, a prototype cardioprotective agent, into ischemic-reperfused heart tissue. In addition, the biodegradation of silica nanoparticles was studied both in vitro and in vivo. Immobilization of adenosine on the surface of silica nanoparticles resulted in enhancement of adenosine-mediated infarct size limitation in the rat model. Furthermore, the hypotensive effect of adenosine was attenuated after its adsorption on silica nanoparticles. We conclude that silica nanoparticles are biocompatible materials that might potentially be used as carriers for heart-targeted drug delivery. PMID:22619519

  10. Modified VEGF targets the ischemic myocardium and promotes functional recovery after myocardial infarction.

    PubMed

    Yang, Yun; Shi, Chunying; Hou, Xianglin; Zhao, Yannan; Chen, Bing; Tan, Bo; Deng, Zongwu; Li, Qingguo; Liu, Jianzhou; Xiao, Zhifeng; Miao, Qi; Dai, Jianwu

    2015-09-10

    Vascular endothelial growth factor (VEGF) promotes angiogenesis and improves cardiac function after myocardial infarction (MI). However, the non-targeted delivery of VEGF decreases its therapeutic efficacy due to an insufficient local concentration in the ischemic myocardium. In this study, we used a specific peptide to modify VEGF and determined that this modified VEGF (IMT-VEGF) localized to the ischemic myocardium through intravenous injection by interacting with cardiac troponin I (cTnI). When IMT-VEGF was used to mediate cardiac repair in a rat model of ischemia-reperfusion (I-R) injury, we observed a decreased scar size, enhanced angiogenesis and improved cardiac function. Moreover, an alternative treatment using the repeated administration of a low-dose IMT-VEGF also promoted angiogenesis and functional recovery. The therapeutic effects of IMT-VEGF were further confirmed in a pig model of MI as the result of the conserved properties of its interacting protein, cTnI. These results suggest a promising therapeutic strategy for MI based on the targeted delivery of IMT-VEGF.

  11. Spacial and temporal profiles of neutrophil accumulation in the reperfused ischemic myocardium.

    PubMed

    de Lorgeril, M; Rousseau, G; Basmadjian, A; St-Jean, G; Tran, D C; Latour, J G

    1990-01-01

    To elucidate further the pathogenic role of neutrophils in evolving reperfused myocardial infarction, we investigated the dynamics of their accumulation and distribution in the ischemic myocardium. The left anterior descending coronary artery was occluded in dogs for 2 hours followed by reperfusion for 0, 3, 6, or 24 hours. 111In-labeled neutrophils were injected at the time of occlusion or after 16 hours of reperfusion. The area at risk was similar among groups. Infarct size expressed in percent of the area at risk was identical between groups reperfused for 6 (35.2 +/- 4.4%) or 24 (32.3 +/- 3.9%) hours but smaller (22.0 +/- 4.4%; p less than 0.05) after 3 hours of reperfusion. 111In-neutrophils accumulation quantified by scintigraphy correlated positively with infarct size (r = 0.64, p less than 0.005); accumulation rates (cells/h/cm2MI) were high during the first 3 (2288 +/- 754) and 6 hours (1953 +/- 463) but low (490 +/- 192) between 16 and 24 hours of reperfusion. Cells accumulating during reperfusion (12,566 +/- 2307 cells/g at 3 hours) were found within the borders of the necrotic area, and the cell counts (2420 +/- 724 cells/g, p less than 0.05) in the live tissue located within the area at risk after 3 hours of reperfusion were similar to those found in the subepicardium at the onset of reperfusion: (2240 +/- 571 cells/g). Only a few cells were detected in the normally perfused myocardium (67 +/- 33 cells/g). We conclude that reperfusion accumulation in the ischemic myocardium; the reaction takes place within 3-6 hours of reperfusion, a period of time where infarct size is growing by about 40%. These results support the concept that leukocytes may play a pathogenic role on infarct size in models with brief ischemia followed by reperfusion.

  12. Ultrastructural and functional effects of lead poisoning on adult canine myocardium: assessment of thiamin treatment

    SciTech Connect

    Kincaid, N.G.

    1985-01-01

    The effects of lead (Pb) poisoning on the adult canine myocardium were assessed quantitatively using stereological techniques, functional testing, and blood analyses as well as qualitatively by morphological investigation. Relative measurements using stereological techniques compared the volume fractions of cellular components of the three groups. Blood was analyzed for lead, hemoglobin, hematocrit, total erythrocytes, total leukocytes, thiamin pyrophosphate (TPP), delta-aminolevulinic acid dehydratase activity (ALAD), and zinc protoporphyrin (ZPP). The major finding of the stereological analysis was the statistically significant increase of 3.2% in myofilament volume in the Pb treated group and the significant decrease in mitochondrial volume in both the Pb treated and Pb + B/sub 1/ treated groups. A statistically significant decrease in the mitochondria/myofilament volume ratio was found in the Pb treated, but no Pb + B/sub 1/ treated group. This may indicate either a protective effect of thiamin on mitochondria or a reduced compensatory need of the myocyte to increase myofilament volume.

  13. In vivo mechanical study of helical cardiac pacing electrode interacting with canine myocardium

    NASA Astrophysics Data System (ADS)

    Zhang, Xiangming; Ma, Nianke; Fan, Hualin; Niu, Guodong; Yang, Wei

    2007-06-01

    Cardiac pacing is a medical device to help human to overcome arrhythmia and to recover the regular beats of heart. A helical configuration of electrode tip is a new type of cardiac pacing lead distal tip. The helical electrode attaches itself to the desired site of heart by screwing its helical tip into the myocardium. In vivo experiments on anesthetized dogs were carried out to measure the acute interactions between helical electrode and myocardium during screw-in and pull-out processes. These data would be helpful for electrode tip design and electrode/myocardium adherence safety evaluation. They also provide reliability data for clinical site choice of human heart to implant and to fix the pacing lead. A special design of the helical tip using strain gauges is instrumented for the measurement of the screw-in and pull-out forces. We obtained the data of screw-in torques and pull-out forces for five different types of helical electrodes at nine designed sites on ten canine hearts. The results indicate that the screw-in torques increased steplike while the torque time curves presente saw-tooth fashion. The maximum torque has a range of 0.3 1.9 N mm. Obvious differences are observed for different types of helical tips and for different test sites. Large pull-out forces are frequently obtained at epicardium of left ventricle and right ventricle lateral wall, and the forces obtained at right ventricle apex and outflow tract of right ventricle are normally small. The differences in pull-out forces are dictated by the geometrical configuration of helix and regional structures of heart muscle.

  14. The altered expression profile of microRNAs in cardiopulmonary bypass canine models and the effects of mir-499 on myocardial ischemic reperfusion injury

    PubMed Central

    2013-01-01

    Background MicroRNAs were enrolled in various cardiovascular disease especially ischemic heart diseases, but the microRNA changes during myocardial ischemia reperfusion injury underwent cardiopulmonary bypass are still unknown. This study screens the microRNA differences in CPB canines and evaluates the relationship of microRNAs with myocardial ischemia reperfusion injury. Methods 13 healthy canines received CPB with 60 minutes of aortic clamping and cardioplegic arrest, followed by 90 minutes reperfusion. Left ventricular myocardial samples, blood samples and hemodynamic data were taken at different time points. We performed microRNAs microarray experiments upon the left ventricle myocardium tissue of canines before CPB and after reperfusion for 90 minutes by pooling 3 tissue samples together and used qRT-PCR for confirmation. Results Statistically significant difference was found in mir-499 level before CPB and after reperfusion (T1 vs. T4, p = 0.041). We further examined the mir-499 levels by using qRT-PCR in all 13 canines at 4 different time points (T1 vs. T4, p = 0.029). Mir-499 expression was negatively correlated with cardiac troponin T (cTnT) and creatine kinase- MB (CK-MB) levels of canines in all time points samples (r = 0.469, p < 0.001 and r = 0.273, p = 0.050 respectively). Moreover, higher mir-499 expression level was associated with higher dP/dtmax at 25 minutes and 90 minutes after reperfusion. Conclusion Myocardial ischemic reperfusion injury with cardiopulmonary bypass results in declining level of mir-499 expression in left ventricle myocardium of canines, suggesting mir-499 would be a potential therapeutic target in cardiac protection during open heart surgery. PMID:23800236

  15. Injectable shear-thinning hydrogels to deliver endothelial progenitor cells, enhance cell engraftment, and improve ischemic myocardium

    PubMed Central

    Gaffey, Ann C.; Chen, Minna H.; Venkataraman, Chantel M.; Trubelja, Alen; Rodell, Christopher B.; Dinh, Patrick V.; Hung, George; MacArthur, John W.; Soopan, Renganaden V.; Burdick, Jason A.; Atluri, Pavan

    2015-01-01

    OBJECTIVES The clinical translation of cell based therapies for ischemic heart disease has been limited due to low cell retention (<1%) within and poor targeting to ischemic myocardium. To address these issues, we developed an injectable shear-thinning hyaluronic acid hydrogel (STG) and endothelial progenitor cell construct (STG-EPC). The STG assembles due to interactions of adamantine and β-cyclodextrin modified hyaluronic acid. It is shear-thinning to permit delivery via a syringe, and self-heals upon injection within the ischemic myocardium. This directed therapy to the ischemic myocardial borderzone enables direct cell delivery to address adverse remodeling after myocardial infarction. We hypothesize that this system will enhance vasculogenesis to improve myocardial stabilization in the context of a clinically translatable therapy. METHODS EPCs (DiLDL+ VEGFR2+ CD34+) were harvested from adult male Wistar Rats, cultured, and then suspended in the STG. In vitro viability was quantified using a live-dead stain of EPCs. STG-EPC constructs were injected at the borderzone of ischemic rat myocardium after acute myocardial infarction (left anterior descending coronary artery ligation). The migration of the eGFP+ EPCs from the construct to ischemic myocardium was analyzed using fluorescent microscopy. Vasculogenesis, myocardial remodeling, and hemodynamic function were analyzed in 4 groups: control (PBS injection), intramyocardial injection of EPCs alone (EPC), injection of the STG alone (STG), and treatment with the gel-EPC construct (STG-EPC). Hemodynamics and ventricular geometry were quantified using echocardiography and Doppler flow analysis. RESULTS EPCs demonstrated viability within the STG. A marked increase in EPC engraftment was observed one-week post-injection within the treated myocardium with gel delivery when compared to EPC injection alone (17.2 ± 0.8 cells/HPF vs. 3.5 cells ± 1.3 cells/HPF, p = 0.0002). A statistically significant increase in

  16. Targeting delivery of Radix Ophiopogonis polysaccharide to ischemic/reperfused rat myocardium by long-circulating macromolecular and liposomal carriers

    PubMed Central

    Wang, LiNa; Yao, ChunXia; Wu, Fei; Lin, Xiao; Shen, Lan; Feng, Yi

    2015-01-01

    Drug delivery to ischemic myocardium is an enormous challenge. This work aimed to characterize cardiac delivery behaviors of mono-polyethylene glycosylated (PEGylated) conjugates and long-circulating liposomes (L-Lps) with Radix Ophiopogonis polysaccharide (ROP) as drug. The results showed that compared to native ROP, 32-, 52-, and 45-fold increases in blood half-life were achieved by 20-kDa PEG mono-modified ROP (P20k-R), 40-kDa PEG mono-modified ROP (P40k-R), and ROP-loaded L-Lp, respectively. With comparable blood pharmacokinetics, ROP-loaded L-Lp showed both significantly higher targeting efficacy and drug exposure in infarcted myocardium than P40k-R. With regard to P20k-R, both its targeting efficacy and its level in infarcted myocardium at 3 hours postdose were comparable to P40k-R, but its level in blood and myocardium reduced obviously faster. As a whole, the results indicate that both loading in L-Lps and mono-PEGylation are effective in targeting drug to ischemic myocardium, but the former appears to induce stronger effects. PMID:26425081

  17. Bone marrow and bone marrow derived mononuclear stem cells therapy for the chronically ischemic myocardium

    SciTech Connect

    Waksman, Ron; Baffour, Richard

    2003-09-01

    Bone marrow stem cells have been shown to differentiate into various phenotypes including cardiomyocytes, vascular endothelial cells and smooth muscle. Bone marrow stem cells are mobilized and home in to areas of injured myocardium where they are involved in tissue repair. In addition, bone marrow secretes multiple growth factors, which are essential for angiogenesis and arteriogenesis. In some patients, these processes are not enough to avert clinical symptoms of ischemic disease. Therefore, in vivo administration of an adequate number of stem cells would be a significant therapeutic advance. Unfractionated bone marrow derived mononuclear stem cells, which contain both hematopoietic and nonhematopoietic cells may be more appropriate for cell therapy. Studies in animal models suggest that implantation of different types of stem cells improve angiogenesis and arteriogenesis, tissue perfusion as well as left ventricular function. Several unanswered questions remain. For example, the optimal delivery approach, dosage and timing of the administration of cell therapy as well as durability of improvements need to be studied. Early clinical studies have demonstrated safety and feasibility of various cell therapies in ischemic disease. Randomized, double blind and placebo-controlled clinical trials need to be completed to determine the effectiveness of stem cell.

  18. Relationship between Tl-201, Tc-99m (Sn) pyrophosphate and F-18 2-deoxyglucose uptake in ischemically injured dog myocardium

    SciTech Connect

    Sochor, H.; Schwaiger, M.; Schelbert, H.R.; Huang, S.C.; Ellison, D.; Hansen, H.; Selin, C.; Parodi, O.; Phelps, M.E.

    1987-11-01

    We have previously demonstrated that enhanced glucose utilization in reperfused myocardium as assessed by F-18 2-deoxyglucose (FDG) and positron tomography predicts functional recovery. In this study, we compared segmental uptake of F-18 FDG with that of Tl-201 and Tc-99m (Sn) pyrophosphate (Tc-99m PPi) as conventional markers of tissue viability in seven dogs after a 3-hour intracoronary balloon occlusion and 20 hours of reperfusion. Myocardial blood flow was determined with microspheres. Regional retention fractions were calculated from tracer tissue concentrations, the arterial input function, and blood flow. Ischemic injury was assessed by triphenyltetrazolium chloride (TTC) staining and histologic analysis. At 24 hours, blood flow was 22% lower in reperfused than in control myocardium (p less than 0.05). Uptake of Tl-201 was related linearly to blood flow (r = 0.92), while glucose utilization and Tc-99m PPi were 2.9 (p less than 0.01) and 4.7 (p less than 0.05) times higher in reperfused than in control myocardium. Retention fractions of Tc-99m PPi increased with the degree of ischemic injury, while F-18 FDG uptake was highest in segments with mild cell injury. Thus, in ischemically injured myocardium, Tl-201 primarily reflects blood flow. F-18 FDG as a marker of glucose utilization identifies ischemically injured but viable tissue. The admixture of necrotic cells can be determined with Tc-99m PPi. Our results indicate that a dual tracer approach might best characterize the presence and extent of reversibly and of irreversibly injured tissue in a given myocardial region.

  19. Localization of viable, ischemic myocardium by positron-emission tomography with /sup 11/C-palmitate

    SciTech Connect

    Lerch, R.A.; Ambos, H.D.; Bergmann, S.R.; Welch, M.J.; Ter-Pogossian, M.M.; Sobel, B.E.

    1981-10-01

    A study was performed to determine whether viable, but ischemic, tissue could be detected and localized in vivo based on external detection of impaired fatty acid metabolism. Accordingly, regional clearance of /sup 11/C-palmitate was assessed by sequential PET in 15 anesthetized dogs. Clearance was consistently monoexponential from 5-15 minutes after administration of the tracer. In the absence of coronary stenosis (n = 7), clearance was homogeneous throughout the heart, with an average rate constant (k) of -0.060 +/- 0.005 min/sup -1/ (+/- SEM) and a coefficient of variation (CV) of 11.1 +/- 2.1% in each heart. Homogeneity persisted when the heart rate was increased from 84.4 +/- 6.0 to 202.7 +/- 11.5 beats/min with atropine (CV 13.2 +/- 3.5%). With left circumflex coronary stenosis (less than or equal to70% reduction in vessel diameter), homogeneity of /sup 11/C-clearance under control conditions and with tachycardia did not differ from clearance in hearts without coronary stenosis. However, with stenosis >70% sufficient to induce ischemia without gross infarction, regional clearance of /sup 11/C became markedly heterogeneous under control conditions (CV 28.1 +/- 5.5%, p <0.01 compared with normal hearts) and with tachycardia (CV 34.8 +/- 5.4%, p <0.01). The heterogeneity resulted from reduced clearance of /sup 11/C in regions supplied by the stenotic vessel (k = -0.044 +/- 0.011 min/sup -1/) compared with clearance in well perfused regions (k = -0.064 +/- 0.011 min/sup -1/, p <0.025), a difference accentuated by tachycardia. Thus, sequential PET after i.v. injection of /sup 11/C-palmitate delineates zones of viable, ischemic myocardium that characteristically exhibit impaired oxidation of extracted fatty acid.

  20. Improvement in Myocardial Function and Coronary Blood Flow in Ischemic Myocardium after Mannitol

    PubMed Central

    Willerson, James T.; Powell, Wm. John; Guiney, Timothy E.; Stark, James J.; Sanders, Charles A.; Leaf, Alexander

    1972-01-01

    The purpose of this study was to evaluate the effect of hyperosmolality on the performance of, and the collateral blood flow to, ischemic myocardium. The myocardial response to mannitol, a hyperosmolar agent which remains extracellular, was evaluated in anesthetized dogs. Mannitol was infused into the aortic roots of 31 isovolumic hearts and of 15 dogs on right heart bypass, before and during ischemia. Myocardial ischemia was produced by temporary ligation of either the proximal or mid-left anterior descending coronary artery. Mannitol significantly improved the depressed ventricular function curves which occurred with left anterior descending coronary artery occlusion. Mannitol also significantly lessened the S-T segment elevation (epicardial electrocardiogram) occurring during myocardial ischemia in the isovolumic hearts and this reduction was associated with significant increases in total coronary blood flow (P < 0.005) and with increased collateral coronary blood flow to the ischemia area (P < 0.005). Thus, increases in serum osmolality produced by mannitol result in the following beneficial changes during myocardial ischemia: (a) improved myocardial function, (b) reduced S-T segment elevation, (c) increased total coronary blood flow, and (d) increased collateral coronary blood flow. PMID:4640943

  1. In Vivo Functional and Transcriptional Profiling of Bone Marrow Stem Cells after Transplantation into Ischemic Myocardium

    PubMed Central

    Sheikh, Ahmad Y.; Huber, Bruno C.; Narsinh, Kazim H.; Spin, Joshua M.; van der Bogt, Koen; de Almeida, Patricia E.; Ransohoff, Katherine J.; Kraft, Daniel L.; Fajardo, Giovanni; Ardigo, Diego; Ransohoff, Julia; Bernstein, Daniel; Fischbein, Michael P.; Robbins, Robert C.; Wu, Joseph C.

    2011-01-01

    Objective Clinical trials of bone marrow-derived stem cell therapy for the heart have yielded variable results. The basic mechanism(s) that underlie their potential efficacy remains unknown. In the present study, we evaluate the survival kinetics, transcriptional response, and functional outcome of intramyocardial bone marrow mononuclear cell (BMMC) transplantation for cardiac repair in murine myocardial infarction model. Methods and Results We utilized molecular-genetic bioluminescence imaging and high throughput transcriptional profiling to evaluate the in vivo survival kinetics and gene expression changes of transplanted BMMCs after their engraftment into ischemic myocardium. Our results demonstrate short-lived survival of cells following transplant, with less than 1% of cells surviving by 6 weeks post-transplantation. Moreover, transcriptomic analysis of BMMCs revealed non-specific upregulation of various cell regulatory genes with a marked downregulation of cell differentiation and maturation pathways. BMMC therapy caused limited improvement of heart function as assessed by echocardiography, invasive hemodynamics, and positron emission tomography (PET). Histological evaluation of cell fate further confirmed findings of the in vivo cell tracking and transcriptomic analysis. Conclusions Collectively, these data suggest that BMMC therapy, in its present iteration, may be less efficacious than once thought. Additional refinement of existing cell delivery protocols should be considered to induce better therapeutic efficacy. PMID:22034515

  2. Effects of ischemic preconditioning on myocardium Caspase-3, SOCS-1, SOCS-3, TNF-α and IL-6 mRNA expression levels in myocardium IR rats.

    PubMed

    Ma, Jiangwei; Qiao, Zengyong; Xu, Biao

    2013-10-01

    The aim of this study was to characterise the effects of ischemic preconditioning (IP) on heart function parameters (ΔST and ΔT), activities of serum creatine kinase (CK), lactate dehydrogenase (LDH), and levels of serum nitric oxide (NO), malondialdehyde (MDA), and myocardium Caspase-3 mRNA, SOCS-1, SOCS-3, tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) expression levels and Apoptosis index in myocardium IR rats. Results showed that ΔST and ΔST values in IP group were markedly lower than those in IR group. Compared with IR group, IP significantly (p < 0.01) decreased serum CK (0.83 ± 0.09 vs 1.36 ± 0.15), LDH (5613 ± 462 vs 7106 ± 492) activities and MDA (11.32 ± 1.05 vs 15.49 ± 1.26) level, increased the serum NO (86.39 ± 7.03 vs 53.77 ± 4.27) level in IR group. The IP induced a significant decreased in myocardium Caspase-3 mRNA (0.303 ± 0.021 vs 0.515 ± 0.022) gene expression (p < 0.01) compared to IR model group. The IP induced a significant decreased in myocardium SOCS-1 (0.241 ± 0.031 vs 0.596 ± 0.036), SOCS-3 (0.258 ± 0.031 vs 0.713 ± 0.057), TNF-α (0.137 ± 0.011 vs 0.427 ± 0.035) and IL-6 (0.314 ± 0.021 vs 0.719 ± 0.064) mRNA gene expression (p < 0.01) compared to IR model group. We conclude that IP is effective in the therapy of heart disease. These findings may have implications for the clinical development of preconditioning-based therapies for ischemic heart disease.

  3. Electrical remodeling in a canine model of ischemic cardiomyopathy.

    PubMed

    Liu, Xian-Sheng; Jiang, Min; Zhang, Mei; Tang, Daniel; Clemo, Henry F; Higgins, Robert S D; Tseng, Gea-Ny

    2007-01-01

    The nature of electrical remodeling in a canine model of ischemic cardiomyopathy (ICM; induced by repetitive intracoronary microembolizations) that exhibits spontaneous ventricular tachycardia is not entirely clear. We used the patch-clamp technique to record action potentials and ionic currents of left ventricular myocytes isolated from the region affected by microembolizations. We also used the immunoblot technique to examine channel subunit expression in adjacent affected tissue. Ventricular myocytes and tissue isolated from the corresponding region of normal hearts served as control. ICM myocytes had prolonged action potential duration (APD) and more pronounced APD dispersion. Slow delayed rectifier current (I(Ks)) was reduced at voltages positive to 0 mV, along with a negative shift in its voltage dependence of activation. Immunoblots showed that there was no change in KCNQ1.1 (I(Ks) pore-forming or alpha-subunit), but KCNE1 (I(Ks) auxiliary or beta-subunit) was reduced, and KCNQ1.2 (a truncated KCNQ1 splice variant with a dominant-negative effect on I(Ks)) was increased. Transient outward current (I(to)) was reduced, along with an acceleration of the slow phase of recovery from inactivation. Immunoblots showed that there was no change in Kv4.3 (alpha-subunit of fast-recovering I(to) component), but KChIP2 (beta-subunit of fast-recovering component) and Kv1.4 (alpha-subunit of slow-recovering component) were reduced. Inward rectifier current was reduced. L-type Ca current was unaltered. The immunoblot data provide mechanistic insights into the observed changes in current amplitude and gating kinetics of I(Ks) and I(to). We suggest that these changes, along with the decrease in inward rectifier current, contribute to APD prolongation in ICM hearts.

  4. Remote ischemic postconditioning enhances cell retention in the myocardium after intravenous administration of bone marrow mesenchymal stromal cells.

    PubMed

    Jiang, Qin; Song, Peng; Wang, Enshi; Li, Jun; Hu, Shengshou; Zhang, Hao

    2013-03-01

    Efficacy of intravenous administration of mesenchymal stromal cells (MSCs) for myocardial infarction (MI) is limited by low cell retention in the damaged myocardium. Previous studies indicated that remote ischemic conditioning could protect against ischemia-reperfusion-induced injury by release of various cytokines including stromal cell derived factor-1 alpha (SDF-1α). However, whether remote ischemic postconditioning (RIPostC) can also enhance the retention of infused cells in the myocardium by activating MSC homing is unclear. In this study, RIPostC was induced with 4cycles of 5min occlusion and reperfusion of the abdominal aorta in female Sprague-Dawley (SD) rats which underwent ligation of the coronary artery 1week previously. Cytokine levels in serum and myocardium were evaluated by enzyme-linked immunosorbent assay (ELISA) at 1, 6, 24 and 48h after RIPostC. Then, a total of 4×10(6) male MSCs were infused intravenously at 24h after RIPostC. The number of survived cells in the myocardium was evaluated by real-time polymerase chain reaction analysis for Y chromosome and the heart function was evaluated by echocardiography at 1month after cell infusion. Furthermore, 10μg/kg rabbit anti-rat CXCR4 polyclonal antibody was injected intraperitoneally to prove the role of SDF-1α for RIPostC. RIPostC induced an increase in SDF-1α in serum at 1h and enhanced SDF-1α transcription and protein synthesis in the myocardium at 24h after the procedure. 1month after cell transplantation, RIPostC significantly increased MSC myocardial retention by 79.1±12.3% and thereby contributed to enhanced cardiac function in comparison with cell transplantation without RIPostC. Furthermore, blockade with a CXCR4-specific antibody after RIPostC markedly attenuated the enhancement of therapeutic efficacy. We conclude that RIPostC activated SDF-1α expression and enhanced retention of the infused MSCs in the injured myocardium. Priming of the heart with RIPostC might be a novel

  5. The role of insulin-like and basic fibroblast growth factors on ischemic and infarcted myocardium: a mini review.

    PubMed

    Scheinowitz, M; Abramov, D; Eldar, M

    1997-03-01

    Current therapeutic techniques in acute myocardial infarction (AMI) are inadequate since restoration of blood flow through the obstructed coronary artery does not always preserve the ischemic myocardium. Therefore, deterioration of cardiac function and detrimental left ventricular remodeling may follow. Alternative therapeutic modalities are now being actively sought. Insulin-like growth factor (IGF) and fibroblast growth factor (FGF) are two polypeptides found in wide distribution and high concentrations in the normal myocardium. They play a key role in vascular growth (FGF) and affect the differentiation of cardiac myocytes (IGF). IGF has been found to promote physiological forms of cardiac hypertrophy, and FGF induces neovascularization. During myocardial ischemia and infarction there is a marked elevation in the concentration of these growth promoting factors in the myocardium concomitant with increased coronary collateral blood flow, neovascularization and peri-infarct hypertrophy. In animal models of myocardial infarction, exogenous administration of FGF and IGF induced neovascularization and cardiac hypertrophy thus, preserving cardiac function. We assume that these growth factors may become an additional tool in the future treatment of patients with AMI.

  6. Lack of cardiac nerve sprouting after intramyocardial transplantation of bone marrow-derived stem cells in a swine model of chronic ischemic myocardium.

    PubMed

    Liu, Yuan; Lai, Wing-Hon; Liao, Song-Yan; Siu, Chung-Wah; Yang, Yan-Zong; Tse, Hung-Fat

    2012-06-01

    Previous experimental studies suggested that mesenchymal stem cell transplantation causes cardiac nerve sprouting; however, whether bone marrow (BM)-derived mononuclear cells (MNC) and endothelial progenitor cells (EPC) can also lead to cardiac nerve sprouting and alter gap junction expression remains unclear. We investigated the effect of electroanatomical mapping-guided direct intramyocardial transplantation of BM-MNC (n = 8) and CD31+EPC (n = 8) compared with saline control (n = 8) on cardiac nerve sprouting and gap junction expression in a swine model of chronic ischemic myocardium. At 12 weeks after transplantation, the distribution and density of cardiac nerve sprouting were determined by staining of tyrosine hydroxylase (TH) and growth associated protein 43(GAP-43) and expression of connexin 43 in the targeted ischemic and remote normal myocardium. After 12 weeks, no animal developed sudden death after the transplantation. There were no significant differences in the number of cells with positive staining of TH and GAP-43 in the ischemic and normal myocardium between three groups. Furthermore, expression of connexin 43 was also similar in the ischemic and normal myocardia in each group of animals (P > 0.05). The results of this study demonstrated that intramyocardial BM-derived MNC or EPC transplantation in a large animal model of chronic myocardial ischemia was not associated with increased cardiac nerve sprouting over the ischemic myocardium.

  7. Two forms of spiral-wave reentry in an ionic model of ischemic ventricular myocardium

    NASA Astrophysics Data System (ADS)

    Xu, Aoxiang; Guevara, Michael R.

    1998-03-01

    It is well known that there is considerable spatial inhomogeneity in the electrical properties of heart muscle, and that the many interventions that increase this initial degree of inhomogeneity all make it easier to induce certain cardiac arrhythmias. We consider here the specific example of myocardial ischemia, which greatly increases the electrical heterogeneity of ventricular tissue, and often triggers life-threatening cardiac arrhythmias such as ventricular tachycardia and ventricular fibrillation. There is growing evidence that spiral-wave activity underlies these reentrant arrhythmias. We thus investigate whether spiral waves might be induced in a realistic model of inhomogeneous ventricular myocardium. We first modify the Luo and Rudy [Circ. Res. 68, 1501-1526 (1991)] ionic model of cardiac ventricular muscle so as to obtain maintained spiral-wave activity in a two-dimensional homogeneous sheet of ventricular muscle. Regional ischemia is simulated by raising the external potassium concentration ([K+]o) from its nominal value of 5.4 mM in a subsection of the sheet, thus creating a localized inhomogeneity. Spiral-wave activity is induced using a pacing protocol in which the pacing frequency is gradually increased. When [K+]o is sufficiently high in the abnormal area (e.g., 20 mM), there is complete block of propagation of the action potential into that area, resulting in a free end or wave break as the activation wave front encounters the abnormal area. As pacing continues, the free end of the activation wave front traveling in the normal area increasingly separates or detaches from the border between normal and abnormal tissue, eventually resulting in the formation of a maintained spiral wave, whose core lies entirely within an area of normal tissue lying outside of the abnormal area ("type I" spiral wave). At lower [K+]o (e.g., 10.5 mM) in the abnormal area, there is no longer complete block of propagation into the abnormal area; instead, there is partial

  8. Improving the cardio protective effect of aFGF in ischemic myocardium with ultrasound-mediated cavitation of heparin modified microbubbles: preliminary experiment.

    PubMed

    Zhao, Ying-Zheng; Lu, Cui-Tao; Li, Xiao-Kun; Tang, Qin-Qin; Tian, Xin-Qiao; Zhao, Ya-Ping; Zhang, Yan; Tian, Ji-Lai; Yang, Wei; Ge, Shuping; Nair, Chandra K; Shen, Xuedong

    2012-08-01

    Ultrasound (US)-mediated cavitation of microbubbles has evolved into a new tool for organ-specific gene and drug delivery. This paper was to investigate the feasibility of acidic fibroblast growth factor (aFGF) intravenous delivery to the ischemic myocardium of rats by ultrasonic microbubbles modified with heparin. Heparin modified microbubbles (HMB) were prepared by the freeze-dried method. Acute myocardial infarction (AMI) model was established and the cardio protective effect of the aFGF combing with HMB (aFGF-HMB) under US-mediated cavitation technique was investigated. aFGF-HMB combined with US-mediated cavitation technique was examined by ECG. Ejection fraction (EF), fractional shortening (FS) and left ventricular diastolic diameter (LVDd) were measured to monitor the improvement of global myocardial contractile function. Myocardial tissue was stained with hematoxylin and eosine (HE) to evaluate the elaborate general morphology of the ischemic myocardium. From morphologic observation and echocardiography in rat heart, aFGF-HMB had suitable size distribution, physical stability and good acoustic resonance function. From AMI rat experiments, aFGF-HMB under US-mediated cavitation technique exerted aFGF cardio protective effect in ischemic myocardium. From histological evaluation, US-mediated cavitation of aFGF-HMB showed improvement of myocardial ischemia. With the visual imaging and US-triggered drug release advantages, US-mediated cavitation of aFGF-HMB might be developed as a novel technique for targeting delivery of aFGF into ischemic myocardium.

  9. [Emoxipin in reperfusion of ischemic myocardium in dogs: effects on infarct size and plasma creatine kinase activity].

    PubMed

    Konorev, E A; Polumiskov, V Iu; Avilova, O A; Golikova, A P

    1990-09-01

    The effects of synthetic antioxidant emoxypine on infarct size and plasma creatine kinase (CK) activity was studied on open-chest anesthetized dogs with 180-min myocardial ischemia followed by reperfusion. Emoxypine (10 and 40 mg/kg) was injected intravenously, beginning since 120th min of coronary artery occlusion. Emoxypine (10 mg/kg) resulted in infarct size limitation and reduction in plasma CK activity. An increase in dose of emoxypine to 40 mg/kg largely attenuated its protective effect on infarct size. CK activity during post-ischemic reperfusion was even higher in emoxypine (40 mg/kg) group compared with control. Augmented CK leakage from irreversibly injured myocardium to plasma under these experimental conditions may be owing to preservation of microvascular integrity and improving of drainage of infarcted tissue exerted by emoxypine.

  10. In vivo protein transduction: delivery of PEP-1-SOD1 fusion protein into myocardium efficiently protects against ischemic insult.

    PubMed

    Zhang, You-En; Wang, Jia-Ning; Tang, Jun-Ming; Guo, Ling-Yun; Yang, Jian-Ye; Huang, Yong-Zhang; Tan, Yan; Fu, Shou-Zhi; Kong, Xia; Zheng, Fei

    2009-02-28

    Myocardial ischemia-reperfusion injury is a medical problem occurring as damage to the myocardium following blood flow restoration after a critical period of coronary occlusion. Oxygen free radicals (OFR) are implicated in reperfusion injury after myocardial ischemia. The antioxidant enzyme, Cu, Zn-superoxide dismutase (Cu, Zn-SOD, also called SOD1) is one of the major means by which cells counteract the deleterious effects of OFR after ischemia. Recently, we reported that a PEP-1-SOD1 fusion protein was efficiently delivered into cultured cells and isolated rat hearts with ischemia-reperfusion injury. In the present study, we investigated the protective effects of the PEP-1-SOD1 fusion protein after ischemic insult. Immunofluorescecnce analysis revealed that the expressed and purified PEP-1-SOD1 fusion protein injected into rat tail veins was efficiently transduced into the myocardium with its native protein structure intact. When injected into Sprague-Dawley rat tail veins, the PEP-1- SOD1 fusion protein significantly attenuated myocardial ischemia-reperfusion damage; characterized by improving cardiac function of the left ventricle, decreasing infarct size, reducing the level of malondialdehyde (MDA), decreasing the release of creatine kinase (CK) and lactate dehydrogenase (LDH), and relieving cardiomyocyte apoptosis. These results suggest that the biologically active intact forms of PEP-1-SOD1 fusion protein will provide an efficient strategy for therapeutic delivery in various diseases related to SOD1 or to OFR.

  11. Tissue Engineered, Hydrogel-Based Endothelial Progenitor Cell Therapy Robustly Revascularizes Ischemic Myocardium and Preserves Ventricular Function

    PubMed Central

    Atluri, Pavan; Miller, Jordan S; Emery, Robert J; Hung, George; Trubelja, Alen; Cohen, Jeffrey E; Lloyd, Kelsey; Han, Jason; Gaffey, Ann C; MacArthur, John W; Chen, Christopher S; Woo, Y Joseph

    2014-01-01

    Objective Cell based angiogenic therapy for ischemic heart failure has had limited clinical impact, likely related to very low cell retention (<1%) and dispersion. We developed a novel, tissue engineered, hydrogel based cell delivery strategy to overcome these limitations and provide prolonged regional retention of myocardial endothelial progenitor cells (EPC) at high cell dosage. Methods EPCs were isolated from Wistar Rats and encapsulated in fibrin gels. In vitro viability was quantified using a fluorescent live-dead stain of transgenic eGFP+ EPCs. EPC-laden constructs were implanted onto ischemic rat myocardium in a model of acute myocardial infarction (LAD ligation) for 4 weeks. Intramyocardial cell injection (IC, 2×106 EPCs), empty fibrin, and isolated LAD ligation groups served as controls. Hemodynamics were quantified using echocardiography, Doppler flow analysis, and intraventricular pressure-volume analysis. Vasculogenesis and ventricular geometry were quantified. EPC migration was analyzed by utilizing EPCs from transgenic eGFP+ rodents. Results EPCs demonstrated an overall 88.7% viability for all matrix and cell conditions investigated after 48 hours. Histologic assessment of 1-wk implants demonstrated significant migration of transgenic eGFP+ EPCs from the fibrin matrix to the infarcted myocardium as compared to IC (28±12.3 vs. 2.4±2.1cells/hpf, p=0.0001). We also observed a marked increase in vasculogenesis at the implant site. Significant improvements in ventricular hemodynamics and geometry were present following EPC-hydrogel therapy as compared to control. Conclusion We present a tissue engineered hydrogel-based EPC mediated therapy to enhance cell delivery, cell retention, vasculogenesis, and preservation of myocardial structure and function. PMID:25129603

  12. Spatially Oriented, Temporally Sequential Smooth Muscle Cell-Endothelial Progenitor Cell Bi-Level Cell Sheet Neovascularizes Ischemic Myocardium

    PubMed Central

    Shudo, Yasuhiro; Cohen, Jeffrey E.; MacArthur, John W.; Atluri, Pavan; Hsiao, Philip F.; Yang, Elaine C.; Fairman, Alexander S.; Trubelja, Alen; Patel, Jay; Miyagawa, Shigeru; Sawa, Yoshiki; Woo, Y. Joseph

    2014-01-01

    Background Endothelial progenitor cells (EPCs) possess robust therapeutic angiogenic potential, yet may be limited in the capacity to develop into fully mature vasculature. This problem might be exacerbated by the absence of a neovascular foundation, namely pericytes, with simple EPC injection. We hypothesized that coculturing EPCs with smooth muscle cells (SMCs), components of the surrounding vascular wall, in a cell sheet will mimic the native spatial orientation and interaction between EPCs and SMCs to create a supratherapeutic angiogenic construct in a model of ischemic cardiomyopathy. Methods and Results Primary EPCs and SMCs were isolated from Wistar rats. Confluent SMCs topped with confluent EPCs were spontaneously detached from the Upcell dish to create an SMC-EPC bi-level cell sheet. A rodent ischemic cardiomyopathy model was created by ligating the left anterior descending coronary artery. Rats were then immediately divided into 3 groups: cell-sheet transplantation (n=14), cell injection (n=12), and no treatment (n=13). Cocultured EPCs and SMCs stimulated an abundant release of multiple cytokines in vitro. Increased capillary density and improved blood perfusion in the borderzone elucidated the significant in vivo angiogenic potential of this technology. Most interestingly, however, cell fate–tracking experiments demonstrated that the cell-sheet EPCs and SMCs directly migrated into the myocardium and differentiated into elements of newly formed functional vasculature. The robust angiogenic effect of this cell sheet translated to enhanced ventricular function as demonstrated by echocardiography. Conclusions Spatially arranged EPC-SMC bi-level cell-sheet technology facilitated the natural interaction between EPCs and SMCs, thereby creating structurally mature, functional microvasculature in a rodent ischemic cardiomyopathy model, leading to improved myocardial function. PMID:24030422

  13. Fluorescence lifetime measurements of NADH and tryptophan in intact ischemic, intact rabbit myocardium

    NASA Astrophysics Data System (ADS)

    Hamburger, Adrian; Gryczynski, Zygmunt; Lakowicz, Joseph R.; Sommers, Keith

    1999-07-01

    Ischemia-reperfusion injury is the leading cause of early dysfunction following transplantation. Currently, there are no techniques available to accurately measure ischemic changes during organ storage. Therefore, the interest exists in developing non-invasive monitoring techniques. We used NADH and tryptophan as fluorescent markers, since both are intrinsic fluorophores and excellent indicators for levels of hypoxia and protein denaturation, respectively.

  14. Segmenting high-frequency intracardiac ultrasound images of myocardium into infarcted, ischemic, and normal regions.

    PubMed

    Hao, X; Bruce, C J; Pislaru, C; Greenleaf, J F

    2001-12-01

    Segmenting abnormal from normal myocardium using high-frequency intracardiac echocardiography (ICE) images presents new challenges for image processing. Gray-level intensity and texture features of ICE images of myocardium with the same structural/perfusion properties differ. This significant limitation conflicts with the fundamental assumption on which existing segmentation techniques are based. This paper describes a new seeded region growing method to overcome the limitations of the existing segmentation techniques. Three criteria are used for region growing control: 1) Each pixel is merged into the globally closest region in the multifeature space. 2) "Geographic similarity" is introduced to overcome the problem that myocardial tissue, despite having the same property (i.e., perfusion status), may be segmented into several different regions using existing segmentation methods. 3) "Equal opportunity competence" criterion is employed making results independent of processing order. This novel segmentation method is applied to in vivo intracardiac ultrasound images using pathology as the reference method for the ground truth. The corresponding results demonstrate that this method is reliable and effective.

  15. Kinetics of a putative hypoxic tissue marker, Technetium-99m-nitroimidazole (BMS181321), in normoxic, hypoxic, ischemic and stunned myocardium

    SciTech Connect

    Kusuoka, Hideo; Hashimoto, Katsuji; Fukuchi, Kazuki

    1994-08-01

    This study focused on the kinetics of the newly developed {sup 99m}TTc-nitroimidazole, propyleneamine oxime-1,2-nitroimidazole (BMS181321) in the different setting of myocardial perfusion states and oxygenation levels, and compared the kinetics of BMS181321 with those of other technetium analogues. The kinetics of BMS181321 were evaluated in isolated perfused rat hearts. Technetium-99m-hexamethyl propyleneamine oxime (HMPAO) and a non-nitroimidazole-containing analogue of BMS 181321 (6-methyl propyleneamine oxime; PAO-6-Me) were used to compare their kinetics with those of BMS181321. BMS181321 cleared quickly from normoxic hearts and the retention in the myocardium 10 min after injection was 0.84% {plus_minus} 0.04% ID/g wet wt (mean {plus_minus} s.e.m.). In contrast, BMS181321 was retained after reperfusion when it was injected before ischemia; the uptake in the myocardium 10 min after reperfusion was significantly greater than in controls (23.9% {plus_minus} 3.9%ID/g wt, p<0.05). These results indicate that {sup 99m}Tc-BMS181321 is well trapped in ischemic myocardium and moderately trapped in hypoxic myocardium, but washed out quickly in stunned myocardium. The residence time influences the amount retained. 14 refs., 7 figs., 1 tab.

  16. Identification of ischemic and hibernating myocardium: feasibility of post-exercise F-18 deoxyglucose positron emission tomography

    SciTech Connect

    Marwick, T.H.; MacIntyre, W.J.; Salcedo, E.E.; Go, R.T.; Saha, G.; Beachler, A. )

    1991-02-01

    The identification of ischemic and hibernating myocardium facilitates the selection of patients most likely to benefit from revascularization. This study examined the feasibility of metabolic imaging, using post-exercise F-18 deoxyglucose positron emission tomography (FDG-PET) for the diagnosis of both ischemia and hibernation in 27 patients with known coronary anatomy. Normal post-exercise FDG uptake was defined in each patient by reference to normal resting perfusion and normal coronary supply. Abnormal elevation of FDG (ischemia or hibernation) was compared in 13 myocardial segments in each patient, with the results of dipyridamole stress perfusion imaging performed by rubidium-82 positron emission tomography (Rb-PET). Myocardial ischemia was diagnosed by either FDG-PET or Rb-PET in 34 segments subtended by significant local coronary stenoses. Increased FDG uptake was present in 32/34 (94%) and a reversible perfusion defect was identified by Rb-PET in 22/34 (65%, p less than .01). In 3 patients, ischemia was identified by metabolic imaging alone. In 16 patients with previous myocardial infarction, perfusion defects were present at rest in 89 regions, 30 of which (34%) demonstrated increased FDG uptake, consistent with the presence of hibernation. Increased post-exercise FDG uptake appears to be a sensitive indicator of ischemia and myocardial hibernation. Increased post-exercise FDG uptake, appears to be a sensitive indicator of ischemia and myocardial hibernation. This test may be useful in selecting post-infarction patients for revascularization.

  17. Modulation of ephrinB2 leads to increased angiogenesis in ischemic myocardium and endothelial cell proliferation

    SciTech Connect

    Mansson-Broberg, Agneta; Siddiqui, Anwar J.; Genander, Maria; Grinnemo, Karl-Henrik; Hao Xiaojin; Andersson, Agneta B.; Waerdell, Eva; Sylven, Christer Corbascio, Matthias

    2008-08-29

    Eph/ephrin signaling is pivotal in prenatal angiogenesis while its potential role in postnatal angiogenesis largely remains to be explored. Therefore its putative angiogenic and therapeutic effects were explored in endothelium and in myocardial ischemia. In culture of human aortic endothelial cells the fusion protein ephrinB2-Fc induced cell proliferation (p < 0.0005) and in the murine aortic ring model ephrinB2-Fc induced increased sprouting (p < 0.05). Myocardial infarction was induced by ligation of the left anterior descending artery in mouse. During the following 2 weeks mRNA of the receptor/ligand pair EphB4/ephrinB2 was expressed dichotomously (p < 0.05) and other Eph/ephrin pairs were expressed to a lesser degree. Twenty-four hours after intraperitoneal administration of ephrinB2-Fc it was detected in abundance throughout the myocardium along capillaries, showing signs of increased mitosis. After 4 weeks the capillary density was increased 28% in the periinfarcted area (p < 0.05) to a level not different from healthy regions of the heart where no change was observed. These results implicate that EphB4/ephrinB2 is an important signaling pathway in ischemic heart disease and its modulation may induce therapeutic angiogenesis.

  18. Stimulus-induced critical point. Mechanism for electrical initiation of reentry in normal canine myocardium.

    PubMed

    Frazier, D W; Wolf, P D; Wharton, J M; Tang, A S; Smith, W M; Ideker, R E

    1989-03-01

    The hypothesis was tested that the field of a premature (S2) stimulus, interacting with relatively refractory tissue, can create unidirectional block and reentry in the absence of nonuniform dispersion of recovery. Simultaneous recordings from a small region of normal right ventricular (RV) myocardium were made from 117 to 120 transmural or epicardial electrodes in 14 dogs. S1 pacing from a row of electrodes on one side of the mapped area generated parallel activation isochrones followed by uniform parallel isorecovery lines. Cathodal S2 shocks of 25 to 250 V lasting 3 ms were delivered from a mesh electrode along one side of the mapped area to scan the recovery period, creating isogradient electric field lines perpendicular to the isorecovery lines. Circus reentry was created following S2 stimulation; initial conduction was distant from the S2 site and spread towards more refractory tissue. Reentry was clockwise for right S1 (near the septum) with top S2 (near the pulmonary valve) and for left S1 with bottom S2; and counterclockwise for right S1 with bottom S2 and left S1 with top S2. The center of the reentrant circuit for all S2 voltages and coupling intervals occurred at potential gradients of 5.1 +/- 0.6 V/cm (mean +/- standard deviation) and at preshock intervals 1 +/- 3 ms longer than refractory periods determined locally for a 2 mA stimulus. Thus, when S2 field strengths and tissue refractoriness are uniformally dispersed at an angle to each other, circus reentry occurs around a "critical point" where an S2 field of approximately 5 V/cm intersects tissue approximately at the end of its refractory period.

  19. Cardiac progenitor-derived exosomes protect ischemic myocardium from acute ischemia/reperfusion injury

    SciTech Connect

    Chen, Lijuan; Wang, Yingjie; Pan, Yaohua; Zhang, Lan; Shen, Chengxing; Qin, Gangjian; Ashraf, Muhammad; Weintraub, Neal; Ma, Genshan; Tang, Yaoliang

    2013-02-15

    Highlights: ► Cardiac progenitor-derived (CPC) Exosomes protect H9C2 from apoptosis in vitro. ► CPC-exosomes protect cardiomyoyctes from MI/R induced apoptosis in vivo. ► CPC-exosomes were taken up by H9C2 with high efficiency using PKH26 labeling. ► miR-451, one of GATA4-responsive miRNA cluster, is enriched in CPC-exosomes. -- Abstract: Background: Cardiac progenitors (CPC) mediate cardioprotection via paracrine effects. To date, most of studies focused on secreted paracrine proteins. Here we investigated the CPC-derived-exosomes on protecting myocardium from acute ischemia/reperfusion (MI/R) injury. Methods and results: CPC were isolated from mouse heart using two-step protocol. Exosomes were purified from conditional medium, and confirmed by electron micrograph and Western blot using CD63 as a marker. qRT-PCR shows that CPC-exosomes have high level expression of GATA4-responsive-miR-451. Exosomes were ex vivo labeled with PKH26, We observed exosomes can be uptaken by H9C2 cardiomyoblasts with high efficiency after 12 h incubation. CPC-exosomes protect H9C2 from oxidative stress by inhibiting caspase 3/7 activation invitro. In vivo delivery of CPC-exosomes in an acute mouse myocardial ischemia/reperfusion model inhibited cardiomyocyte apoptosis by about 53% in comparison with PBS control (p < 0.05). Conclusion: Our results suggest, for the first time, the CPC-exosomes can be used as a therapeutic vehicle for cardioprotection, and highlights a new perspective for using non-cell exosomes for cardiac disease.

  20. Control of interval-force relation in canine ventricular myocardium studied with ryanodine.

    PubMed Central

    Bose, D.; Hryshko, L. V.; King, B. W.; Chau, T.

    1988-01-01

    1. The mechanism of post-extrasystolic, rest and frequency potentiation was studied in canine isolated ventricular muscle. 2. Ryanodine, which impairs Ca availability from the sarcoplasmic reticulum (SR), reduced the amplitude of the extrasystole less than that of the steady state contraction. Ryanodine also inhibited post-extrasystolic potentiation and converted rest-potentiation into rest depression. Rest-potentiation was blocked preferentially by ryanodine compared to post-extrasystolic potentiation. An increase in the contribution of extracellular Ca to the extrasystolic contraction could not entirely account for the post-extrasystolic potentiation. 3. Prolonged rest, by itself, also caused depression of the first post-rest contraction. During rest-potentiation, SR Ca seemed to play a greater role in contraction than transmembrane Ca influx. However, the ability of the 'release pool' of Ca in the SR to be reprimed after a contraction was reduced. This was seen as a decrease in post-extrasystolic potentiation elicited immediately after rest. 4. A decrease in stimulus interval was associated with a transient decrease in contraction amplitude followed by an increase. An abrupt increase in stimulus interval had the opposite effect. Ryanodine blocked the initial transient changes and accelerated the delayed changes. These results suggest that the transient changes in contraction after sudden changes in drive interval are dependent on the SR. 5. Transmembrane Ca entry and the rate of recovery of the Ca release process (repriming) in the SR after a contraction seem to be interval-dependent. The data also indicate that different mechanisms are involved in post-extrasystolic and rest-potentiation. 6. The results are consistent with a model which proposes 'recirculation' of activator Ca within the SR after a contraction or of the presence of an appreciable amount of inactivation of the SR Ca release process during normal stimulation. An increased pool of releasable Ca

  1. Effects of purified herbal extract of Salvia miltiorrhiza on ischemic rat myocardium after acute myocardial infarction.

    PubMed

    Sun, Jian; Huang, Shan Hong; Tan, Benny K-H; Whiteman, Matt; Zhu, Yi Chun; Wu, Ya Jun; Ng, Yeekong; Duan, Wei; Zhu, Yi Zhun

    2005-04-29

    In the current study, we compared purified Salvia miltiorrhiza extract (PSME) with Angiotensin-converting enzyme inhibitor, Ramipril, in in vitro experiments and also in vivo using animal model of myocardial infarction. PSME was found to have a significantly higher trolox equivalent antioxidant capacity which indicated a great capacity for scavenging free radicals. PSME could also prevent pyrogallo red bleaching and DNA damage. After 2 weeks treatment with PSME or Ramipril, survival rates of rats with experimental myocardial infarction were marginally increased (68.2% and 71.4%) compared with saline (61.5%). The ratios of infarct size to left ventricular size in both PSME-and Ramipril-treated rats were significantly less than that in the saline-treated group. Activity of cardiac antioxidant enzyme superoxide dismutase (SOD) was significant higher while level of Thiobarbituric acid-reactive substances (TBARs) was lower in the PSME treated group. Purified and standardized Chinese herb could provide an alternative regimen for the prevention of ischemic heart disease.

  2. Response of cyt a,a3 in the situ canine heart to transient ischemic episodes.

    PubMed

    Snow, T R; Kleinmann, L H; LaManna, J C; Wechsler, A S; Jöbsis, F F

    1981-01-01

    Experiments were performed to examine the response of cyt a,a3 to transient ischemic and hypoxic episodes in the empty, fibrillating canine heart in situ. Using a dual wavelength, differential spectrophotometer, reaction spectra show an absorption peak at approximately 605 nm consistent with that obtained from purified cyt a,a3. The characteristics of the averaged reaction spectrum in the interval 590 nm to 610 nm indicate that hemoglobin/myoglobin contribute no more than 23% to the signal measured at 605 nm. A regimen of one 30 sec global ischemia (GI) repeated once every 3 minutes over a 90 min period showed no appreciable signal deterioration. Therefore, five such interventions were subsequently used as the test perturbation. Studies of the effects of ischemic episodes of 30 and 60 min show that the response of cyt a,a3 to this test intervention was smaller (90 +/- 6% and 89 +/- 7%) than that observed prior to the ischemic episode. Changes in coronary perfusion pressure (+/- 10 Torr) produced an immediate oxidation/reduction of cyt a,a3. In the working heart, just prior to fibrillation, 6 sec to interrupted ventilation resulted in a continuous reduction of cyt a,a3. The data from these studies show: 1) The redox state of cyt a,a3 may be continuously monitored in the canine heart in situ. 2) Following ischemias of 30 and 60 min duration, respiratory chain function may be impaired; and 3) The well-perfused epicardium is extremely sensitive to small changes in oxygen delivery.

  3. Pathology of acute ischemic myocardium. Special references to (I) evaluation of morphological methods for detection of early myocardial infarcts, and (II) lipid metabolism in infarcted myocardium.

    PubMed

    Sakurai, I

    1977-09-01

    Morphological changes of early myocardial infarction within 24 hours after the onset of the acute attack were described together with a review of the literatures. For the practical purpose in detecting very early infarcts, enzymatic histochemistry is the most reliable method. Other methods previously reported such as wavy pattern of the muscle fibers and fuchsinophilia are still controvertial. Lipid metabolism in the infarcted myocardium of dogs was studied both morphologically and biochemically. Up to 3 hours, after the coronary ligation, the tissue lipids accumulated in the necrotic areas with a rise of triglyceride, but later than 6 hours the lipids decreased and were lost from the necrotic tissue, while the surrounding living cells were accumulated with neutral lipids. Serum free fatty acids were elevated in the coronary sinus blood in 6 hours after the ligation. Linolic acids were contained in high proportion in both coronary venous blood after 6 hours, and normal myocardial phospholipid. These results may lead to another possible factor in addition to catecholamine activity to elevate serum FFA in acute myocardial infarction that fatty acids may be released partly from tissue phospholipid and once ever accumulated triglyceride.

  4. Chronic left atrial volume overload abbreviates the action potential duration of the canine pulmonary vein myocardium via activation of IK channel.

    PubMed

    Nouchi, Hideaki; Takahara, Akira; Nakamura, Hideki; Namekata, Iyuki; Sugimoto, Takahiko; Tsuneoka, Yayoi; Takeda, Kiyoshi; Tanaka, Toshikazu; Shigenobu, Koki; Sugiyama, Atsushi; Tanaka, Hikaru

    2008-11-12

    Electrophysiological properties of the pulmonary vein myocardium were assessed in a canine chronic atrioventricular block model resulting in left atrial volume overload. Five chronic atrioventricular block dogs and five sham-operated dogs were used. The heart was removed two months after a surgical procedure causing atrioventricular block, when atrial structural remodeling was established. Standard microelectrode penetrations were made with glass microelectrodes to obtain action potential signals of left atrium and pulmonary vein myocardia. The resting membrane potential in the pulmonary vein was more positive than that in the left atrium (-69 mV vs -74 mV) in both animal groups. The action potential duration at 50% repolarization of the pulmonary vein was shorter in the chronic atrioventricular block dogs than in the sham-operated dogs (38 ms vs 63 ms), whereas no significant difference was detected in the action potential duration of the left atrium between the two animal groups (67 ms vs 61 ms). The action potential duration of the pulmonary vein in the chronic atrioventricular block dogs was prolonged by charybdotoxin but not by iberiotoxin. Such prolongation was not observed in the normal pulmonary vein. These results suggest that long-term left atrial dilatation shortened the action potential duration of pulmonary vein myocardium, which may be associated with activation of the intermediate conductance Ca2+-activated K+ channel (IK channel).

  5. Effect of exercise training and myocardial infarction on force development and contractile kinetics in isolated canine myocardium.

    PubMed

    Canan, Benjamin D; Haizlip, Kaylan M; Xu, Ying; Monasky, Michelle M; Hiranandani, Nitisha; Milani-Nejad, Nima; Varian, Kenneth D; Slabaugh, Jessica L; Schultz, Eric J; Fedorov, Vadim V; Billman, George E; Janssen, Paul M L

    2016-04-15

    It is well known that moderate exercise training elicits a small increase in ventricular mass (i.e., a physiological hypertrophy) that has many beneficial effects on overall cardiac health. It is also well known that, when a myocardial infarction damages part of the heart, the remaining myocardium remodels to compensate for the loss of viable functioning myocardium. The effects of exercise training, myocardial infarction (MI), and their interaction on the contractile performance of the myocardium itself remain largely to be determined. The present study investigated the contractile properties and kinetics of right ventricular myocardium isolated from sedentary and exercise trained (10-12 wk progressively increasing treadmill running, begun 4 wk after MI induction) dogs with and without a left ventricular myocardial infarction. Exercise training increased force development, whereas MI decreased force development that was not improved by exercise training. Contractile kinetics were significantly slower in the trained dogs, whereas this impact of training was less or no longer present after MI. Length-dependent activation, both evaluated on contractile force and kinetics, was similar in all four groups. The control exercise-trained group exhibited a more positive force-frequency relationship compared with the sedentary control group while both sedentary and trained post-MI dogs had a more negative relationship. Last, the impact of the β-adrenergic receptor agonist isoproterenol resulted in a similar increase in force and acceleration of contractile kinetics in all groups. Thus, exercise training increased developed force but slowed contractile kinetics in control (noninfarcted animals), actions that were attenuated or completely absent in post-MI dogs.

  6. Fibrin patch-based insulin-like growth factor-1 gene-modified stem cell transplantation repairs ischemic myocardium

    PubMed Central

    Li, Jun; Zhu, Kai; Yang, Shan; Wang, Yulin; Guo, Changfa; Yin, Kanhua; Wang, Chunsheng

    2015-01-01

    Bone marrow mesenchymal stem cells (BMSCs), tissue-engineered cardiac patch, and therapeutic gene have all been proposed as promising therapy strategies for cardiac repair after myocardial infarction. In our study, BMSCs were modified with insulin-like growth factor-1 (IGF-1) gene, loaded into a fibrin patch, and then transplanted into a porcine model of ischemia/reperfusion (I/R) myocardium injury. The results demonstrated that IGF-1 gene overexpression could promote proliferation of endothelial cells and cardiomyocyte-like differentiation of BMSCs in vitro. Four weeks after transplantation of fibrin patch loaded with gene-modified BMSCs, IGF-1 overexpression could successfully promote angiogenesis, inhibit remodeling, increase grafted cell survival and reduce apoptosis. In conclusion, the integrated strategy, which combined fibrin patch with IGF-1 gene modified BMSCs, could promote the histological cardiac repair for a clinically relevant porcine model of I/R myocardium injury. PMID:25767192

  7. [Neurogenic stunned myocardium].

    PubMed

    Ruiz Bailén, M; Rucabado Aguilar, L; López Martínez, A

    2006-01-01

    The existence of stunned myocardium and reversible myocardial dysfunction is widely described and accepted in patients suffering ischemic heart disease. However, it cannot be exclusive to coronary disease. Classically, the appearance of electrocardiographic changes in the critical neurological disease has been described. However, at present, it seems to be observed that some of these patients with critical neurological disease could have variable grades of myocardial dysfunction, which is generally reversible in the surviving patients. This myocardial dysfunction, which could affect critically ill neurological patients, has traits similar to stunned myocardium generated in coronary patients since: a) it is generally associated to electrocardiographic changes, b) it can be accompanied by segmental contractility disorders and even c) it may be accompanied by a certain increase of cardiac biomarkers. Although its etiopathogeny is unknown, it could be related with the severity of the primary neurological disease. Its prophylaxis and prognosis are also unknown. It could be related with neurogenic edema, with hemodynamic instability, and could also play a very important role in brain death and in organ donation.

  8. Protective effect of pretreatment with the calcium antagonist anipamil on the ischemic-reperfused rat myocardium: a phosphorus-31 nuclear magnetic resonance study

    SciTech Connect

    Kirkels, J.H.; Ruigrok, T.J.; Van Echteld, C.J.; Meijler, F.L.

    1988-05-01

    To assess whether the prophylactic administration of anipamil, a new calcium antagonist, protects the heart against the effects of ischemia and reperfusion, rats were injected intraperitoneally twice daily for 5 days with 5 mg/kg body weight of this drug. The heart was then isolated and perfused by the Langendorff technique. Phosphorus-31 nuclear magnetic resonance spectroscopy was used to monitor myocardial energy metabolism and intracellular pH during control perfusion and 30 min of total ischemia (37/sup 0/C), followed by 30 min of reperfusion. Pretreatment with anipamil altered neither left ventricular developed pressure under normoxic conditions nor the rate and extent of depletion of adenosine triphosphate (ATP) and creatine phosphate during ischemia. Intracellular acidification, however, was attenuated. On reperfusion, hearts from anipamil-pretreated animals recovered significantly better than untreated hearts with respect to replenishment of ATP and creatine phosphate stores, restitution of low levels of intracellular inorganic phosphate and recovery of left ventricular function and coronary flow. Intracellular pH recovered rapidly to preischemic levels, whereas in untreated hearts a complex intracellular inorganic phosphate peak indicated the existence of areas of different pH within the myocardium. It is concluded that anipamil pretreatment protects the heart against some of the deleterious effects of ischemia and reperfusion. Because this protection occurred in the absence of a negative inotropic effect during normoxia, it cannot be attributed to an energy-sparing effect during ischemia. Therefore, alternative mechanisms of action are to be considered.

  9. A quantitative index of regional blood flow in canine myocardium derived noninvasively with N-13 ammonia and dynamic positron emission tomography

    SciTech Connect

    Nienaber, C.A.; Ratib, O.; Gambhir, S.S.; Krivokapich, J.; Huang, S.C.; Phelps, M.E.; Schelbert, H.R. )

    1991-01-01

    To derive a quantitative index of regional myocardial blood flow, the arterial input function of the flow tracer N-13 ammonia and the regional myocardial N-13 activity concentrations were noninvasively determined in 29 experiments in eight dogs. N-13 ammonia was administered intravenously and cross-sectional images were acquired dynamically using an ECAT III positron emission tomograph with an effective in-plane resolution of 13.46 mm full-width half-maximum. Time-activity curves were derived from the serial images by assigning regions of interest to the left ventricular myocardium and left ventricular blood pool. Tracer net extractions were estimated from the myocardial time-activity concentrations at various times after tracer injection and the integral of the arterial input function. Myocardial blood flow was altered by intravenous dipyridamole, morphine, propranolol and partial or complete occlusion of the left anterior descending coronary artery, and ranged from 9 to 860 ml/min per 100 g. Estimates of tracer net extractions were most accurate when determined from the myocardial N-13 activity concentrations at 60 s divided by the integral of the arterial input function to that time. These estimates correlated with regional myocardial blood flows determined independently by the microsphere technique by y = x (1 - 0.64(e-114/x); SEE = 22.9; r = 0.94). First pass extraction fractions of N-13 ammonia determined noninvasively with this approach declined with higher flows in a nonlinear fashion and were similar to those determined invasively by direct intracoronary N-13 ammonia injections. The findings indicate that an accurate index of regional myocardial blood flow can be obtained noninvasively by high temporal sampling of arterial and myocardial tracer activity concentrations with positron emission tomography.

  10. Using Next-generation RNA Sequencing to Examine Ischemic Changes Induced by Cold Blood Cardioplegia on the Human Left Ventricular Myocardium Transcriptome

    PubMed Central

    Muehlschlegel, Jochen D.; Christodoulou, Danos C.; McKean, David; Gorham, Joshua; Mazaika, Erica; Heydarpour, Mahyar; Lee, Grace; DePalma, Steven R.; Perry, Tjorvi E.; Fox, Amanda F.; Shernan, Stanton; Seidman, Christine E.; Aranki, Sary F.; Seidman, Jon G.; Body, Simon C.

    2014-01-01

    Background The exact mechanisms that underlie the pathological processes of myocardial ischemia in humans are unclear. Cardiopulmonary bypass with cardioplegic arrest allows us to examine the whole transcriptional profile of human left ventricular myocardium at baseline and after exposure to cold cardioplegia induced ischemia as a human ischemia model. Methods We obtained biopsies from 45 patients undergoing aortic valve replacement surgery at baseline and after an average of 79 min of cold cardioplegic arrest. Samples were RNA-sequenced and analyzed with the Partek Genomics Suite for differential expression. Ingenuity Pathway Analysis and Biobase Explain systems were used for functional and pathway analysis. Results Of the 4,098 genes with a mean expression value greater than 5, 90% were downregulated and 9.1% were upregulated. Of those, 1,241 were significantly differentially expressed. Gene ontology analysis revealed significant downregulation in immune inflammatory response and complement activation categories, and highly consistent was the downregulation of intelectin 1, proteoglycan, and SLPI. Upregulated genes of interest were FBJ murine osteosarcoma viral oncogene homolog (FOS) and the hemoglobin genes hemoglobin 1 (HBA1) and hemoglobin beta (HBB). In addition, analysis of transcription factor binding sites revealed interesting targets in factors regulating reactive oxygen species production, apoptosis, immunity, cytokine production, and inflammatory response. Conclusions We have shown that the human left ventricle exhibits significant changes in gene expression in response to cold cardioplegia induced ischemia during cardiopulmonary bypass which provides great insight into the pathophysiology of ventricular ischemia, and thus, may help guide efforts to reduce myocardial damage during surgery. PMID:25581909

  11. Effects of transmyocardial laser revascularization using a prototype pulsed CO2 laser on contractility and perfusion of chronically ischemic myocardium in a porcine model

    NASA Astrophysics Data System (ADS)

    Wadia, Yasmin; Khaki, Ali; Kajitani, Michio; Mori, Yoshiki; Irvine, Timothy; Sahn, David; Yessik, Michael J.; Bahlman, Deborah T.; Furnary, Anthony; Gregory, Kenton W.

    1999-06-01

    The purpose of this study was to test a new prototype pulsed CO2 laser to be used for transmyocardial laser revascularization (TMR). We want to determine whether it can reduce thermal damage and mitigate induced ischemia with improvement in contractile reserve of the heart as evidenced by contrast echocardiography at rest and under dobutamine stress. TMR is an emerging surgical strategy for treatment of myocardial ischemia not amenable to conventional percutaneous or surgical revascularization. Eleven pigs underwent amaroid occulder placement on the origin of the circumflex coronary artery. Six weeks laser occlusion of the circumflex coronary artery was documented. TMR was then done on ten pigs using a prototype pulsed CO2 laser that delivered 8-12 joules energy in 1.5ms with a spot sizes of 1mm. Six weeks after TMR the pigs were restudied and sacrificed. The animals developed significant ischemia after six weeks of ameroid occlusion, at rest (p=0.01) and at peak stress (p=0.004). Wall motion for the ischemic segments improved significantly six weeks after TMR at peak stress (p=0.02). TMR results in an improvement in wall motion in our model of chromic ischemia and improves WMSI significantly during induced stress than at rest.

  12. Improved myocardium transducer

    NASA Technical Reports Server (NTRS)

    Culler, V. H.; Feldstein, C.; Lewis, G. W.

    1979-01-01

    Method of implanting myocardium transducer uses special indented pins that are caught and securely held by epicardial fibers. Pins are small enough to cause minimum of trauma to myocardium during implantation or removal.

  13. Angiogenesis in the Infarcted Myocardium

    PubMed Central

    Cochain, Clement; Channon, Keith M.

    2013-01-01

    Abstract Significance: Proangiogenic therapy appeared a promising strategy for the treatment of patients with acute myocardial infarction (MI), as de novo formation of microvessels, has the potential to salvage ischemic myocardium at early stages after MI, and is also essential to prevent the transition to heart failure through the control of cardiomyocyte hypertrophy and contractility. Recent Advances: Exciting preclinical studies evaluating proangiogenic therapies for MI have prompted the initiation of numerous clinical trials based on protein or gene transfer delivery of growth factors and administration of stem/progenitor cells, mainly from bone marrow origin. Nonetheless, these clinical trials showed mixed results in patients with acute MI. Critical Issues: Even though methodological caveats, such as way of delivery for angiogenic growth factors (e.g., protein vs. gene transfer) and stem/progenitor cells or isolation/culture procedure for regenerative cells might partially explain the failure of such trials, it appears that delivery of a single growth factor or cell type does not support angiogenesis sufficiently to promote cardiac repair. Future Directions: Optimization of proangiogenic therapies might include stimulation of both angiogenesis and vessel maturation and/or the use of additional sources of stem/progenitor cells, such as cardiac progenitor cells. Experimental unraveling of the mechanisms of angiogenesis, vessel maturation, and endothelial cell/cardiomyocyte cross talk in the ischemic heart, analysis of emerging pathways, as well as a better understanding of how cardiovascular risk factors impact endogenous and therapeutically stimulated angiogenesis, would undoubtedly pave the way for the development of novel and hopefully efficient angiogenesis targeting therapeutics for the treatment of acute MI. Antioxid. Redox Signal. 18, 1100–1113. PMID:22870932

  14. Enhancement of canine coronary collateral flow by nafazatrom.

    PubMed

    Fiedler, V B; Mardin, M

    1986-11-04

    The ability of oral nafazatrom treatment (10 mg/kg) 2 h preceding occlusion of the left anterior descending coronary artery for 6 h to limit expansion of myocardial injury was studied in anaesthetized canine hearts. Collateral blood flow was obtained with a load line analysis, employing aortic pressure, post-stenotic coronary pressure, and retrograde coronary flow from the occluded vessel. Contractile changes in the subendocardial ischemic perfused muscles were measured with ultrasonic techniques. Infarct size was determined post-mortem by a biochemical staining method and excision of necrosis. Post-stenotic coronary pressure was slightly below aortic pressure in both groups before coronary occlusion, and fell to 29 and 27% of aortic pressure in vehicle- and drug-treated hearts, respectively, after the insult. Retrograde flow was 2.4 +/- 0.6 vs. 4.1 +/- 0.7 ml/min in tylose- or nafazatrom-treated hearts. Collateral flow amounted to 1.5 +/- 0.06 vs. 2.5 +/- 0.04 ml/min in controls and drug-protected hearts. Contractility (dP/dtmax) and the %-segment shortening were greater in the ischaemic myocardium after nafazatrom treatment. Infarct size was 38 +/- 5.2 vs. 17 +/- 3.4 g/100 g left ventricle in the vehicle controls and nafazatrom group, respectively. Nafazatrom reduced infarct size by 46%. Besides other mechanisms, this was due to improved %-segment shortening and increased periinfarction collateral blood supply to jeopardized but viable myocardium. The drug may be of value in ischaemic heart disease as shown by the enhanced regional myocardial perfusion and improved contractility.

  15. Ischemic Stroke

    MedlinePlus

    A stroke is a medical emergency. There are two types - ischemic and hemorrhagic. Ischemic stroke is the most common type. It is usually ... are at risk for having a more serious stroke. Symptoms of stroke are Sudden numbness or weakness ...

  16. Shock-induced arrhythmogenesis in the myocardium

    NASA Astrophysics Data System (ADS)

    Trayanova, Natalia; Eason, James

    2002-09-01

    The focus of this article is the investigation of the electrical behavior of the normal myocardium following the delivery of high-strength defibrillation shocks. To achieve its goal, the study employs a complex three-dimensional defibrillation model of a slice of the canine heart characterized with realistic geometry and fiber architecture. Defibrillation shocks of various strengths and electrode configurations are delivered to the model preparation in which a sustained ventricular tachycardia is induced. Instead of analyzing the post-shock electrical events as progressions of transmembrane potential maps, the study examines the evolution of the postshock phase singularities (PSs) which represent the organizing centers of reentry. The simulation results demonstrate that the shock induces numerous PSs the majority of which vanish before the reentrant wavefronts associated with them complete half of a single rotation. Failed shocks are characterized with one or more PSs that survive the initial period of PS annihilation to establish a new postshock arrhythmia. The increase in shock strength results in an overall decrease of the number of PSs that survive over 200 ms after the end of the shock; however, the exact behavior of the PSs is strongly dependent on the shock electrode configuration.

  17. Genetic modification of stem cells for improved therapy of the infarcted myocardium.

    PubMed

    Haider, Husnain Kh; Mustafa, Anique; Feng, Yuliang; Ashraf, Muhammad

    2011-10-03

    The conventional treatment modalities for ischemic heart disease only provide symptomatic relief to the patient without repairing and regenerating the damaged myocardium. Stem cell transplantation has emerged as a promising alternative therapeutic approach for cardiovascular diseases. Stem cells possess the potential of differentiation to adopt morphofunctional cardiac and vasculogenic phenotypes to repopulate the scar tissue and restore regional blood flow in the ischemic myocardium. These beneficial therapeutic effects make stem cell transplantation the method of choice for the treatment of ischemic heart disease. The efficacy of stem cell transplantation may be augmented by genetic manipulation of the cells prior to transplantation. Not only will insertion of therapeutic transgene(s) into the stem cells support the survival and differentiation of cells in the unfavorable microenvironment of the ischemic myocardium, but also the genetically manipulated stem cells will serve as a source of the transgene expression product in the heart for therapeutic benefits. We provide an overview of the extensively studied stem cell types for cardiac regeneration, the various methods in which these cells have been genetically manipulated and rationale of genetic modification of stem cells for use in regenerative cardiovascular therapeutics.

  18. Canine Distemper

    MedlinePlus

    ... and, often, the nervous systems of puppies and dogs. The virus also infects wild canids (e.g. ... How is Canine Distemper virus spread? Puppies and dogs usually become infected through airborne exposure to the ...

  19. Canine lymphoma.

    PubMed

    Madewell, B R

    1985-07-01

    This article presents an overview of the literature regarding canine malignant lymphoma. It includes a discussion of etiology, classification, systemic manifestations of disease, therapy, and supportive care for patient management.

  20. Canine gastritis.

    PubMed

    Webb, Craig; Twedt, David C

    2003-09-01

    Gastritis--inflammation of the stomach--is a frequently cited differential yet rarely characterized diagnosis in cases of canine anorexia and vomiting. Although the list of rule-outs for acute or chronic gastritis is extensive, a review of the veterinary literature reveals fewer than 15 articles that have focused on clinical cases of canine gastritis over the last 25 years. The dog frequently appears in the human literature as an experimentally manipulated model for the study of endoscopic techniques or the effect of medications on gastric mucosa. In the veterinary patient, cases of acute gastritis are rarely pursued with the complete diagnostic armamentarium, and cases of chronic gastritis are rarely found to occur as an entity isolated from the rest of the gastrointestinal tract. This article focuses on those findings most clinically relevant to cases of canine gastritis in veterinary medicine.

  1. Increased expression of Dock180 protein in the noninfarcted myocardium in rats.

    PubMed

    Liu, Xiao-Lan; Li, Gang; Wang, Zhi-Hua; Zhao, Wen-Ju; Wang, Li-Ping

    2013-03-01

    The integrin β1 subunit and its downstream molecule focal adhesion kinase have been identified as critical molecules for the inhibition of postinfarction cardiac remodeling, ischemic cardiomyopathy, and heart failure. However, as a component of the integrin pathway, it is still unclear whether Dock180 (dedicator of cytokinesis 1) protein is expressed in the noninfarcted myocardium of the peri-infarct zones. In this study, experimental myocardial infarction (MI) and sham-operation (sham) models were established in Sprague Dawley rats and the expression of Dock180 protein in the myocardium of the sham group and in the noninfarcted myocardium of the peri-infarct zones of the MI group was detected by Western blot technique. The Dock180 protein expression in the myocardium was as follows: postsham 24-hour group, 0.10 ± 0.04 (n = 8); post-MI 24-hour group, 0.13 ± 0.03 (n = 8); postsham 12-week group, 0.11 ± 0.05 (n = 8); and post-MI 12-week group 0.17 ± 0.04 (n = 8). The Dock180 protein expression in the myocardium in the post-MI 12-week group was significantly higher than that in the postsham 12-week group (p = 0.019), in the postsham 24-hour group (p = 0.004), and in the post-MI 24-hour group (p = 0.040). We conclude that Dock180 protein is expressed in the myocardium in rats. Furthermore, its expression is significantly increased in the noninfarcted myocardium of the peri-infarct zones.

  2. [Ultrastructural changes in the undamaged areas of the myocardium in rats with ischaemic-metabolic cardiomyopathy (author's transl)].

    PubMed

    Zlatewa, M; Angelow, A

    1980-01-01

    The ultrastructural changes in the undamaged areas of the myocardium in rats with ischemic-metabolic cardiomyopathy induced by treatment with Na2HPO4, Sopolcort H, and adrenalin are studied. In the cardiac muscle cells that seem to be uninjured, by light-microscopic investigation considerable damages of the mitochondria, sarcoplasmatic reticulum, myofibrils and the intercalated discs are found. These damages show that the there are a heavy hypoxia and metabolic disturbances outside the infarcted zones. Probably, they have certain significance for the progression of the morbid process in the myocardium.

  3. Myocardial ischemic protection in natural mammalian hibernation.

    PubMed

    Yan, Lin; Kudej, Raymond K; Vatner, Dorothy E; Vatner, Stephen F

    2015-03-01

    Hibernating myocardium is an important clinical syndrome protecting the heart with chronic myocardial ischemia, named for its assumed resemblance to hibernating mammals in winter. However, the effects of myocardial ischemic protection have never been studied in true mammalian hibernation, which is a unique strategy for surviving extreme winter environmental stress. The goal of this investigation was to test the hypothesis that ischemic stress may also be protected in woodchucks as they hibernate in winter. Myocardial infarction was induced by coronary occlusion followed by reperfusion in naturally hibernating woodchucks in winter with and without hibernation and in summer, when not hibernating. The ischemic area at risk was similar among groups. Myocardial infarction was significantly less in woodchucks in winter, whether hibernating or not, compared with summer, and was similar to that resulting after ischemic preconditioning. Whereas several genes were up or downregulated in both hibernating woodchuck and with ischemic preconditioning, one mechanism was unique to hibernation, i.e., activation of cAMP-response element binding protein (CREB). When CREB was upregulated in summer, it induced protection similar to that observed in the woodchuck heart in winter. The cardioprotection in hibernation was also mediated by endothelial nitric oxide synthase, rather than inducible nitric oxide synthase. Thus, the hibernating woodchuck heart is a novel model to study cardioprotection for two major reasons: (1) powerful cardioprotection occurs naturally in winter months in the absence of any preconditioning stimuli, and (2) it resembles ischemic preconditioning, but with novel mechanisms, making this model potentially useful for clinical translation.

  4. Myocardial ischemic protection in natural mammalian hibernation

    PubMed Central

    Yan, Lin; Kudej, Raymond K.; Vatner, Dorothy E.

    2015-01-01

    Hibernating myocardium is an important clinical syndrome protecting the heart with chronic myocardial ischemia, named for its assumed resemblance to hibernating mammals in winter. However, the effects of myocardial ischemic protection have never been studied in true mammalian hibernation, which is a unique strategy for surviving extreme winter environmental stress. The goal of this investigation was to test the hypothesis that ischemic stress may also be protected in woodchucks as they hibernate in winter. Myocardial infarction was induced by coronary occlusion followed by reperfusion in naturally hibernating woodchucks in winter with and without hibernation and in summer, when not hibernating. The ischemic area at risk was similar among groups. Myocardial infarction was significantly less in woodchucks in winter, whether hibernating or not, compared with summer, and was similar to that resulting after ischemic preconditioning. Whereas several genes were up or downregulated in both hibernating woodchuck and with ischemic preconditioning, one mechanism was unique to hibernation, i.e., activation of cAMP-response element binding protein (CREB). When CREB was upregulated in summer, it induced protection similar to that observed in the woodchuck heart in winter. The cardioprotection in hibernation was also mediated by endothelial nitric oxide synthase, rather than inducible nitric oxide synthase. Thus, the hibernating woodchuck heart is a novel model to study cardioprotection for two major reasons: (1) powerful cardioprotection occurs naturally in winter months in the absence of any preconditioning stimuli, and (2) it resembles ischemic preconditioning, but with novel mechanisms, making this model potentially useful for clinical translation. PMID:25613166

  5. Concomitant canine distemper, infectious canine hepatitis, canine parvoviral enteritis, canine infectious tracheobronchitis, and toxoplasmosis in a puppy.

    PubMed

    Headley, Selwyn Arlington; Alfieri, Amauri Alcindo; Fritzen, Juliana Torres Tomazi; Garcia, João Luis; Weissenböck, Herbert; da Silva, Ana Paula; Bodnar, Livia; Okano, Werner; Alfieri, Alice Fernandes

    2013-01-01

    The concomitant infections of Canine distemper virus (CDV), Canine adenovirus A types 1 (CAdV-1) and 2 (CAdV-2), Canine parvovirus type 2 (CPV-2), and Toxoplasma gondii are described in a 43-day-old mixed-breed puppy. Clinically, there were convulsions and blindness with spontaneous death; 14 siblings of this puppy, born to a 10-month-old dam, which was seropositive (titer: 1,024) for T. gondii, also died. Necropsy revealed unilateral corneal edema (blue eye), depletion of intestinal lymphoid tissue, non-collapsible lungs, congestion of meningeal vessels, and a pale area in the myocardium. Histopathology demonstrated necrotizing myocarditis associated with intralesional apicomplexan protozoa; necrotizing and chronic hepatitis associated with rare intranuclear inclusion bodies within hepatocytes; necrotizing bronchitis and bronchiolitis; interstitial pneumonia associated with eosinophilic intracytoplasmic inclusion bodies within epithelial cells; atrophy and fusion of intestinal villi with cryptal necrosis; and white matter demyelination of the cerebrum and cerebellum associated with intranuclear inclusion bodies within astrocytes. Polymerase chain reaction (PCR) amplified the partial fragments (bp) of the CDV N gene (290 bp), CPV-2c VP2 capsid protein gene (583 bp), and CAdV-1 (508 bp) and CAdV-2 (1,030 bp) E gene from urine and tissue samples. The PCR assays demonstrated that the apicomplexan protozoa observed within several organs contained DNA specific for T. gondii; genotyping revealed T. gondii type III. The findings support the characterization of concomitant infections of CDV, CAdV-1, CAdV-2, CPV-2, and T. gondii in this puppy. Further, seroreactivity to T. gondii of the dam in association with the systemic disease observed in the puppy described herein is suggestive of congenital toxoplasmosis.

  6. Protective effect of methylprednisolone on ischaemic myocardium assessed by ventricular function.

    PubMed Central

    Krause, B L; Hassan, M A; McMilan, A B; Brown, A H

    1977-01-01

    Intracardiac surgical procedures are best carried out when the heart is still and bloodless. This condition, however, produces myocardial cellular damage with loss of contractility and compliance unless some protection can be provided. Myocardial contractility and compliance is best studied by isovolumic ventricular function tests, which were used to evaluate the protective effect of methylprednisolone on the isolated cross-perfused canine heart made ischaemic for 2 hours. Control experiments included 2 hours of ischaemia without methylprednisolone, and 2 hours of continuous normothermic cross-perfusion. The methylprednisolone-treated hearts had probably significantly better ventricular function after 2 hours of ischaemia than did hearts without the methylprednisolone, while the cross-perfused hearts were best overall. This work suggests that methylprednisolone may have a protective effect on the ischaemic myocardium of the intact canine heart. PMID:867332

  7. Canine lymphoma

    SciTech Connect

    Weller, R.E.

    1986-10-01

    Canine lymphoma has served as the ''workhorse'' for the development of veterinary oncology and as an important animal model for human non-Hodgkins lymphomas. Significant advances have been achieved in understanding the biological behavior of the disease and in its treatment. Although it is unlikely that a cure for lymphoma will be achieved, owners should be encouraged to treat their pets, provided they understand that only prolonged remissions and survivals are likely to result. Cooperative studies, employing large numbers of dogs, are needed to optimize and refine the classification scheme to provide a system with diagnostic and prognostic correlates and derive maximum benefit from therapeutic regimens. Such studies need to be prospective in nature, with a solid statistical base incorporated into their design. Rather than being content with what we have accomplished to date in treatment of canine lymphoma, the opportunity exists for the veterinary profession to make further significant contributions to the understanding and treatment of lymphoma in the dog. 10 refs., 4 tabs.

  8. The role of chemokines in mesenchymal stem cell homing to myocardium.

    PubMed

    Wu, Yaojiong; Zhao, Robert C H

    2012-03-01

    A growing body of preclinical evidence suggests that mesenchymal stem cells (MSCs) are effective for the structural and functional recovery of the infracted heart. Accordingly, clinical trials are underway to determine the benefit of MSC-based therapies. While systemic administration of MSCs is an attractive strategy, and is the route currently used for the administration of MSCs in clinical studies for myocardial infarction, the majority of infused cells do not appear to localize to infracted myocardium in animal studies. Recently, important progress has been made in identifying chemokine receptors critical for the migration and homing of MSCs. Here, we review recent literature regarding mechanisms of MSC homing and recruitment to the ischemic myocardium, and discuss potential influences of low engraftment rates of systemically administered MSCs to the infracted heart tissue on the effects of MSC-based therapies on myocardial infarction.

  9. Ischemic Colitis

    PubMed Central

    FitzGerald, James F.; Hernandez III, Luis O.

    2015-01-01

    Most clinicians associate ischemic colitis with elderly patients who have underlying cardiovascular comorbidities. While the majority of cases probably occur in this population, the disease can present in younger patients as a result of different risk factors, making the diagnosis challenging. While a majority of patients respond to medical management, surgery is required in approximately 20% of the cases and is associated with high morbidity and mortality. PMID:26034405

  10. Myocardial Ischemic Memory Imaging With Molecular Echocardiography

    PubMed Central

    Villanueva, Flordeliza S.; Lu, Erxiong; Bowry, Shivani; Kilic, Sevgi; Tom, Eric; Wang, Jianjun; Gretton, Joan; Pacella, John J.; Wagner, William R.

    2014-01-01

    Background Diagnosing acute coronary syndrome in patients presenting with chest discomfort is a challenge. Because acute myocardial ischemia/reperfusion is associated with endothelial upregulation of leukocyte adhesion molecules, which persist even after ischemia has resolved, we hypothesized that microbubbles designed to adhere to endothelial selectins would permit echocardiographic identification of recently ischemic myocardium. Methods and Results Lipid microbubbles (diameter, 3.3±1.7 μm) were synthesized. The selectin ligand sialyl Lewisx was conjugated to the microbubble surface (MBsLex). Control bubbles (MBCTL) bore surface Lewisx or sialyl Lewisc. Intravital microscopy of mouse cremaster muscle was performed after intravenous injection of MBsLex (n=11) or MBCTL (n=9) with or without prior intrascrotal tumor necrosis factor–α. There was greater adhesion of MBsLex to inflamed versus noninflamed endothelium (P=0.0081). Rats (n=12) underwent 15 minutes of anterior descending coronary artery occlusion. After 30 minutes and 1 hour of reperfusion, high-mechanical-index nonlinear echocardiographic imaging was performed in which single frames were acquired at 3.5 and 4 minutes after intravenous injection of MBsLex or MBCTL. Video intensity at 4 minutes was subtracted from that at 3.5 minutes to derive target-specific acoustic signal. MBsLex caused greater opacification in postischemic versus nonischemic myocardium at both time points (P≤0.002). Immunostaining confirmed endothelial P-selectin expression in the ischemic bed. Conclusions Echocardiographic identification of recently ischemic myocardium is possible using ultrasound contrast agents targeted to selectins. This may offer a new approach to the more timely and precise diagnosis of acute coronary syndrome in patients presenting with chest pain of uncertain cardiac origin. PMID:17210843

  11. Signal transduction and Ca2+ signaling in contractile regulation induced by crosstalk between endothelin-1 and norepinephrine in dog ventricular myocardium.

    PubMed

    Chu, Li; Takahashi, Reiko; Norota, Ikuo; Miyamoto, Takuya; Takeishi, Yasuchika; Ishii, Kuniaki; Kubota, Isao; Endoh, Masao

    2003-05-16

    In certain cardiovascular disorders, such as congestive heart failure and ischemic heart disease, several endogenous regulators, including norepinephrine (NE) and endothelin-1 (ET-1), are released from various types of cell. Because plasma levels of these regulators are elevated, it seems likely that cardiac contraction might be regulated by crosstalk among these endogenous regulators. We studied the regulation of cardiac contractile function by crosstalk between ET-1 and NE and its relationship to Ca2+ signaling in canine ventricular myocardium. ET-1 alone did not affect the contractile function. However, in the presence of NE at subthreshold concentrations (0.1 to 1 nmol/L), ET-1 had a positive inotropic effect (PIE). In the presence of NE at higher concentrations (100 to 1000 nmol/L), ET-1 had a negative inotropic effect. ET-1 had a biphasic inotropic effect in the presence of NE at an intermediate concentration (10 nmol/L). The PIE of ET-1 was associated with an increase in myofilament sensitivity to Ca2+ ions and a small increase in Ca2+ transients, which required the simultaneous activation of protein kinase A (PKA) and PKC. ET-1 elicited translocation of PKCepsilon from cytosolic to membranous fraction, which was inhibited by the PKC inhibitor GF 109203X. Whereas the Na+-H+ exchange inhibitor Hoe 642 suppressed partially the PIE of ET-1, detectable alteration of pHi did not occur during application of ET-1 and NE. The negative inotropic effect of ET-1 was associated with a pronounced decrease in Ca2+ transients, which was mediated by pertussis toxin-sensitive G proteins, activation of protein kinase G, and phosphatases. When the inhibitory pathway was suppressed, ET-1 had a PIE even in the absence of NE. Our results indicate that the myocardial contractility is regulated either positively or negatively by crosstalk between ET-1 and NE through different signaling pathways whose activation depends on the concentration of NE in the dog.

  12. Characterization of pericardial and plasma ghrelin levels in patients with ischemic and non-ischemic heart disease.

    PubMed

    Sax, Balazs; Merkely, Béla; Túri, Katalin; Nagy, Andrea; Ahres, Abdelkrim; Hartyánszky, István; Hüttl, Tivadar; Szabolcs, Zoltán; Cseh, Károly; Kékesi, Violetta

    2013-09-10

    Ghrelin is an endocrine regulatory peptide with multiple functions including cardioprotective effects. It is produced in various tissues among others in the myocardium. Pericardial fluid has been proven to be a biologically active compartment of the heart that communicates with the myocardial interstitium. Thus, pericardial level of certain agents may reflect their concentration in the myocardium well. In our study we measured acylated (active) and total (acylated and non-acylated) pericardial and plasma ghrelin levels of patients with ischemic and non-ischemic heart disease. Pericardial fluid and plasma samples were obtained from patients with coronary artery disease (ISCH, n=54) or valvular heart disease (VHD, n=41) undergoing cardiac surgery. Acylated pericardial ghrelin concentrations were found to be significantly higher in patients with ischemic heart disease (ISCH vs. VHD, 32±3 vs. 16±2pg/ml, p<0.01), whereas plasma levels of the peptide showed no difference between patient groups. Pericardial-to-plasma ratio, an index abolishing systemic effects on local ghrelin level was also significantly higher in ISCH group for both acylated and total ghrelin. Plasma total ghrelin showed negative correlation to BMI, plasma insulin and insulin resistance index HOMA-A. Pericardial acylated and total ghrelin concentrations were negatively correlated with posterior wall thickness (R=-0.31, p<0.05 and R=-0.35, p<0.01, respectively). Plasma insulin concentration and HOMA-A showed significant negative correlation with pericardial ghrelin levels. In conclusion, increased pericardial active ghrelin content and higher pericardial-to-plasma ghrelin ratio were found in ischemic heart disease as compared to non-ischemic patients suggesting an increased ghrelin production of the chronically ischemic myocardium. According to our results, pericardial ghrelin content is negatively influenced by left ventricular hypertrophy and insulin resistance.

  13. Contrast-enhanced magnetic resonance imaging of hypoperfused myocardium.

    PubMed

    Schaefer, S; Lange, R A; Gutekunst, D P; Parkey, R W; Willerson, J T; Peshock, R M

    1991-06-01

    Contrast-enhanced magnetic resonance (MR) imaging can define myocardial perfusion defects due to acute coronary occlusion. However, since most clinically important diagnostic examinations involve coronary arteries with subtotal stenoses, we investigated the ability of MR imaging with a manganese contrast agent to detect perfusion abnormalities in a canine model of partial coronary artery stenosis. The contrast agent was administered after the creation of a partial coronary artery stenosis with the addition of the coronary vasodilator dipyridamole in six of 12 animals. The hearts were imaged ex situ using gradient reversal and spin-echo sequences, and images were analyzed to determine differences in signal intensity between hypoperfused and normally perfused myocardium. Comparison of MR images with regional blood flow and thallium-201 measurements showed good concordance of hypoperfused segments in those animals given dipyridamole, with 75% of the abnormal segments correctly identified. In those animals not given dipyridamole, 48% of segments were correctly identified. Thus, ex vivo MR imaging with a paramagnetic contrast enhancement can be used to detect acute regional myocardial perfusion abnormalities due to severe partial coronary artery stenoses.

  14. Effect of glutathion pretreatment on hypothermic ischemic cardioplegia.

    PubMed

    Amano, J; Sunamori, M; Okamura, T; Suzuki, A

    1982-01-01

    Glutathion (GSH) plays an important role in maintenance of the redox state of the myocardium and acts as the membrane stabilizer. Seventeen patients who underwent cardiac surgery were subjected to cardiopulmonary bypass (CPB) and ischemic cardioplegia. The effect of GSH on ischemic myocardium was evaluated by serum lysosomal enzymes (acid phosphatase, beta-glucuronidase), isoenzymes of creatine phosphokinase (MB-CPK) and aspartate aminotransferase (m-GOT). standard CPB was instituted and systemic hypothermia was employed. GSH was administered to 8 patients in a dose of 200 mg/kg i.v. prior to institution of CPB. Mixed venous blood was sampled before administration of GSH, 10 min after institution of CPB and 0, 1, 6, 24 and 48 hr of reperfusion period following cardioplegia. Activity of acid phosphatase and beta-glucuronidase were significantly suppressed in the GSH-treated group compared to the non-treated group at 24 hours of reperfusion and immediately after aortic unclamping, respectively. Serum MB-CPK levels remained stable during reperfusion, but in the non-treated group, the level increased significantly at 6 hours of reperfusion. Increment of serum m-GOT levels was significantly suppressed at 1, 6 and 24 hours of reperfusion, compared to the non-treated group. These data suggest that pretreatment of GSH can protect the myocardium subjected to CPB from ischemic insult.

  15. Anisotropic Elastography for Local Passive Properties and Active Contractility of Myocardium from Dynamic Heart Imaging Sequence

    PubMed Central

    Wang, Ge; Sun, L. Z.

    2006-01-01

    Major heart diseases such as ischemia and hypertrophic myocardiopathy are accompanied with significant changes in the passive mechanical properties and active contractility of myocardium. Identification of these changes helps diagnose heart diseases, monitor therapy, and design surgery. A dynamic cardiac elastography (DCE) framework is developed to assess the anisotropic viscoelastic passive properties and active contractility of myocardial tissues, based on the chamber pressure and dynamic displacement measured with cardiac imaging techniques. A dynamic adjoint method is derived to enhance the numerical efficiency and stability of DCE. Model-based simulations are conducted using a numerical left ventricle (LV) phantom with an ischemic region. The passive material parameters of normal and ischemic tissues are identified during LV rapid/reduced filling and artery contraction, and those of active contractility are quantified during isovolumetric contraction and rapid/reduced ejection. It is found that quasistatic simplification in the previous cardiac elastography studies may yield inaccurate material parameters. PMID:23165032

  16. Anisotropic elastography for local passive properties and active contractility of myocardium from dynamic heart imaging sequence.

    PubMed

    Liu, Yi; Wang, Ge; Sun, L Z

    2006-01-01

    Major heart diseases such as ischemia and hypertrophic myocardiopathy are accompanied with significant changes in the passive mechanical properties and active contractility of myocardium. Identification of these changes helps diagnose heart diseases, monitor therapy, and design surgery. A dynamic cardiac elastography (DCE) framework is developed to assess the anisotropic viscoelastic passive properties and active contractility of myocardial tissues, based on the chamber pressure and dynamic displacement measured with cardiac imaging techniques. A dynamic adjoint method is derived to enhance the numerical efficiency and stability of DCE. Model-based simulations are conducted using a numerical left ventricle (LV) phantom with an ischemic region. The passive material parameters of normal and ischemic tissues are identified during LV rapid/reduced filling and artery contraction, and those of active contractility are quantified during isovolumetric contraction and rapid/reduced ejection. It is found that quasistatic simplification in the previous cardiac elastography studies may yield inaccurate material parameters.

  17. Canine thymoma.

    PubMed

    Aronsohn, M

    1985-07-01

    Thymoma is an uncommon canine neoplasm of thymic epithelial cells. It is seen in various breeds but may occur more frequently in German Shepherd Dogs. Middle-aged or older dogs can be affected and no sex predilection exists. A paraneoplastic syndrome of myasthenia gravis, nonthymic malignant tumors, and/or polymyositis occurs in a significant number of dogs with thymoma. Clinical signs are variable and are related to a space-occupying cranial mediastinal mass and/or manifestations of the paraneo-plastic syndrome. Dyspnea is the most common presenting clinical sign. Thoracic radiographs usually show a cranial mediastinal mass. Lymphoma is the main differential diagnosis. A definitive diagnosis may be made by closed biopsy but is more likely to be confirmed by thoracotomy. Thymomas may be completely contained within the thymic capsule or may spread by local invasion or metastasis. A staging system allows for an accurate prognosis and a therapeutic plan. Surgical removal of encapsulated thymomas may result in long-term survival or cure. Invasive or metastatic thymomas carry a guarded prognosis. Manifestations of the paraneoplastic syndrome complicate treatment. Adjuvant radiation and chemotherapy may be of value for advanced cases; however, adequate clinical trials have not been done in the dog.

  18. Neurogenic stunned myocardium in subarachnoid hemorrhage.

    PubMed

    Kerro, Ali; Woods, Timothy; Chang, Jason J

    2017-04-01

    "Stunned myocardium," characterized by reversible left ventricular dysfunction, was first described via animal models using transient coronary artery occlusion. However, this phenomenon has also been noted with neurologic pathologies and collectively been labeled "neurogenic stunned myocardium" (NSM). Neurogenic stunned myocardium resulting from subarachnoid hemorrhage (SAH) is a challenging pathology due to its diagnostic uncertainty. Traditional diagnostic criteria for NSM after SAH focus on electrocardiographic and echocardiographic abnormalities and troponemia. However, tremendous heterogeneity still exists. Traditional pathophysiological mechanisms for NSM encompassed hypothalamic and myocardial perivascular lesions. More recently, research on pathophysiology has centered on myocardial microvascular dysfunction and genetic polymorphisms. Catecholamine surging as a mechanism has also gained attention with particular focus placed on the role of adrenergic blockade in both the prehospital and acute settings. Management remains largely supportive with case reports acknowledging the utility of inotropes such as dobutamine and milrinone and intra-aortic balloon pump when NSM is accompanied by cardiogenic shock. Neurogenic stunned myocardium that follows SAH can result in many complications such as arrhythmias, pulmonary edema, and prolonged intubation, which can negatively impact long-term recovery from SAH and increase morbidity and mortality. This necessitates the need to accurately diagnose and treat NSM.

  19. Myocardium wall thickness transducer and measuring method

    NASA Technical Reports Server (NTRS)

    Feldstein, C.; Lewis, G. W.; Silver, R. H.; Culler, V. H. (Inventor)

    1976-01-01

    A miniature transducer for measuring changes of thickness of the myocardium is described. The device is easily implantable without traumatizing the subject, without affecting the normal muscle behavior, and is removable and implantable at a different muscle location. Operating features of the device are described.

  20. Neurogenic pathways in remote ischemic preconditioning induced cardioprotection: Evidences and possible mechanisms

    PubMed Central

    Aulakh, Amritpal Singh; Randhawa, Puneet Kaur; Singh, Nirmal

    2017-01-01

    Remote ischemic preconditioning (RIPC) is an intrinsic phenomenon whereby 3~4 consecutive ischemia-reperfusion cycles to a remote tissue (noncardiac) increases the tolerance of the myocardium to sustained ischemiareperfusion induced injury. Remote ischemic preconditioning induces the local release of chemical mediators which activate the sensory nerve endings to convey signals to the brain. The latter consequently stimulates the efferent nerve endings innervating the myocardium to induce cardioprotection. Indeed, RIPC-induced cardioprotective effects are reliant on the presence of intact neuronal pathways, which has been confirmed using nerve resection of nerves including femoral nerve, vagus nerve, and sciatic nerve. The involvement of neurogenic signaling has been further substantiated using various pharmacological modulators including hexamethonium and trimetaphan. The present review focuses on the potential involvement of neurogenic pathways in mediating remote ischemic preconditioning-induced cardioprotection. PMID:28280407

  1. The potential for nanotechnology to improve delivery of therapy to the acute ischemic heart.

    PubMed

    Evans, Cameron W; Iyer, K Swaminathan; Hool, Livia C

    2016-04-01

    Treatment of acute cardiac ischemia remains an area in which there are opportunities for therapeutic improvement. Despite significant advances, many patients still progress to cardiac hypertrophy and heart failure. Timely reperfusion is critical in rescuing vulnerable ischemic tissue and is directly related to patient outcome, but reperfusion of the ischemic myocardium also contributes to damage. Overproduction of reactive oxygen species, initiation of an inflammatory response and deregulation of calcium homeostasis all contribute to injury, and difficulties in delivering a sufficient quantity of drug to the affected tissue in a controlled manner is a limitation of current therapies. Nanotechnology may offer significant improvements in this respect. Here, we review recent examples of how nanoparticles can be used to improve delivery to the ischemic myocardium, and suggest some approaches that may lead to improved therapies for acute cardiac ischemia.

  2. Localization of Impacted Canines

    PubMed Central

    Mehrotra, Praveen; Bhagchandani, Jitendra; Singh, Ashish; Garg, Aarti; Kumar, Snehi; Sharma, Ashish; Yadav, Harsh

    2015-01-01

    Impaction of maxillary canines is a frequently encountered clinical problem. The impaction of canine can be prevented in some situationsif the canine displacement is diagnosed in the early mixed dentition period and this would be extremely useful for the clinician. Hence,it is very important to focus on the means of early diagnosis and interception of this clinical situation. In the present article, the differentmodalities used to diagnose the impacted canine are reviewed with an insight into current 3-D modalities. PMID:25738100

  3. Collateral circulation as a marker of the presence of viable myocardium in patients with recent myocardial infarction

    SciTech Connect

    Fujita, M.; Ohno, A.; Wada, O.; Miwa, K.; Nozawa, T.; Yamanishi, K.; Sasayama, S. )

    1991-08-01

    The relationship between the presence of viable myocardium and the extent of coronary collateral circulation to the infarct area was evaluated in 20 patients with a recent anterior myocardial infarction who had complete obstruction of the left anterior descending coronary artery. The viability of myocardial tissue was assessed by exercise thallium-201 myocardial scintigraphy, and the collateral circulation was angiographically evaluated by means of a collateral index ranging from 0 to 3. Patients were divided into two groups according to the presence (group 1, n = 10) or absence (group 2, n = 10) of viable myocardium in the perfusion territory of the infarct-related artery. The collateral index in group 1 was 2.5 {plus minus} 0.5 (SD), which was significantly higher than the 0.7 {plus minus} 0.8 in group 2. These findings indicate that the presence of ischemic but viable myocardium is intimately related to the development of collateral circulation in patients with myocardial infarction, and the existence of well-developed collateral channels predicts the presence of viable myocardium in the infarct area.

  4. Contribution of myocardium hydraulic skeleton to left ventricular wall interaction and synergy in dogs.

    PubMed

    Barra, Juan Gabriel; Crottogini, Alberto José; Willshaw, Peter; Lascano, Elena Catalina; Pichel, Ricardo Horacio

    2004-08-01

    The most premature motion change after coronary occlusion is early diastolic thinning of the ischemic left ventricular (LV) wall, with concomitant thickening of the normoperfused wall. We aimed 1). to demonstrate that these early changes are the result of the absence of fluid within the ischemic myocardium (hydraulic skeleton) rather than to cell anoxia and 2). to quantitate the contribution of the lack of hydraulic skeleton to left ventricular asynergy of contraction in seven anesthetized dogs submitted to acute, short-lasting circumflex artery (Cx) occlusion (ischemia) and to perfusion of the Cx with an oxygen-free solution (anoxia). We analyzed the time course of regional work index (WI, area of the LV pressure-wall thickness loop) and regional efficiency (defined as the ratio of WI to the maximum possible work). Interwall asynergy was defined as the difference between the regional efficiency of the anterior and posterior walls. After 9-10 s, posterior wall efficiency decreased 37 +/- 6% with anoxia and 72 +/- 3% with ischemia (P < 0.025), and interwall asynergy was 0 +/- 6% with anoxia and 32 +/- 5% with ischemia (P < 0.05). The contribution of absent hydraulic skeleton to interwall asynergy (calculated as the difference between %asynergy in anoxia and %asynergy in ischemia) was 30 +/- 8% (P < 0.05). In conclusion, the earliest wall motion change observed after acute coronary occlusion, namely ischemic wall thinning concomitant with normoperfused wall thickening during isovolumic relaxation, is the result of the absence of intracoronary fluid. The lack of hydraulic skeleton within the myocardium contributes approximately 30% to interwall asynergy.

  5. Identification of Angiogenesis Rich-Viable Myocardium using RGD Dimer based SPECT after Myocardial Infarction

    PubMed Central

    Lee, Min Su; Park, Hyun Soo; Lee, Byung Chul; Jung, Jae Ho; Yoo, Jung Sun; Kim, Sang Eun

    2016-01-01

    Cardiac healing after myocardial ischemia is a complex biological process. Advances in understanding of wound healing response have paved the way for clinical testing of novel molecular imaging to improve clinical outcomes. A key factor for assessing myocardial viability after ischemic injury is the evaluation of angiogenesis accompanying increased expression of integrin αvβ3. Here, we describe the capability of an αvβ3 integrin-targeting SPECT agent, 99mTc-IDA-D-[c(RGDfK)]2, for identification of ischemic but viable myocardium, i.e., hibernating myocardium which is crucial to predict functional recovery after revascularization, the standard care of cardiovascular medicine. In vivo SPECT imaging of rat models with transient coronary occlusion showed significantly high uptake of 99mTc-IDA-D-[c(RGDfK)]2 in the ischemic region. Comparative measurements with 201Tl SPECT and 18F-FDG PET, then, proved that such prominent uptake of 99mTc-IDA-D-[c(RGDfK)]2 exactly matched the hallmark of hibernation, i.e., the perfusion-metabolism mismatch pattern. The uptake of 99mTc-IDA-D-[c(RGDfK)]2 was non-inferior to that of 18F-FDG, confirmed by time-course variation analysis. Immunohistochemical characterization revealed that an intense signal of 99mTc-IDA-D-[c(RGDfK)]2 corresponded to the vibrant angiogenic events with elevated expression of αvβ3 integrin. Together, these results establish that 99mTc-IDA-D-[c(RGDfK)]2 SPECT can serve as a sensitive clinical measure for myocardial salvage to identify the patients who might benefit most from revascularization. PMID:27283041

  6. Ischemic Strokes (Clots)

    MedlinePlus

    ... Quiz 5 Things to Know About Stroke Ischemic Strokes (Clots) Updated:Nov 9,2016 Ischemic stroke accounts ... strokes. Read more about silent strokes . TIA and Stroke: Medical Emergencies When someone has shown symptoms of ...

  7. Vegfa Impacts Early Myocardium Development in Zebrafish

    PubMed Central

    Zhu, Diqi; Fang, Yabo; Gao, Kun; Shen, Jie; Zhong, Tao P.; Li, Fen

    2017-01-01

    Vascular endothelial growth factor A (Vegfa) signaling regulates cardiovascular development. However, the cellular mechanisms of Vegfa signaling in early cardiogenesis remain poorly understood. The present study aimed to understand the differential functions and mechanisms of Vegfa signaling in cardiac development. A loss-of-function approach was utilized to study the effect of Vegfa signaling in cardiogenesis. Both morphants and mutants for vegfaa display defects in cardiac looping and chamber formation, especially the ventricle. Vegfa regulates the heart morphogenesis in a dose-dependent manner. Furthermore, the initial fusion of the bilateral myocardium population is delayed rather than endocardium. The results demonstrate that Vegfa signaling plays a direct impact on myocardium fusion, indicating that it is the initial cause of the heart defects. The heart morphogenesis is regulated by Vegfa in a dose-dependent manner, and later endocardium defects may be secondary to impaired myocardium–endocardium crosstalk. PMID:28230770

  8. Automatic cardiac MRI myocardium segmentation using graphcut

    NASA Astrophysics Data System (ADS)

    Kedenburg, Gunnar; Cocosco, Chris A.; Köthe, Ullrich; Niessen, Wiro J.; Vonken, Evert-jan P. A.; Viergever, Max A.

    2006-03-01

    Segmentation of the left myocardium in four-dimensional (space-time) cardiac MRI data sets is a prerequisite of many diagnostic tasks. We propose a fully automatic method based on global minimization of an energy functional by means of the graphcut algorithm. Starting from automatically obtained segmentations of the left and right ventricles and a cardiac region of interest, a spatial model is constructed using simple and plausible assumptions. This model is used to learn the appearance of different tissue types by non parametric robust estimation. Our method does not require previously trained shape or appearance models. Processing takes 30-40s on current hardware. We evaluated our method on 11 clinical cardiac MRI data sets acquired using cine balanced fast field echo. Linear regression of the automatically segmented myocardium volume against manual segmentations (performed by a radiologist) showed an RMS error of about 12ml.

  9. Mechanisms of myocardium-coronary vessel interaction

    PubMed Central

    Algranati, Dotan; Kassab, Ghassan S.

    2010-01-01

    The mechanisms by which the contracting myocardium exerts extravascular forces (intramyocardial pressure, IMP) on coronary blood vessels and by which it affects the coronary flow remain incompletely understood. Several myocardium-vessel interaction (MVI) mechanisms have been proposed, but none can account for all the major flow features. In the present study, we hypothesized that only a specific combination of MVI mechanisms can account for all observed coronary flow features. Three basic interaction mechanisms (time-varying elasticity, myocardial shortening-induced intracellular pressure, and ventricular cavity-induced extracellular pressure) and their combinations were analyzed based on physical principles (conservation of mass and force equilibrium) in a realistic data-based vascular network. Mechanical properties of both vessel wall and myocardium were coupled through stress analysis to simulate the response of vessels to internal blood pressure and external (myocardial) mechanical loading. Predictions of transmural dynamic vascular pressure, diameter, and flow velocity were determined under each MVI mechanism and compared with reported data. The results show that none of the three basic mechanisms alone can account for the measured data. Only the combined effect of the cavity-induced extracellular pressure and the shortening-induced intramyocyte pressure provides good agreement with the majority of measurements. These findings have important implications for elucidating the physical basis of IMP and for understanding coronary phasic flow and coronary artery and microcirculatory disease. PMID:19966048

  10. Backscatter and attenuation characterization of ventricular myocardium

    NASA Astrophysics Data System (ADS)

    Gibson, Allyson Ann

    2009-12-01

    This Dissertation presents quantitative ultrasonic measurements of the myocardium in fetal hearts and adult human hearts with the goal of studying the physics of sound waves incident upon anisotropic and inhomogeneous materials. Ultrasound has been used as a clinical tool to assess heart structure and function for several decades. The clinical usefulness of this noninvasive approach has grown with our understanding of the physical mechanisms underlying the interaction of ultrasonic waves with the myocardium. In this Dissertation, integrated backscatter and attenuation analyses were performed on midgestational fetal hearts to assess potential differences in the left and right ventricular myocardium. The hearts were interrogated using a 50 MHz transducer that enabled finer spatial resolution than could be achieved at more typical clinical frequencies. Ultrasonic data analyses demonstrated different patterns and relative levels of backscatter and attenuation from the myocardium of the left ventricle and the right ventricle. Ultrasonic data of adult human hearts were acquired with a clinical imaging system and quantified by their magnitude and time delay of cyclic variation of myocardial backscatter. The results were analyzing using Bayes Classification and ROC analysis to quantify potential advantages of using a combination of two features of cyclic variation of myocardial backscatter over using only one or the other feature to distinguish between groups of subjects. When the subjects were classified based on hemoglobin A1c, the homeostasis model assessment of insulin resistance, and the ratio of triglyceride to high-density lipoprotein-cholesterol, differences in the magnitude and normalized time delay of cyclic variation of myocardial backscatter were observed. The cyclic variation results also suggested a trend toward a larger area under the ROC curve when information from magnitude and time delay of cyclic variation is combined using Bayes classification than when

  11. Acute ischemic preconditioning of skeletal muscle prior to flap elevation augments muscle-flap survival.

    PubMed

    Carroll, C M; Carroll, S M; Overgoor, M L; Tobin, G; Barker, J H

    1997-07-01

    Ischemic preconditioning of the myocardium with repeated brief periods of ischemia and reperfusion prior to prolonged ischemia significantly reduces subsequent myocardial infarction. Following ischemic preconditioning, two "windows of opportunity" (early and late) exist, during which time prolonged ischemia can occur with reduced infarction size. The early window occurs at approximately 4 hours and the late window at 24 hours following ischemic preconditioning of the myocardium. We investigated if ischemic preconditioning of skeletal muscle prior to flap creation improved subsequent flap survival and perfusion immediately or 24 hours following ischemic preconditioning. Currently, no data exist on the utilization of ischemic preconditioning in this fashion. The animal model used was the latissimus dorsi muscle of adult male Sprague-Dawley rats. Animals were assigned to three groups, and the right or left latissimus dorsi muscle was chosen randomly in each animal. Group 1 (n = 12) was the control group, in which the entire latissimus dorsi muscle was elevated acutely without ischemic preconditioning. Group 2 (n = 8) investigated the effects of ischemic preconditioning in the early window. In this group, the latissimus dorsi muscle was elevated immediately following preconditioning. Group 3 (n = 8) investigated the effects of ischemic preconditioning in the late window, with elevation of the latissimus dorsi muscle 24 hours following ischemic preconditioning. The preconditioning regimen used in groups 2 and 3 was two 30-minute episodes of normothermic global ischemia with intervening 10-minute episodes of reperfusion. Latissimus dorsi muscle ischemia was created by occlusion of the thoracodorsal artery and vein and the intercostal perforators, after isolation of the muscle on these vessels. Muscle perfusion was assessed by a laser-Doppler perfusion imager. One week after flap elevation, muscle necrosis was quantified in all groups by means of computer-assisted digital

  12. Prolonged Cardiac Dysfunction After Intraparenchymal Hemorrhage and Neurogenic Stunned Myocardium

    PubMed Central

    Krishnamoorthy, Vijay; Wilson, Thomas; Sharma, Deepak; Vavilala, Monica S.

    2015-01-01

    Cardiac dysfunction occurring secondary to neurologic disease, termed neurogenic stunned myocardium, is an incompletely understood phenomenon that has been described after several distinct neurologic processes. We present a case of neurogenic stunned myocardium, discovered intraoperatively after anesthetic induction, in a patient who presented to our operating room with a recent intraparenchymal hemorrhage. We discuss the longitudinal cardiac functional course after neurogenic stunned myocardium. Lastly, we discuss the pathophysiology of neurogenic stunned myocardium, as well as its implications for anesthesiologists caring for neurosurgical patients. PMID:26462162

  13. Metastatic Midgut Carcinoid in the Myocardium.

    PubMed

    Bukowczan, Jakub; Lois, Konstantinos B; Skinner, Jane; Petrides, George; James, Robert Andrew; Perros, Petros

    2015-09-01

    Metastasis of neuroendocrine tumor to the myocardium is rare. We present a case of 64-year-old woman, who presented initially with abdominal pain and large adnexal mass. The image-guided biopsy showed low-grade neuroendocrine tumor with Ki67 less than 2% within the ovarian tissue. CT staging revealed bilateral adnexal masses, liver metastases, and primary lesion in the terminal ileum. Octreoscan showed marked tracer uptake within the lower esophagus not related to obvious mass on CT scan; the echocardiography confirmed the presence of a 2.7 cm LV/LA mass. In this case, close correlation between ECHO and the octreoscan obviated need for myocardial biopsy.

  14. Canine hearing loss management.

    PubMed

    Scheifele, Lesa; Clark, John Greer; Scheifele, Peter M

    2012-11-01

    Dog owners and handlers are naturally concerned when suspicion of hearing loss arises for their dogs. Questions frequently asked of the veterinarian center on warning signs of canine hearing loss and what can be done for the dog if hearing loss is confirmed. This article addresses warning signs of canine hearing loss, communication training and safety awareness issues, and the feasibility of hearing aid amplification for dogs.

  15. Leukocytes Link Local and Systemic Inflammation in Ischemic Cardiovascular Disease: An Expanded “Cardiovascular Continuum”

    PubMed Central

    Libby, Peter; Nahrendorf, Matthias; Swirski, Filip K.

    2016-01-01

    We have traditionally viewed ischemic heart disease in a cardiocentric manner: plaques grow in arteries until they block blood flow, causing acute coronary and other ischemic syndromes. Recent research provides new insight into the integrative biology of inflammation as it contributes to ischemic cardiovascular disease. These results have revealed hitherto unsuspected inflammatory signaling networks at work in these disorders that link the brain, autonomic nervous system, bone marrow, and spleen to the atherosclerotic plaque and to the infarcting myocardium. A burgeoning clinical literature indicates that such inflammatory networks—far from a mere laboratory curiosity—operate in our patients and can influence aspects of ischemic cardiovascular disease that determine decisively clinical outcomes. These new findings enlarge the circle of the traditional “cardiovascular continuum” beyond the heart and vessels to include the nervous system, the spleen, and the bone marrow. PMID:26940931

  16. Magnetic Resonance Imaging of Non-ischemic Cardiomyopathies: A Pictorial Essay.

    PubMed

    Olivas-Chacon, Cristina I; Mullins, Carola; Stewart, Kevan; Akle, Nassim; Calleros, Jesus E; Ramos-Duran, Luis R

    2015-01-01

    Non-ischemic cardiomyopathies are defined as either primary or secondary diseases of the myocardium resulting in cardiac dysfunction. While primary cardiomyopathies are confined to the heart and can be genetic or acquired, secondary cardiomyopathies show involvement of the heart as a manifestation of an underlying systemic disease including metabolic, inflammatory, granulomatous, infectious, or autoimmune entities. Non-ischemic cardiomyopathies are currently classified as hypertrophic, dilated, restrictive, or unclassifiable, including left ventricular non-compaction. Cardiovascular Magnetic Resonance Imaging (CMRI) not only has the capability to assess cardiac morphology and function, but also the ability to detect edema, hemorrhage, fibrosis, and intramyocardial deposits, providing a valuable imaging tool in the characterization of non-ischemic cardiomyopathies. This pictorial essay shows some of the most important non-ischemic cardiomyopathies with an emphasis on magnetic resonance imaging features.

  17. Magnetic Resonance Imaging of Non-ischemic Cardiomyopathies: A Pictorial Essay

    PubMed Central

    Olivas-Chacon, Cristina I; Mullins, Carola; Stewart, Kevan; Akle, Nassim; Calleros, Jesus E; Ramos-Duran, Luis R

    2015-01-01

    Non-ischemic cardiomyopathies are defined as either primary or secondary diseases of the myocardium resulting in cardiac dysfunction. While primary cardiomyopathies are confined to the heart and can be genetic or acquired, secondary cardiomyopathies show involvement of the heart as a manifestation of an underlying systemic disease including metabolic, inflammatory, granulomatous, infectious, or autoimmune entities. Non-ischemic cardiomyopathies are currently classified as hypertrophic, dilated, restrictive, or unclassifiable, including left ventricular non-compaction. Cardiovascular Magnetic Resonance Imaging (CMRI) not only has the capability to assess cardiac morphology and function, but also the ability to detect edema, hemorrhage, fibrosis, and intramyocardial deposits, providing a valuable imaging tool in the characterization of non-ischemic cardiomyopathies. This pictorial essay shows some of the most important non-ischemic cardiomyopathies with an emphasis on magnetic resonance imaging features. PMID:26199786

  18. Uptake of iodinated contrast material by the ischemically damaged myocardial cell.

    PubMed

    Newell, J D; Higgins, C B; Abraham, J L

    1982-01-01

    Computerized transmission tomography has shown differential contrast enhancement of the area of ischemic damage after intravenous administration of iodinated contrast material. The current study performed in normal dogs and dogs with two-day-old and 30-day-old myocardial infarctions was intended to determine if the iodine accumulation is intracellular. Scanning electron microscopy with energy dispersive x-ray analysis detected iodine peaks associated with the cells in areas of ischemic damage, while iodine peaks were not detected in normal myocardium. Energy spectra in the area of ischemic damage showed a significant increase in the Na+ -K+ ratio compared to normal myocardium, consistent with the loss of cellular membrane integrity in this region. Results were similar for both two- and 30-day-old infarcts. These results indicate that iodinated contrast material attaches to the membrane of enters the ischemically damaged cell, but is virtually excluded from the normal myocardial cell. It may serve as a marker of myocardial cells which have lost cellular membrane integrity after an ischemic insult.

  19. Ischemic preconditioning. Experimental facts and clinical perspective.

    PubMed

    Post, H; Heusch, G

    2002-12-01

    Brief periods of non-lethal ischemia and reperfusion render the myocardium more resistant to subsequent ischemia. This adaption occurs in a biphasic pattern: the first being active immediately and lasting for 2-3 hrs (early preconditioning), the second starting at 24 hrs until 72 hrs after the initial ischemia (delayed preconditioning) and requiring genomic activation with de novo protein synthesis. Early preconditioning is more potent than delayed preconditioning in reducing infarct size; delayed preconditioning also attenuates myocardial stunning. Early preconditioning depends on the ischemia-induced release of adenosine and opioids and, to a lesser degree, also bradykinin and prostaglandins. These molecules activate G-protein coupled receptors, initiate the activation of KATP channels and generation of oxygen radicals, and stimulate a series of protein kinases with essential roles for protein kinase C, tyrosine kinases and members of the MAP kinase family. Delayed preconditioning is triggered by a similar sequence of events, but in addition essentially depends on eNOS-derived NO. Both early and pharmacological preconditioning can be pharmacologically mimicked by exogenous adenosine, opioids, NO and activators of protein kinase C. Newly synthetized proteins associated with delayed preconditioning comprise iNOS, COX-2, manganese superoxide dismutase and possibly heat shock proteins. The final mechanism of protection by preconditioning is yet unknown; energy metabolism, KATP channels, the sodium-proton exchanger, stabilisation of the cytoskeleton and volume regulation will be discussed. For ethical reasons, evidence for ischemic preconditioning in humans is hard to provide. Clinical findings that parallel experimental ischemic preconditioning are reduced ST-segment elevation and pain during repetitive PTCA or exercise tests, a better prognosis of patients in whom myocardial infarction was preceded by angina, and reduced serum markers of myocardial necrosis after

  20. OCT imaging of myocardium extending to pulmonary vein

    NASA Astrophysics Data System (ADS)

    Li, Zhifang; Dickfeld, Timm; Tang, Qinggong; Wang, Bohan; Chen, Yu

    2016-02-01

    In this study, we propose to use optical coherence tomography to enable a direct visualization of myocardium extending into the pulmonary vein (PV). The results showed that there are obvious differences in the morphology of myocardium and fibrous tissue in the transition region of myocardial sleeve, which is in agreement with the histological analysis. In addition, the myocardial area in transition point has three layers in the depth of 1 mm, and the depth-resolved myocardial fiber show different orientation in the different layers. This characteristic was applied for segmentation of the structures of myocardium extending into PV.

  1. [Metabolic support of the ischemic heart during cardiac surgery].

    PubMed

    Luna Ortiz, Pastor; Serrano Valdés, Xenia; Rojas Pérez, Eduardo; de Micheli, Alfredo

    2006-01-01

    We examine [IBM1] the basic principles and clinical results of the metabolic intervention with glucose-insulin-potassium (GIK) solutions in the field of cardiovascular surgery. On the basis of many international publications concerning this subject, and the experience obtained in the operating room of the Instituto Nacional de Cardiologia "Ignacio Chávez", we conclude that the metabolic support wit GIK is a powerful system that provides very useful energy to protect the myocardium during cardiac and non-cardiac surgery. The most recent publications indicate their effects in reducing low output syndromes, due to interventions on the coronary arteries, as well as producing a significant reduction of circulating fatty acids. These effects are produced also in the field of interventional cardiology, where GIK solutions protect the myocardium against damage due to impaired microcirculation. It is evident that these solutions must be utilized in higher concentrations that the initial ones, equal to those employed in laboratory animals. On the other side, it is worthy to remember that it has been always underlined that this treatment represents only a protection for the myocardium. Therefore, its association with other drugs or treatments favoring a good myocardial performance is not contraindicated--on the contrary, it yields better results. The present review presents pharmacological approaches, such as the use of glutamato, aspartate, piruvato, trimetazidina ranolazine and taurine to optimize cardiac energy metabolism, for the management of ischemic heart disease.

  2. Histopathological study on myocardial hypertrophy associated with ischemic heart disease.

    PubMed

    Ishijima, M

    1990-06-01

    The mode and causes of myocardial hypertrophy occurring in association with ischemic heart disease were studied. The investigation involved autopsied hearts (15 cases of subendocardial infarction, 27 of transmural infarction, 20 of non-infarcted three vessel disease and 17 controls) and biopsied materials obtained during coronary-aorta bypass graft surgery (23 patients with angina pectoris and 46 with myocardial infarction). The subendocardial infarction group showed most marked myocardial hypertrophy that reflected extensive infarction and fibrosis, dilatation of the left ventricular cavity and the loss of myocytes. Despite a marked decrease in the number of myocyte layers, the residual myocardium of the left ventricle was uniformly hypertrophic, accompanied by an increase in the heart weight. The larger the area of fibrosis, the more marked was myocardial hypertrophy irrespective of the luminal diameter of the responsible coronary artery. These findings indicate that myocardial hypertrophy associated with ischemic heart disease is enhanced by the compensatory mechanisms for a decrease in the contractile myocardium due to fibrosis.

  3. Canine distemper virus.

    PubMed

    Martella, Vito; Elia, Gabrielle; Buonavoglia, Canio

    2008-07-01

    Vaccine-based prophylaxis has greatly helped to keep distemper disease under control. Notwithstanding, the incidence of canine distemper virus (CDV)-related disease in canine populations throughout the world seems to have increased in the past decades, and several episodes of CDV disease in vaccinated animals have been reported, with nation-wide proportions in some cases. Increasing surveillance should be pivotal to identify new CDV variants and to understand the dynamics of CDV epidemiology. In addition, it is important to evaluate whether the efficacy of the vaccine against these new strains may somehow be affected.

  4. Enhanced preservation of acutely ischemic myocardium with transseptal left ventricular assist.

    PubMed

    Fonger, J D; Zhou, Y; Matsuura, H; Aldea, G S; Shemin, R J

    1994-03-01

    Mechanical support for acute regional ischemia without hemodynamic collapse may be achieved percutaneously with an intraaortic balloon pump (IABP) or with transseptal left ventricular assist (TLVA) while awaiting revascularization. The relative benefits of these two percutaneous transfemoral techniques for the treatment of ischemia were compared in a representative animal model. During 90 minutes of regional coronary occlusion, four groups of 8 pigs were treated with either no support (control), IABP, TLVA, or both IABP and TLVA. Cardioplegic arrest for 30 minutes to simulate coronary grafting was followed by 180 minutes of global reperfusion on bypass. In all groups regional wall motion and interstitial pH in the area at risk were significantly depressed with ischemia, but wall motion fully recovered after reperfusion. However, histochemical staining of the area of necrosis/area at risk was significantly reduced with IABP versus control (20.2% versus 34.1%; p < 0.05) and further significantly reduced with TLVA and IABP + TLVA (10.7% and 6.7% versus IABP alone; p < 0.05). We conclude that in supporting even a modest-sized myocardial region at risk (12% of the left ventricle) the area that went on to infarction was significantly reduced with the use of TLVA over IABP. Regional wall motion and myocardial pH measurements did not reflect this difference in the early reperfusion period. The benefit of TLVA over IABP during more extensive or prolonged ischemia may have real clinical significance.

  5. Temperature measurement within myocardium during in vitro RF catheter ablation.

    PubMed

    Cao, H; Vorperian, V R; Tsai, J Z; Tungjitkusolmun, S; Woo, E J; Webster, J G

    2000-11-01

    While most commercial ablation units and research systems can provide catheter tip temperature during ablation, they do not provide information about the temperature change inside the myocardium, which determines the lesion size. We present the details of a flow simulation and temperature measurement system, which allows the monitoring of the temperature change inside the myocardium during in vitro radio frequency (RF) cardiac catheter ablation at different blood flow rates to which the catheter site may be exposed. We set up a circulation system that simulated different blood flow rates of 0 to 5 L/min at 37 degrees C. We continuously measured the temperature at the catheter tip using the built-in thermistor and inside the myocardium using a three-thermocouple probe. The system provides a means for further study of the temperature inside myocardium during RF catheter ablation under different flow conditions and at different penetration depths.

  6. Cardiac Telocytes in Regeneration of Myocardium After Myocardial Infarction.

    PubMed

    Zhaofu, Liao; Dongqing, Cai

    2016-01-01

    Recent research progress has revealed that a novel type of interstitial cells termed cardiac telocytes (CTs) is found in the interstitium of the heart. We demonstrated that CTs are distributed both longitudinally and within the cross network in the myocardium and that the density of CTs in the atrium-atria and base of the myocardium is higher than that in the middle of the myocardium, while the density of CTs in the epicardium is higher than that in the endocardium. In addition, we documented, for the first time, that the network of CTs in the infarct zone of the myocardium is destroyed during myocardial infarction (MI). This fact shows that, in addition to the death of cardiac myocytes, the previously unrecognized death of CTs is an important mechanism that contributes to the structural damage and poor healing and regeneration observed in the infarcted myocardium. Furthermore, we demonstrated, for the first time, that transplantation of CTs in cases of MI decreases the infarct size and improves myocardial function. The mechanisms behind the beneficial effects of CT transplantation are increased angiogenesis at the infarct site and the border zone, decreased fibrosis in the infarct and non-infarct zones, improved pathological reconstruction of the left ventricle, and increased regeneration of CTs in the infarct zone. Our findings reveal that CTs can be specifically identified by the following characteristics: very small cell bodies, extreme prolongation with some dilation, predisposition to cell death under ischemia, and expression of molecular markers such as c-Kit, CD34, vimentin, and PDGFR-β. CTs act as a structural and functional niche microenvironment in the myocardium and play an essential role in maintaining the integrity of the myocardium and in the regeneration of damaged myocardium.

  7. [Neurogenic stunned myocardium in Pediatrics. A case report].

    PubMed

    Alados Arboledas, F J; Millán-Miralles, L; Millán-Bueno, M P; Expósito-Montes, J F; Santiago-Gutierrez, C; Martínez Padilla, M C

    2015-10-01

    Neurogenic stunned myocardium is an unusual clinical entity. It mimics an acute coronary syndrome with electrocardiographic abnormalities, cardiac dysfunction and elevated cardiac enzymes with absence of obstructive coronary disease. It may occur after a neurosurgical procedure. A case is presented of neurogenic stunned myocardium occurring in a child after removal of a posterior fossa medulloblastoma. The patient developed nodal tachycardia with hemodynamic impairment. The clinical course was satisfactory due to antiarrhythmic therapy, with biochemical, echocardiographic, and clinical improvement within a week.

  8. Lubiprostone induced ischemic colitis.

    PubMed

    Sherid, Muhammed; Sifuentes, Humberto; Samo, Salih; Deepak, Parakkal; Sridhar, Subbaramiah

    2013-01-14

    Ischemic colitis accounts for 6%-18% of the causes of acute lower gastrointestinal bleeding. It is often multifactorial and more commonly encountered in the elderly. Several medications have been implicated in the development of colonic ischemia. We report a case of a 54-year old woman who presented with a two-hour history of nausea, vomiting, abdominal pain, and bloody stool. The patient had recently used lubiprostone with close temporal relationship between the increase in the dose and her symptoms of rectal bleeding. The radiologic, colonoscopic and histopathologic findings were all consistent with ischemic colitis. Her condition improved without any serious complications after the cessation of lubiprostone. This is the first reported case of ischemic colitis with a clear relationship with lubiprostone (Naranjo score of 10). Clinical vigilance for ischemic colitis is recommended for patients receiving lubiprostone who are presenting with abdominal pain and rectal bleeding.

  9. Spiral waves in a model of myocardium

    NASA Astrophysics Data System (ADS)

    Tyson, John J.; Keener, James P.

    1987-11-01

    Myocardial tissue is an excitable medium through which propagate waves of electrical stimulation and muscular contraction. In addition to radially expanding waves of neuromuscular activity characterizing the normal heartbeat, myocardial tissue may also support high frequency, rotating spiral waves of activity which are associated with cardiac pathologies (flutter and fibrillation). Recently Pertsov, Ermakova and Panfilov have presented a numerical study of rotating spiral waves in a two-dimensional excitable medium modeled on the FitzHugh-Nagumo equations, suitably modified to reflect the electrical properties of myocardium. We show that some of their principal numerical results can be reproduced in quantitative detail by a general theory of rotating spiral waves in excitable media. The critical ingredients of our theory are the dispersion of nonlinear plane waves and the effects of curvature on the propagation of wave fronts in two-dimensional media. The close comparison of our analytical results with numerical simulations of the full reaction-diffusion equations lends credence to our theoretical description of spiral waves in excitable media.

  10. Apoptosis in canine distemper.

    PubMed

    Moro, L; de Sousa Martins, A; de Moraes Alves, C; de Araújo Santos, F G; dos Santos Nunes, J E; Carneiro, R A; Carvalho, R; Vasconcelos, A C

    2003-01-01

    Canine distemper is a systemic viral disease characterized by immunosuppression followed by secondary infections. Apoptosis is observed in several immunosuppressive diseases and its occurrence on canine distemper in vivo has not been published. In this study, the occurrence of apoptosis was determined in lymphoid tissues of thirteen naturally infected dogs and nine experimentally inoculated puppies. Healthy dogs were used as negative controls. Samples of lymph nodes, thymus, spleen and brain were collected for histopathological purposes. Sections, 5 microm thick, of retropharingeal lymph nodes were stained by HE, Shorr, Methyl Green-Pyronin and TUNEL reaction. Shorr stained sections were further evaluated by morphometry. Canine distemper virus nucleoprotein was detected by immunohistochemistry. Retropharingeal lymph nodes of naturally and experimentally infected dogs had more apoptotic cells per field than controls. In addition, DNA from thymus of infected dogs were more fragmented than controls. Therefore, apoptosis is increased in lymphoid depletion induced by canine distemper virus and consequently play a role in the immunosuppression seen in this disease.

  11. Clinical canine dental radiography.

    PubMed

    Bannon, Kristin M

    2013-05-01

    The purpose of this article is to provide small animal veterinarians in private practice a guideline for interpretation of the most common findings in canine intraoral radiology. Normal oral and dental anatomy is presented. A brief review of variations of normal, common periodontal and endodontic pathology findings and developmental anomalies is provided.

  12. Vaccines for Canine Leishmaniasis

    PubMed Central

    Palatnik-de-Sousa, Clarisa B.

    2012-01-01

    Leishmaniasis is the third most important vector-borne disease worldwide. Visceral leishmaniasis (VL) is a severe and frequently lethal protozoan disease of increasing incidence and severity due to infected human and dog migration, new geographical distribution of the insect due to global warming, coinfection with immunosuppressive diseases, and poverty. The disease is an anthroponosis in India and Central Africa and a canid zoonosis (ZVL) in the Americas, the Middle East, Central Asia, China, and the Mediterranean. The ZVL epidemic has been controlled by one or more measures including the culling of infected dogs, treatment of human cases, and insecticidal treatment of homes and dogs. However, the use of vaccines is considered the most cost–effective control tool for human and canine disease. Since the severity of the disease is related to the generation of T-cell immunosuppression, effective vaccines should be capable of sustaining or enhancing the T-cell immunity. In this review we summarize the clinical and parasitological characteristics of ZVL with special focus on the cellular and humoral canine immune response and review state-of-the-art vaccine development against human and canine VL. Experimental vaccination against leishmaniasis has evolved from the practice of leishmanization with living parasites to vaccination with crude lysates, native parasite extracts to recombinant and DNA vaccination. Although more than 30 defined vaccines have been studied in laboratory models no human formulation has been licensed so far; however three second-generation canine vaccines have already been registered. As expected for a zoonotic disease, the recent preventive vaccination of dogs in Brazil has led to a reduction in the incidence of canine and human disease. The recent identification of several Leishmania proteins with T-cell epitopes anticipates development of a multiprotein vaccine that will be capable of protecting both humans and dogs against VL. PMID:22566950

  13. Do canine parvoviruses affect canine neurons? An immunohistochemical study.

    PubMed

    Url, A; Schmidt, P

    2005-08-01

    In cats (most of which died from panleukopenia), cerebral neurons have recently been shown to be susceptible to canine parvovirus infection. In addition to positive immunostaining and distinct in situ hybridization signals, signs of neurodegeneration were identified by histopathology, mainly in the diencephalic area. Similar histological lesions of the diencephalic regions in dogs have also attracted attention; therefore, an immunohistochemical study was initiated to determine the possible infection of canine neurons with canine parvoviruses. The study was carried out on formalin-fixed and paraffin-embedded brain tissue, with and without signs of neurodegeneration, from 40 dogs, most of them dying from parvovirus enteritis. Immunohistochemistry, using polyclonal antiserum against canine parvoviruses, was negative in all 40 cases, suggesting that, unlike cats, canine parvoviruses do not seem capable of infecting canine neurons.

  14. Evidence of canine distemper and suggestion of preceding parvovirus-myocarditis in a Eurasian badger (Meles meles).

    PubMed

    Burtscher, Hugo; Url, Angelika

    2007-03-01

    An approximately 1.5-yr-old free-ranging male Eurasian badger (Meles meles) from the eastern part of Austria had macroscopic and microscopic lesions consistent with canine distemper virus infection, including nonsuppurative meningoencephalitis, interstitial pneumonia with accumulation of macrophages in alveoli that contained intranuclear inclusion bodies, vesicular exanthema of the ventral abdomen, and atrophy of lymphoid tissues. Canine distemper virus-antigen was demonstrable in a variety of organs by using immunohistology. In addition, there were widespread areas of fibrosis in the myocardium that were rich in collagen and paucicellular. Because such changes are comparable with sequelae of the acute cardiac form of canine parvovirus (CPV) infection in dogs, it was speculated that this badger may have experienced CPV myocarditis as a cub but that the corresponding antigen or DNA was not detectable due to resolution of the disease.

  15. Diffusion of water in cat ventricular myocardium

    PubMed Central

    1978-01-01

    The rates of diffusion of tritiated water (THO) and [14C]sucrose across cat right ventricular myocardium were studied at 23 degrees C in an Ussing-type diffusion cell, recording the time-course of increase in concentration of tracer in one chamber over 4--6 h after adding tracers to the other. Sucrose data were fitted with a model for a homogeneous sheet of uneven thickness in which the tissue is considered to be an array of parallel independent pathways (parallel pathway model) of varying length. The volume of the sucrose diffusion space, presumably a wholly extracellular pathway, was 23% of the tissue or 27.4 +/-1.7% (mean +/- SEM; n=11) of the tissue water. The effective intramyocardial sucrose diffusion coefficient, D8, was 1.51 +/- 0.19 X 10(-6)cm2.s-1 (n=11). Combining these data with earlier data, D8 was 22.6 +/- 1.1% (n=95) of the free diffusion coefficient in aqueous solution D degrees 8. The parallel pathway model and a dead-end pore model, which might have accounted for intracellular sequestration of water, gave estimates of DW/D degrees W (observed/free) of 15%. Because hindrance to water diffusion must be less than for sucrose (where D8/D degrees 8=22.6%), this showed the inadequacy of these models to account simultaneously for the diffusional resistance and the tissue water content. The third or cell-matrix model, a heterogeneous system of permeable cells arrayed in the extracellular matrix, allowed logical and geometrically reasonable interpretations of the steady-state data and implied estimates of DW in the cellular and extracellular fluid of approximately 25% of the aqueous diffusion coefficient. PMID:722277

  16. Bioengineering Human Myocardium on Native Extracellular Matrix

    PubMed Central

    Guyette, Jacques P.; Charest, Jonathan M; Mills, Robert W; Jank, Bernhard J.; Moser, Philipp T.; Gilpin, Sarah E.; Gershlak, Joshua R.; Okamoto, Tatsuya; Gonzalez, Gabriel; Milan, David J.; Gaudette, Glenn R.; Ott, Harald C.

    2015-01-01

    Rationale More than 25 million individuals suffer from heart failure worldwide, with nearly 4,000 patients currently awaiting heart transplantation in the United States. Donor organ shortage and allograft rejection remain major limitations with only about 2,500 hearts transplanted each year. As a theoretical alternative to allotransplantation, patient-derived bioartificial myocardium could provide functional support and ultimately impact the treatment of heart failure. Objective The objective of this study is to translate previous work to human scale and clinically relevant cells, for the bioengineering of functional myocardial tissue based on the combination of human cardiac matrix and human iPS-derived cardiac myocytes. Methods and Results To provide a clinically relevant tissue scaffold, we translated perfusion-decellularization to human scale and obtained biocompatible human acellular cardiac scaffolds with preserved extracellular matrix composition, architecture, and perfusable coronary vasculature. We then repopulated this native human cardiac matrix with cardiac myocytes derived from non-transgenic human induced pluripotent stem cells (iPSCs) and generated tissues of increasing three-dimensional complexity. We maintained such cardiac tissue constructs in culture for 120 days to demonstrate definitive sarcomeric structure, cell and matrix deformation, contractile force, and electrical conduction. To show that functional myocardial tissue of human scale can be built on this platform, we then partially recellularized human whole heart scaffolds with human iPSC-derived cardiac myocytes. Under biomimetic culture, the seeded constructs developed force-generating human myocardial tissue, showed electrical conductivity, left ventricular pressure development, and metabolic function. Conclusions Native cardiac extracellular matrix scaffolds maintain matrix components and structure to support the seeding and engraftment of human iPS-derived cardiac myocytes, and enable

  17. Hibernating myocardium results in partial sympathetic denervation and nerve sprouting

    PubMed Central

    Fernandez, Stanley F.; Ovchinnikov, Vladislav; Canty, John M.

    2013-01-01

    Hibernating myocardium due to chronic repetitive ischemia is associated with regional sympathetic nerve dysfunction and spontaneous arrhythmic death in the absence of infarction. Although inhomogeneity in regional sympathetic innervation is an acknowledged substrate for sudden death, the mechanism(s) responsible for these abnormalities in viable, dysfunctional myocardium (i.e., neural stunning vs. sympathetic denervation) and their association with nerve sprouting are unknown. Accordingly, markers of sympathetic nerve function and nerve sprouting were assessed in subendocardial tissue collected from chronically instrumented pigs with hibernating myocardium (n = 18) as well as sham-instrumented controls (n = 7). Hibernating myocardium exhibited evidence of partial sympathetic denervation compared with the normally perfused region and sham controls, with corresponding regional reductions in tyrosine hydroxylase protein (−32%, P < 0.001), norepinephrine uptake transport protein (−25%, P = 0.01), and tissue norepinephrine content (−45%, P < 0.001). Partial denervation induced nerve sprouting with regional increases in nerve growth factor precursor protein (31%, P = 0.01) and growth associated protein-43 (38%, P < 0.05). All of the changes in sympathetic nerve markers were similar in animals that developed sudden death (n = 9) compared with electively terminated pigs with hibernating myocardium (n = 9). In conclusion, sympathetic nerve dysfunction in hibernating myocardium is most consistent with partial sympathetic denervation and is associated with regional nerve sprouting. The extent of sympathetic remodeling is similar in animals that develop sudden death compared with survivors; this suggests that sympathetic remodeling in hibernating myocardium is not an independent trigger for sudden death. Nevertheless, sympathetic remodeling likely contributes to electrical instability in combination with other factors. PMID:23125211

  18. Remote Limb Ischemic Postconditioning Protects Against Neonatal Hypoxic–Ischemic Brain Injury in Rat Pups by the Opioid Receptor/Akt Pathway

    PubMed Central

    Zhou, Yilin; Fathali, Nancy; Lekic, Tim; Ostrowski, Robert P.; Chen, Chunhua; Martin, Robert D.; Tang, Jiping; Zhang, John H.

    2013-01-01

    Background and Purpose Remote ischemic postconditoning, a phenomenon in which brief ischemic stimuli of 1 organ protect another organ against an ischemic insult, has been demonstrated to protect the myocardium and adult brain in animal models. However, mediators of the protection and underlying mechanisms remain to be elucidated. In the present study, we tested the hypothesis that remote limb ischemic postconditioning applied immediately after hypoxia provides neuroprotection in a rat model of neonatal hypoxia–ischemia (HI) by mechanisms involving activation of the opioid receptor/phosphatidylinositol-3-kinase/Akt signaling pathway. Methods HI was induced in postnatal Day 10 rat pups by unilateral carotid ligation and 2 hours of hypoxia. Limb ischemic postconditioning was induced by 4 conditioning cycles of 10 minutes of ischemia and reperfusion on both hind limbs immediately after HI. The opioid antagonist naloxone, phosphatidylinositol-3-kinase inhibitor wortmannin, or opioid agonist morphine was administered to determine underlying mechanisms. Infarct volume, brain atrophy, and neurological outcomes after HI were evaluated. Expression of phosphorylated Akt, Bax, and phosphorylated ERK1/2 was determined by Western blotting. Results Limb ischemic postconditioning significantly reduced infarct volume at 48 hours and improved functional outcomes at 4 weeks after HI. Naloxone and wortmannin abrogated the postconditioning-mediated infarct-limiting effect. Morphine given immediately after hypoxia also decreased infarct volume. Furthermore, limb ischemic postconditioning recovered Akt activity and decreased Bax expression, whereas no differences in phosphorylated ERK1/2expression were observed. Conclusions Limb ischemic postconditioning protects against neonatal HI brain injury in rats by activating the opioid receptor/phosphatidylinositol-3-kinase/Akt signaling pathway. PMID:21183744

  19. Canine parvovirus: current perspective.

    PubMed

    Nandi, S; Kumar, Manoj

    2010-06-01

    Canine parvovirus 2 (CPV-2) has been considered to be an important pathogen of domestic and wild canids and has spread worldwide since its emergence in 1978. It has been reported from Asia, Australia, New Zealand, the Americas and Europe. Two distinct parvoviruses are now known to infect dogs-the pathogenic CPV-2 and CPV-1 or the minute virus of canine (MVC). CPV-2, the causative agent of acute hemorrhagic enteritis and myocarditis in dogs, is one of the most important pathogenic viruses with high morbidity (100%) and frequent mortality up to 10% in adult dogs and 91% in pups. The disease condition has been complicated further due to emergence of a number of variants namely CPV-2a, CPV-2b and CPV-2c over the years and involvement of domestic and wild canines. There are a number of different serological and molecular tests available for prompt, specific and accurate diagnosis of the disease. Further, both live attenuated and inactivated vaccines are available to control the disease in animals. Besides, new generation vaccines namely recombinant vaccine, peptide vaccine and DNA vaccine are in different stages of development and offer hope for better management of the disease in canines. However, new generation vaccines have not been issued license to be used in the field condition. Again, the presence of maternal antibodies often interferes with the active immunization with live attenuated vaccine and there always exists a window of susceptibility in spite of following proper immunization regimen. Lastly, judicious use of the vaccines in pet dogs, stray dogs and wild canids keeping in mind the new variants of the CPV-2 along with the proper sanitation and disinfection practices must be implemented for the successful control the disease.

  20. [Canine histoplasmosis in Japan].

    PubMed

    Sano, Ayako; Miyaji, Makoto

    2003-01-01

    Histoplasmosis is a fungal infection caused by Histoplasma capsulatum and is distributed a worldwide. Although the disease has been treated as an imported mycosis, some autochthonous human, 1 equine and 4 canine cases suggested that the disease is endemic. Histoplasmosis is classified depending on the variety of causative agent. Histoplasmosis farciminosi known as pseudofarcy, is manifested only in Perissodactyla where it invades lymph nodes and lymph ducts, and is recognized by isolation from horses. Historically, Japan was one of the endemic areas of pseudofarcy before World War II, and more than 20,000 cases were recorded in horses used by the military. Interestingly, Japanese canine histoplasmosis uniformly showed skin ulcers and granulomatous lesions on the skin without pulmonary or gastrointestinal involvement, both of which were very similar to pseudofarcy. It was diagnosed as histoplasmosis by the detection of internal transcribed spacer legions of rRNA gene of H. capsulatum from paraffin embedded tissue samples. Furthermore, the fungal isolate from the human case with no history of going abroad or immigrating was identified as H. capsulatum var. farciminosum by a gene sequence. These facts indicated that pseudofarcy is not only an infectious disease in horses, but also a zoonotic fungal infection. Japanese autochthonous canine histoplasmosis might be a heteroecism of pseudofarcy because of its likeness to the human case, the similarity of clinical manifestations and the historical background at this stage.

  1. Ischemic Colitis Revealing Polyarteritis Nodosa

    PubMed Central

    Hamzaoui, Amira; Litaiem, Noureddine; Smiti Khanfir, M.; Ayadi, Sofiene; Nfoussi, Haifa; Houman, M. H.

    2013-01-01

    Ischemic colitis is one of the most common intestinal ischemic injuries. It results from impaired perfusion of blood to the bowel and is rarely caused by vasculitis. We report a case of ischemic colitis revealing polyarteritis nodosa (PAN) in a 55-year-old man. Histological examination of the resected colon led to the diagnosis of PAN. PMID:24382967

  2. Noncompaction myocardium in association with type Ib glycogen storage disease.

    PubMed

    Goeppert, Benjamin; Lindner, Martin; Vogel, Monika Nadja; Warth, Arne; Stenzinger, Albrecht; Renner, Marcus; Schnabel, Philipp; Schirmacher, Peter; Autschbach, Frank; Weichert, Wilko

    2012-10-15

    Noncompaction myocardium is a rare disorder assumed to occur as an arrest of the compaction process during the normal development of the heart. Left ventricular noncompaction has been reported to be associated with a variety of cardiac and extracardiac, especially neuromuscular abnormalities. Moreover, it has been suggested that metabolic alterations could be responsible for the noncompaction. However, no association of noncompaction myocardium with type Ib glycogen storage disease (GSD) has been reported so far. Type Ib GSD is due to a defect of a transmembrane protein which results, similar to type Ia GSD, in hypoglycemia, a markedly enlarged liver and, additionally, in neutropenia, recurrent infections, and inflammatory bowel disease. Until now, no muscular or cardiac involvement has been described in type Ib GSD patients. The present case represents the first report of a noncompaction myocardium in a child with type Ib GSD who died of sudden clinical deterioration at the age of four.

  3. Maternal obesity induces fibrosis in fetal myocardium of sheep

    PubMed Central

    Huang, Yan; Yan, Xu; Zhao, Jun X.; Zhu, Mei J.; McCormick, Richard J.; Ford, Stephen P.; Nathanielsz, Peter W.; Ren, Jun

    2010-01-01

    Maternal obesity (MO) has harmful effects on both fetal development and subsequent offspring health. The impact of MO on fetal myocardium development has received little attention. Fibrogenesis is regulated by the transforming growth factor-β (TGF-β)/p38 signaling pathway. Using the well-established model of MO in pregnant sheep, we evaluated the effect of MO on TGF-β/p38 and collagen accumulation in fetal myocardium. Nonpregnant ewes were assigned to a control diet [Con, fed 100% of National Research Council (NRC) nutrient recommendations] or obesogenic diet (OB, fed 150% of NRC recommendations) from 60 days before conception. Fetal ventricular muscle was sampled at 75 and 135 days of gestation (dG). At 75 dG, the expression of precursor TGF-β was 39.9 ± 9.9% higher (P < 0.05) in OB than Con fetal myocardium, consistent with the higher content of phosphorylated Smad3 in OB myocardium. The phosphorylation of p38 tended to be higher in OB myocardium (P = 0.08). In addition, enhanced Smad complexes were bound to Smad-binding elements in 75 dG OB fetal myocardium measured by DNA mobility shift assay (130.2 ± 26.0% higher, P < 0.05). Similar elevation of TGF-β signaling was observed in OB fetal myocardium at 135 dG. Total collagen concentration in OB was greater than Con fetal myocardium (2.42 ± 0.16 vs. 1.87 ± 0.04%, P < 0.05). Matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-3 were higher in the Con group compared with OB sheep (43.86 ± 16.01 and 37.23 ± 7.97% respectively, P < 0.05). In summary, MO results in greater fetal heart connective tissue accumulation associated with an upregulated TGF-β/p38 signaling pathway at late gestation; such changes would be expected to negatively impact offspring heart function. PMID:20876759

  4. System of scale-selective tomography of myocardium birefringence

    NASA Astrophysics Data System (ADS)

    Ushenko, O. G.; Boichuk, T. M.; Bachinskiy, V. T.; Vanchuliak, O. Ya.; Minzer, O. P.; Ushenko, Yu. O.; Dubolazov, O. V.; Savich, V. O.

    2015-09-01

    This research presents the results of investigation of laser polarization fluorescence of biological layers (histological sections of the myocardium). The polarized structure of autofluorescence imaging layers of biological tissues was detected and investigated. Proposed the model of describing the formation of polarization inhomogeneous of autofluorescence imaging biological optically anisotropic layers. On this basis, analytically and experimentally tested to justify the method of laser polarimetry autofluorescent. Analyzed the effectiveness of this method in the postmortem diagnosis of infarction. The objective criteria (statistical moments) of differentiation of autofluorescent images of histological sections myocardium were defined. The operational characteristics (sensitivity, specificity, accuracy) of these technique were determined.

  5. Hypokinesia of myocardium of perfused rat heart at different oxygenation of myoglobin and redox state of cytochrome

    NASA Astrophysics Data System (ADS)

    Frank, Klaus H.; Zuendorf, J.; Tauschek, D.; Kessler, Manfred D.

    2002-06-01

    Questions about development of hypo-kinetic zones in myocardium of patients suffering from severe coronary heart disease are discussed controversially among heart surgeons. We established a model for isolated and hemoglobin free perfusion of rat heart in which sufficient flow was established within all capillaries and thus existence of ischemic capillaries could be excluded. A definite diagnosis of tissue anoxia is only possible by optical measurements of the oxidation and the reduction (redox state) of the cytochrome oxidase of intact myocytes. Therefore, we used an EMPHO for this kind of measurements. Intracellular oxygenation of myoglobin oxygenation (MbO2) and redox state of cytochrome aa3, b and c were recorded in the outer wall of working, hypo-kinetic and a-kinetic myocardium. As a result of our investigations we were able to prove that by lowering at the venous end of capillaries tissue pO2 and myoglobin oxygenation stepwise below 5 mmHg and 50% of saturation respectively, a continuous decrease of myocardial contractility could be achieved.

  6. Nanovector-based prolyl hydroxylase domain 2 silencing system enhances the efficiency of stem cell transplantation for infarcted myocardium repair

    PubMed Central

    Zhu, Kai; Lai, Hao; Guo, Changfa; Li, Jun; Wang, Yulin; Wang, Lingyan; Wang, Chunsheng

    2014-01-01

    Mesenchymal stem cell (MSC) transplantation has attracted much attention in myocardial infarction therapy. One of the limitations is the poor survival of grafted cells in the ischemic microenvironment. Small interfering RNA-mediated prolyl hydroxylase domain protein 2 (PHD2) silencing in MSCs holds tremendous potential to enhance their survival and paracrine effect after transplantation. However, an efficient and biocompatible PHD2 silencing system for clinical application is lacking. Herein, we developed a novel PHD2 silencing system based on arginine-terminated generation 4 poly(amidoamine) (Arg-G4) nanoparticles. The system exhibited effective and biocompatible small interfering RNA delivery and PHD2 silencing in MSCs in vitro. After genetically modified MSC transplantation in myocardial infarction models, MSC survival and paracrine function of IGF-1 were enhanced significantly in vivo. As a result, we observed decreased cardiomyocyte apoptosis, scar size, and interstitial fibrosis, and increased angiogenesis in the diseased myocardium, which ultimately attenuated ventricular remodeling and improved heart function. This work demonstrated that an Arg-G4 nanovector-based PHD2 silencing system could enhance the efficiency of MSC transplantation for infarcted myocardium repair. PMID:25429216

  7. Ischemic Nerve Block.

    ERIC Educational Resources Information Center

    Williams, Ian D.

    This experiment investigated the capability for movement and muscle spindle function at successive stages during the development of ischemic nerve block (INB) by pressure cuff. Two male subjects were observed under six randomly ordered conditions. The duration of index finger oscillation to exhaustion, paced at 1.2Hz., was observed on separate…

  8. Restoration of missing or misplaced canines.

    PubMed

    Bower, C F; Reinhardt, R A

    1985-06-01

    Restorative treatments for canines were discussed to correct three clinical abnormalities: (1) fully erupted permanent canine in the lateral incisor position, (2) missing permanent canines, and (3) partially exposed canines in normal arch position. The primary concerns are the development of esthetics, anterior guidance, and adequate support for fixed restorations.

  9. Ischemic optic neuropathy.

    PubMed

    Hayreh, Sohan Singh

    2009-01-01

    Ischemic optic neuropathy is one of the major causes of blindness or seriously impaired vision, yet there is disagreement as to its pathogenesis, clinical features and especially its management. This is because ischemic optic neuropathy is not one disease but a spectrum of several different types, each with its own etiology, pathogenesis, clinical features and management. They cannot be lumped together. Ischemic optic neuropathy is primarily of two types: anterior (AION) and posterior (PION), involving the optic nerve head (ONH) and the rest of the optic nerve respectively. Furthermore, both AION and PION have different subtypes. AION comprises arteritic (A-AION - due to giant cell arteritis) and, non-arteritic (NA-AION - due to causes other than giant cell arteritis); NA-AION can be further classified into classical NA-AION and incipient NA-AION. PION consists of arteritic (A-PION - due to giant cell arteritis), non-arteritic (NA-PION - due to causes other than giant cell arteritis), and surgical (a complication of several systemic surgical procedures). Thus, ischemic optic neuropathy consists of six distinct types of clinical entities. NA-AION is by far the most common type and one of the most prevalent and visually crippling diseases in the middle-aged and elderly. A-AION, though less common, is an ocular emergency and requires early diagnosis and immediate treatment with systemic high dose corticosteroids to prevent further visual loss, which is entirely preventable. Controversy exists regarding the pathogenesis, clinical features and especially management of the various types of ischemic optic neuropathy because there are multiple misconceptions about its many fundamental aspects. Recently emerging information on the various factors that influence the optic nerve circulation, and also the various systemic and local risk factors which play important roles in the development of various types of ischemic optic neuropathy have given us a better understanding of

  10. Lidocaine Enhances Contractile Function of Ischemic Myocardial Regions in Mouse Model of Sustained Myocardial Ischemia

    PubMed Central

    Kania, Gabriela; Osto, Elena; Jakob, Philipp; Krasniqi, Nazmi; Beck-Schimmer, Beatrice; Blyszczuk, Przemyslaw; Eriksson, Urs

    2016-01-01

    Rationale Perioperative myocardial ischemia is common in high-risk patients. The use of interventional revascularisation or even thrombolysis is limited in this patient subset due to exceedingly high bleeding risks. Blockade of voltage-gated sodium channels (VGSC) with lidocaine had been suggested to reduce infarct size and cardiomyocyte cell death in ischemia/reperfusion models. However, the impact of lidocaine on cardiac function during sustained ischemia still remains unclear. Methods Sustained myocardial ischemia was induced by ligation of the left anterior descending artery in 12–16 weeks old male BALB/c mice. Subcutaneous lidocaine (30 mg/kg) was used to block VGSC. Cardiac function was quantified at baseline and at 72h by conventional and speckle-tracking based echocardiography to allow high-sensitivity in vivo phenotyping. Infarct size and cardiomyocyte cell death were assessed post mortem histologically and indirectly using troponin measurements. Results Ischemia strongly impaired both, global systolic and diastolic function, which were partially rescued in lidocaine treated in mice. No differences regarding infarct size and cardiomyocyte cell death were observed. Mechanistically, and as shown with speckle-tracking analysis, lidocaine specifically improves residual contractility in the ischemic but not in the remote, non-ischemic myocardium. Conclusion VGSC blockade with lidocaine rescues function of ischemic myocardium as a potential bridging to revascularisation in the setting of perioperative myocardial ischemia. PMID:27140425

  11. Engineering and Visualization of Bacteria for Targeting Infarcted Myocardium

    PubMed Central

    Le, Uyenchi N; Kim, Hyung-Seok; Kwon, Jin-Sook; Kim, Mi Yeon; Nguyen, Vu H; Jiang, Sheng Nan; Lee, Byeong-Il; Hong, Yeongjin; Shin, Myung Geun; Rhee, Joon Haeng; Bom, Hee-Seung; Ahn, Youngkeun; Gambhir, Sanjiv S; Choy, Hyon E; Min, Jung-Joon

    2011-01-01

    Optimization of the specific affinity of cardiac delivery vector could significantly improve the efficiency of gene/protein delivery, yet no cardiac vectors to date have sufficient target specificity for myocardial infarction (MI). In this study, we explored bacterial tropism for infarcted myocardium based on our previous observations that certain bacteria are capable of targeting the hypoxic regions in solid tumors. Out of several Escherichia coli or Salmonella typhimurium strains, the S. typhimurium defective in the synthesis of ppGpp (ΔppGpp S. typhimurium) revealed accumulation and selective proliferation in the infarcted myocardium without spillover to noncardiac tissue. The Salmonellae that were engineered to express a variant of Renilla luciferase gene (RLuc8), under the control of the E. coli arabinose operon promoter (PBAD), selectively targeted and delivered RLuc8 in the infarcted myocardium only upon injection of -arabinose. An examination of the infarct size before and after infection, and estimations of C-reactive protein (CRP) and procalcitonin indicated that intravenous injection of ΔppGpp S. typhimurium did not induce serious local or systemic immune reactions. This current proof-of-principle study demonstrates for the first time the capacity of Salmonellae to target infarcted myocardium and to serve as a vehicle for the selective delivery of therapeutic agents in MI. PMID:21364539

  12. Three-dimensional imaging of the myocardium with isotopes

    NASA Technical Reports Server (NTRS)

    Budinger, T. F.

    1975-01-01

    Three methods of imaging the three-dimensional distribution of isotopes in the myocardium are discussed. Three-dimensional imaging was examined using multiple Anger-camera views. Longitudinal tomographic images with compensation for blurring were studied. Transverse-section reconstruction using coincidence detection of annihilation gammas from positron emitting isotopes was investigated.

  13. Engineering and visualization of bacteria for targeting infarcted myocardium.

    PubMed

    Le, Uyenchi N; Kim, Hyung-Seok; Kwon, Jin-Sook; Kim, Mi Yeon; Nguyen, Vu H; Jiang, Sheng Nan; Lee, Byeong-Il; Hong, Yeongjin; Shin, Myung Geun; Rhee, Joon Haeng; Bom, Hee-Seung; Ahn, Youngkeun; Gambhir, Sanjiv S; Choy, Hyon E; Min, Jung-Joon

    2011-05-01

    Optimization of the specific affinity of cardiac delivery vector could significantly improve the efficiency of gene/protein delivery, yet no cardiac vectors to date have sufficient target specificity for myocardial infarction (MI). In this study, we explored bacterial tropism for infarcted myocardium based on our previous observations that certain bacteria are capable of targeting the hypoxic regions in solid tumors. Out of several Escherichia coli or Salmonella typhimurium strains, the S. typhimurium defective in the synthesis of ppGpp (ΔppGpp S. typhimurium) revealed accumulation and selective proliferation in the infarcted myocardium without spillover to noncardiac tissue. The Salmonellae that were engineered to express a variant of Renilla luciferase gene (RLuc8), under the control of the E. coli arabinose operon promoter (P(BAD)), selectively targeted and delivered RLuc8 in the infarcted myocardium only upon injection of L-arabinose. An examination of the infarct size before and after infection, and estimations of C-reactive protein (CRP) and procalcitonin indicated that intravenous injection of ΔppGpp S. typhimurium did not induce serious local or systemic immune reactions. This current proof-of-principle study demonstrates for the first time the capacity of Salmonellae to target infarcted myocardium and to serve as a vehicle for the selective delivery of therapeutic agents in MI.

  14. [Morphological signs of impaired excitation conduction in the myocardium].

    PubMed

    Kapustin, A V

    2005-01-01

    The article describes morphological changes in cardiac muscular fibers and cardiomyocytes secondary to disorders in conduction of excitation in the myocardium. These changes may indicate cardiac arrest as a result of reflex impacts including cases of damage which is not lethal.

  15. Melatonin-induced glycosaminoglycans augmentation in myocardium remote to infarction.

    PubMed

    Drobnik, J; Tosik, D; Piera, L; Szczepanowska, A; Olczak, S; Zielinska, A; Liberski, P P; Ciosek, J

    2013-12-01

    Elevated levels of collagen as well as transient increases of glycosaminoglycans (GAG) have been shown in the myocardium remote to the infarction. The aim of the study is to observe the effect of melatonin on the accumulation of collagen and GAG in the left ventricle wall, remote to the infarction. A second aim is to determine whether the effect of the pineal indole is mediated by the membrane melatonin receptors of heart fibroblasts. Rats with myocardial infarction induced by ligation of the left coronary artery were treated with melatonin at a dose of 60 μg/100 g b.w. or vehicle (2% ethanol in 0.9% NaCl). The results were compared with an untreated control. In the second part of the study, the fibroblasts from the non-infarcted part of myocardium were isolated and cultured. Melatonin at a range of concentrations from 10(-8) M to 10(-6) M was applied to the fibroblast cultures. In the final part of the study, the influence of luzindole (10(-6) M), the melatonin membrane receptor inhibitor, on melatonin-induced GAG augmentation was investigated. Both collagen and GAG content were measured in the experiment. Melatonin elevated GAG content in the myocardium remote to the infarcted heart. Collagen level was not changed by pineal indoleamine. Fibroblasts isolated from the myocardium varied in shape from fusiform to spindle-shaped. Moreover, the pineal hormone (10(-7)M and 10(-6)M) increased GAG accumulation in the fibroblast culture. Luzindole inhibited melatonin-induced elevation of GAG content at 10(-6)M. Melatonin increased GAG content in the myocardium remote to infarction. This effect was dependent on the direct influence of the pineal indole on the heart fibroblasts. The melatonin-induced GAG elevation is blocked by luzindole, the melatonin membrane receptors inhibitor, indicating a direct effect of this indole.

  16. Canine mammary gland tumors.

    PubMed

    Sorenmo, Karin

    2003-05-01

    The National Consensus Group recommends that all women with tumors larger than 1 cm be offered chemotherapy regardless of tumor histology of lymph node status. This recommendation is to ensure that everyone at risk for failing, even though the risk may be low in women with relatively small tumors and favorable histology, has a choice and receives the benefit of adjuvant chemotherapy. This type of treatment recommendation may also be made in dogs based on recognized, well-accepted prognostic factors such as tumor size, stage, type, and histologic differentiation. Based on the limited clinical information available in veterinary medicine, the drugs that are effective in human breast cancer, such as cyclophosphamide, 5-fluorouracil, and doxorubicin, may also have a role in the treatment of malignant mammary gland tumors in dogs. Randomized prospective studies are needed, however, to evaluate the efficacy of chemotherapy in dogs with high-risk mammary gland tumors and to determine which drugs and protocols are the most efficacious. Until such studies are performed, the treatment of canine mammary gland tumors will be based on the individual oncologist's understanding of tumor biology, experience, interpretation of the available studies, and a little bit of gut-feeling. Table 2 is a proposal for treatment guidelines for malignant canine mammary gland tumors according to established prognostic factors, results from published veterinary studies, and current recommendations for breast cancer treatment in women.

  17. Canine spinal cord glioma.

    PubMed

    Rissi, Daniel R; Barber, Renee; Burnum, Annabelle; Miller, Andrew D

    2017-01-01

    Spinal cord glioma is uncommonly reported in dogs. We describe the clinicopathologic and diagnostic features of 7 cases of canine spinal cord glioma and briefly review the veterinary literature on this topic. The median age at presentation was 7.2 y. Six females and 1 male were affected and 4 dogs were brachycephalic. The clinical course lasted from 3 d to 12 wk, and clinical signs were progressive and associated with multiple suspected neuroanatomic locations in the spinal cord. Magnetic resonance imaging of 6 cases revealed T2-weighted hyperintense lesions with variable contrast enhancement in the spinal cord. All dogs had a presumptive clinical diagnosis of intraparenchymal neoplasia or myelitis based on history, advanced imaging, and cerebrospinal fluid analysis. Euthanasia was elected in all cases because of poor outcome despite anti-inflammatory or immunosuppressive treatment or because of poor prognosis at the time of diagnosis. Tumor location during autopsy ranged from C1 to L6, with no clear predilection for a specific spinal cord segment. The diagnosis was based on histopathology and the immunohistochemistry expression of glial fibrillary acidic protein, oligodendrocyte lineage transcription factor 2, 2',3'-cyclic-nucleotide 3'-phosphodiesterase, neuron-specific enolase, synaptophysin, and Ki-67. Diagnoses consisted of 4 cases of oligodendroglioma, 2 cases of gliomatosis cerebri, and 1 astrocytoma. This case series further defines the clinicopathologic features of canine spinal glioma and highlights the need for comprehensive immunohistochemistry in addition to routine histopathology to confirm the diagnosis of these tumors.

  18. DRESS and Ischemic Stroke.

    PubMed

    Cahyanur, Rahmat; Oktavia, Dina; Koesno, Sukamto

    2012-07-01

    DRESS (drug rash eosinophilia and systemic symptoms) is a life threatening condition characterized by skin rash, fever, leucocytosis with eosinophilia or atypical lymphocytosis, lymphadenopathy, and internal organ involvement. This case report would like to describe an interesting case of DRESS coincidence with ischemic stroke. A 38 year old woman had been admitted with skin rash and fever since four days before. Four weeks before admission she received antibiotic and multivitamin for one week. The patient looked ill, with body temperature 38.0°C. Marked physical findings were cervical lymphadenopathy and hepatomegaly. Dermatological examination finding was generalized exanthema. Laboratory evaluation showed leucocytosis, eosinophilia, and increased level of ALT and AST. During hospitalization the patient also suffered from ischemic stroke. Treatments administered in this patient were oxygen, adequate intravenous fluid, parenteral nutrition, methyl prednisolone, cethirizin bid, ranitidin bid, and antibiotic. The antibiotic treatment in this case was performed with graded challenge or test dosing.

  19. Acute ischemic stroke update.

    PubMed

    Baldwin, Kathleen; Orr, Sean; Briand, Mary; Piazza, Carolyn; Veydt, Annita; McCoy, Stacey

    2010-05-01

    Stroke is the third most common cause of death in the United States and is the number one cause of long-term disability. Legislative mandates, largely the result of the American Heart Association, American Stroke Association, and Brain Attack Coalition working cooperatively, have resulted in nationwide standardization of care for patients who experience a stroke. Transport to a skilled facility that can provide optimal care, including immediate treatment to halt or reverse the damage caused by stroke, must occur swiftly. Admission to a certified stroke center is recommended for improving outcomes. Most strokes are ischemic in nature. Acute ischemic stroke is a heterogeneous group of vascular diseases, which makes targeted treatment challenging. To provide a thorough review of the literature since the 2007 acute ischemic stroke guidelines were developed, we performed a search of the MEDLINE database (January 1, 2004-July 1, 2009) for relevant English-language studies. Results (through July 1, 2009) from clinical trials included in the Internet Stroke Center registry were also accessed. Results from several pivotal studies have contributed to our knowledge of stroke. Additional data support the efficacy and safety of intravenous alteplase, the standard of care for acute ischemic stroke since 1995. Due to these study results, the American Stroke Association changed its recommendation to extend the time window for administration of intravenous alteplase from within 3 hours to 4.5 hours of symptom onset; this recommendation enables many more patients to receive the drug. Other findings included clinically useful biomarkers, the role of inflammation and infection, an expanded role for placement of intracranial stents, a reduced role for urgent carotid endarterectomy, alternative treatments for large-vessel disease, identification of nontraditional risk factors, including risk factors for women, and newly published pediatric stroke guidelines. In addition, new devices for

  20. Coregistration of magnetic resonance and single photon emission computed tomography images for noninvasive localization of stem cells grafted in the infarcted rat myocardium.

    PubMed

    Shen, Dinggang; Liu, Dengfeng; Cao, Zixiong; Acton, Paul D; Zhou, Rong

    2007-01-01

    This paper demonstrates the application of mutual information based coregistration of radionuclide and magnetic resonance imaging (MRI) in an effort to use multimodality imaging for noninvasive localization of stem cells grafted in the infarcted myocardium in rats. Radionuclide imaging such as single photon emission computed tomography (SPECT) or positron emission tomography (PET) inherently has high sensitivity and is suitable for tracking of labeled stem cells, while high-resolution MRI is able to provide detailed anatomical and functional information of myocardium. Thus, coregistration of PET or SPECT images with MRI will map the location and distribution of stem cells on detailed myocardium structures. To validate this coregistration method, SPECT data were simulated by using a Monte Carlo-based projector that modeled the pinhole-imaging physics assuming nonzero diameter and photon penetration at the edge. Translational and rotational errors of the coregistration were examined with respect to various SPECT activities, and they are on average about 0.50 mm and 0.82 degrees , respectively. Only the rotational error is dependent on activity of SPECT data. Stem cells were labeled with (111)Indium oxyquinoline and grafted in the ischemic myocardium of a rat model. Dual-tracer small-animal SPECT images were acquired, which allowed simultaneous detection of (111)In-labeled stem cells and of [(99m)Tc]sestamibi to assess myocardial perfusion deficit. The same animals were subjected to cardiac MRI. A mutual-information-based coregistration method was then applied to the SPECT and MRIs. By coregistration, the (111)In signal from labeled cells was mapped into the akinetic region identified on cine MRIs; the regional perfusion deficit on the SPECT images also coincided with the akinetic region on the MR image.

  1. Burn-induced subepicardial injury in frog heart: a simple model mimicking ST segment changes in ischemic heart disease.

    PubMed

    Kazama, Itsuro

    2016-02-01

    To mimic ischemic heart disease in humans, several animal models have been created, mainly in rodents by surgically ligating their coronary arteries. In the present study, by simply inducing burn injuries on the bullfrog heart, we reproduced abnormal ST segment changes in the electrocardiogram (ECG), mimicking those observed in ischemic heart disease, such as acute myocardial infarction and angina pectoris. The "currents of injury" created by a voltage gradient between the intact and damaged areas of the myocardium, negatively deflected the ECG vector during the diastolic phase, making the ST segment appear elevated during the systolic phase. This frog model of heart injury would be suitable to explain the mechanisms of ST segment changes observed in ischemic heart disease.

  2. Effects of a N(6)-disubstituted adenosine derivative on myocardial metabolism and ischemic stress following coronary occlusion.

    PubMed

    Kahles, H; Junggeburth, J; Lick, T; Schäfer, W; Kochsiek, K

    1987-10-01

    The effect of N(6)-phenyl-N(6)-allyladenosine (PAA, BM 11.189) on myocardial ischemic stress was evaluated in six open-chest mongrel dogs during repeated coronary occlusions of 3 min. Whereas there was not significant change in hemodynamic parameters before and during coronary occlusions after treatment, PAA reduced significantly epicardial ST-segment elevations (-34%) during ischemia and myocardial release of lactate (-43%), phosphate (-44%), and potassium (-48%) in the early reperfusion period. PAA lowered significantly arterial non esterified fatty acids and converted oxidative myocardial metabolism from lipid to predominantly carbohydrate utilization, reflected by a shift of cardiac respiratory quotient from 0.81 to 1.01. The beneficial effects of PAA on myocardial ischemic injury could be explained by an improved economy of oxidative myocardial energy supply in the jeopardized border zone of the ischemic myocardium.

  3. Biphasic effect of bimoclomol on calcium handling in mammalian ventricular myocardium

    PubMed Central

    Nánási, Péter P; Sárközi, Sándor; Szigeti, Gyula; Jóna, István; Szegedi, Csaba; Szabó, Ágnes; Bányász, Tamás; Magyar, János; Szigligeti, Péter; Körtvély, Ágnes; Csernoch, László; Kovács, László; Jednákovits, Andrea

    2000-01-01

    Concentration-dependent effects of bimoclomol, the novel heat shock protein coinducer, on intracellular calcium transients and contractility were studied in Langendorff-perfused guinea-pig hearts loaded with the fluorescent calcium indicator dye Fura-2. Bimoclomol had a biphasic effect on contractility: both peak left ventricular pressure and the rate of force development significantly increased at a concentration of 10 nM or higher. The maximal effect was observed between 0.1 and 1 μM, and the positive inotropic action disappeared by further increasing the concentration of bimoclomol. The drug increased systolic calcium concentration with a similar concentration-dependence. In contrast, diastolic calcium concentration increased monotonically in the presence of bimoclomol. Thus low concentrations of the drug (10–100 nM) increased, whereas high concentrations (10 μM) decreased the amplitude of intracellular calcium transients.Effects of bimoclomol on action potential configuration was studied in isolated canine ventricular myocytes. Action potential duration was increased at low (10 nM), unaffected at intermediate (0.1–1 μM) and decreased at high (10–100 μM) concentrations of the drug.In single canine sarcoplasmic calcium release channels (ryanodine receptor), incorporated into artificial lipid bilayer, bimoclomol significantly increased the open probability of the channel in the concentration range of 1–10 μM. The increased open probability was associated with increased mean open time. The effect of bimoclomol was again biphasic: the open probability decreased below the control level in the presence of 1 mM bimoclomol.Bimoclomol (10 μM–1 mM) had no significant effect on the rate of calcium uptake into sarcoplasmic reticulum vesicles of the dog, indicating that in vivo calcium reuptake might not substantially be affected by the drug.In conclusion, the positive inotropic action of bimoclomol is likely due to the activation of the

  4. Risk Stratification for Sudden Cardiac Death In Patients With Non-ischemic Dilated Cardiomyopathy

    PubMed Central

    Shekha, Karthik; Ghosh, Joydeep; Thekkoott, Deepak; Greenberg, Yisachar

    2005-01-01

    Non ischemic dilated cardiomyopathy (NIDCM) is a disorder of myocardium. It has varying etiologies. Albeit the varying etiologies of this heart muscle disorder, it presents with symptoms of heart failure, and rarely as sudden cardiac death (SCD). Manifestations of this disorder are in many ways similar to its counterpart, ischemic dilated cardiomyopathy (IDCM). A proportion of patients with NIDCM carries a grave prognosis and is prone to sudden cardiac death from sustained ventricular arrhythmias. Identification of this subgroup of patients who carry the risk of sudden cardiac death despite adequate medical management is a challenge .Yet another method is a blanket treatment of patients with this disorder with anti arrhythmic medications or anti tachyarrhythmia devices like implantable cardioverter defibrillators (ICD). However this modality of treatment could be a costly exercise even for affluent economies. In this review we try to analyze the existing data of risk stratification of NIDCM and its clinical implications in practice. PMID:16943952

  5. 9 CFR 113.305 - Canine Hepatitis and Canine Adenovirus Type 2 Vaccine.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... Type 2 Vaccine. 113.305 Section 113.305 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION... STANDARD REQUIREMENTS Live Virus Vaccines § 113.305 Canine Hepatitis and Canine Adenovirus Type 2 Vaccine. Canine Hepatitis Vaccine and Canine Adenovirus Type 2 Vaccine shall be prepared from virus-bearing...

  6. 9 CFR 113.305 - Canine Hepatitis and Canine Adenovirus Type 2 Vaccine.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... Type 2 Vaccine. 113.305 Section 113.305 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION... STANDARD REQUIREMENTS Live Virus Vaccines § 113.305 Canine Hepatitis and Canine Adenovirus Type 2 Vaccine. Canine Hepatitis Vaccine and Canine Adenovirus Type 2 Vaccine shall be prepared from virus-bearing...

  7. 9 CFR 113.202 - Canine Hepatitis and Canine Adenovirus Type 2 Vaccine, Killed Virus.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... Type 2 Vaccine, Killed Virus. 113.202 Section 113.202 Animals and Animal Products ANIMAL AND PLANT...; ORGANISMS AND VECTORS STANDARD REQUIREMENTS Killed Virus Vaccines § 113.202 Canine Hepatitis and Canine Adenovirus Type 2 Vaccine, Killed Virus. Canine Hepatitis and Canine Adenovirus Type 2 Vaccine, Killed...

  8. 9 CFR 113.202 - Canine Hepatitis and Canine Adenovirus Type 2 Vaccine, Killed Virus.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... Type 2 Vaccine, Killed Virus. 113.202 Section 113.202 Animals and Animal Products ANIMAL AND PLANT...; ORGANISMS AND VECTORS STANDARD REQUIREMENTS Killed Virus Vaccines § 113.202 Canine Hepatitis and Canine Adenovirus Type 2 Vaccine, Killed Virus. Canine Hepatitis and Canine Adenovirus Type 2 Vaccine, Killed...

  9. 9 CFR 113.202 - Canine Hepatitis and Canine Adenovirus Type 2 Vaccine, Killed Virus.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... Type 2 Vaccine, Killed Virus. 113.202 Section 113.202 Animals and Animal Products ANIMAL AND PLANT...; ORGANISMS AND VECTORS STANDARD REQUIREMENTS Killed Virus Vaccines § 113.202 Canine Hepatitis and Canine Adenovirus Type 2 Vaccine, Killed Virus. Canine Hepatitis and Canine Adenovirus Type 2 Vaccine, Killed...

  10. 9 CFR 113.305 - Canine Hepatitis and Canine Adenovirus Type 2 Vaccine.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... Type 2 Vaccine. 113.305 Section 113.305 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION... STANDARD REQUIREMENTS Live Virus Vaccines § 113.305 Canine Hepatitis and Canine Adenovirus Type 2 Vaccine. Canine Hepatitis Vaccine and Canine Adenovirus Type 2 Vaccine shall be prepared from virus-bearing...

  11. 9 CFR 113.202 - Canine Hepatitis and Canine Adenovirus Type 2 Vaccine, Killed Virus.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... Type 2 Vaccine, Killed Virus. 113.202 Section 113.202 Animals and Animal Products ANIMAL AND PLANT...; ORGANISMS AND VECTORS STANDARD REQUIREMENTS Killed Virus Vaccines § 113.202 Canine Hepatitis and Canine Adenovirus Type 2 Vaccine, Killed Virus. Canine Hepatitis and Canine Adenovirus Type 2 Vaccine, Killed...

  12. 9 CFR 113.305 - Canine Hepatitis and Canine Adenovirus Type 2 Vaccine.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... Type 2 Vaccine. 113.305 Section 113.305 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION... STANDARD REQUIREMENTS Live Virus Vaccines § 113.305 Canine Hepatitis and Canine Adenovirus Type 2 Vaccine. Canine Hepatitis Vaccine and Canine Adenovirus Type 2 Vaccine shall be prepared from virus-bearing...

  13. 9 CFR 113.202 - Canine Hepatitis and Canine Adenovirus Type 2 Vaccine, Killed Virus.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... Type 2 Vaccine, Killed Virus. 113.202 Section 113.202 Animals and Animal Products ANIMAL AND PLANT...; ORGANISMS AND VECTORS STANDARD REQUIREMENTS Killed Virus Vaccines § 113.202 Canine Hepatitis and Canine Adenovirus Type 2 Vaccine, Killed Virus. Canine Hepatitis and Canine Adenovirus Type 2 Vaccine, Killed...

  14. 9 CFR 113.305 - Canine Hepatitis and Canine Adenovirus Type 2 Vaccine.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... Type 2 Vaccine. 113.305 Section 113.305 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION... STANDARD REQUIREMENTS Live Virus Vaccines § 113.305 Canine Hepatitis and Canine Adenovirus Type 2 Vaccine. Canine Hepatitis Vaccine and Canine Adenovirus Type 2 Vaccine shall be prepared from virus-bearing...

  15. Myocardium and BMP signaling are required for endocardial differentiation.

    PubMed

    Palencia-Desai, Sharina; Rost, Megan S; Schumacher, Jennifer A; Ton, Quynh V; Craig, Michael P; Baltrunaite, Kristina; Koenig, Andrew L; Wang, Jinhu; Poss, Kenneth D; Chi, Neil C; Stainier, Didier Y R; Sumanas, Saulius

    2015-07-01

    Endocardial and myocardial progenitors originate in distinct regions of the anterior lateral plate mesoderm and migrate to the midline where they coalesce to form the cardiac tube. Endocardial progenitors acquire a molecular identity distinct from other vascular endothelial cells and initiate expression of specific genes such as nfatc1. Yet the molecular pathways and tissue interactions involved in establishing endocardial identity are poorly understood. The endocardium develops in tight association with cardiomyocytes. To test for a potential role of the myocardium in endocardial morphogenesis, we used two different zebrafish models deficient in cardiomyocytes: the hand2 mutant and a myocardial-specific genetic ablation method. We show that in hand2 mutants endocardial progenitors migrate to the midline but fail to assemble into a cardiac cone and do not express markers of differentiated endocardium. Endocardial differentiation defects were rescued by myocardial but not endocardial-specific expression of hand2. In metronidazole-treated myl7:nitroreductase embryos, myocardial cells were targeted for apoptosis, which resulted in the loss of endocardial nfatc1 expression. However, endocardial cells were present and retained expression of general vascular endothelial markers. We further identified bone morphogenetic protein (BMP) as a candidate myocardium-derived signal required for endocardial differentiation. Chemical and genetic inhibition of BMP signaling at the tailbud stage resulted in severe inhibition of endocardial differentiation while there was little effect on myocardial development. Heat-shock-induced bmp2b expression rescued endocardial nfatc1 expression in hand2 mutants and in myocardium-depleted embryos. Our results indicate that the myocardium is crucial for endocardial morphogenesis and differentiation, and identify BMP as a signal involved in endocardial differentiation.

  16. Cardioprotection of ischemic preconditioning in rats involves upregulating adiponectin.

    PubMed

    Wang, Hui; Wu, Wenjing; Duan, Jun; Ma, Ming; Kong, Wei; Ke, Yuannan; Li, Gang; Zheng, Jingang

    2017-02-20

    It has been reported that ischemic preconditioning (IPC) and adiponectin (APN) are cardioprotective in many cardiovascular disorders. However, whether APN mediates the effect of IPC on myocardial injury has not been elucidated. This study was conducted to investigate whether IPC affects myocardial ischemic injury by increasing APN expression. Male adult rats with cardiac knockdowns of APN and its receptors via intramyocardial small-interfering RNA injection were subjected to IPC and then myocardial infarction (MI) at 24 h post-IPC. Globular APN (gAd) was injected at 10 min before MI. APN mRNA and protein levels in myocardium as well as the plasma APN concentration were markedly high at 6 and 12 h after IPC. IPC ameliorated myocardial injury as evidenced by improved cardiac functions and a reduced infarct size. Compared with the control MI group, rats in the IPC + MI group had elevated levels of left ventricular ejection fraction and fractional shortening, and a smaller MI size (P<0.05). However, the aforementioned protective effects were ameliorated in the absence of APN and APN receptors, followed by inhibition of AMP-activated protein kinase (AMPK) phosphorylation, but reversed by gAd treatment in wild-type rats, and AMPK phosphorylation increased (P<0.05). Overall, our results suggest that the cardioprotective effects of IPC are partially due to upregulation of APN, and provide a further insight into IPC-mediated signaling effects.

  17. The Clinical Status of Stem Cell Therapy for Ischemic Cardiomyopathy.

    PubMed

    Wang, Xianyun; Zhang, Jun; Zhang, Fan; Li, Jing; Li, Yaqi; Tan, Zirui; Hu, Jie; Qi, Yixin; Li, Quanhai; Yan, Baoyong

    2015-01-01

    Ischemic cardiomyopathy (ICM) is becoming a leading cause of morbidity and mortality in the whole world. Stem cell-based therapy is emerging as a promising option for treatment of ICM. Several stem cell types including cardiac-derived stem cells (CSCs), bone marrow-derived stem cells, mesenchymal stem cells (MSCs), skeletal myoblasts (SMs), and CD34(+) and CD 133(+) stem cells have been applied in clinical researches. The clinical effect produced by stem cell administration in ICM mainly depends on the transdifferentiation and paracrine effect. One important issue is that low survival and residential rate of transferred stem cells in the infracted myocardium blocks the effective advances in cardiac improvement. Many other factors associated with the efficacy of cell replacement therapy for ICM mainly including the route of delivery, the type and number of stem cell infusion, the timing of injection, patient's physical condition, the particular microenvironment onto which the cells are delivered, and clinical condition remain to be addressed. Here we provide an overview of the pros and cons of these transferred cells and discuss the current state of their therapeutic potential. We believe that stem cell translation will be an ideal option for patients following ischemic heart disease in the future.

  18. Efficacy of coronary angioplasty for the treatment of hibernating myocardium

    PubMed Central

    Fath-Ordoubadi, F; Beatt, K; Spyrou, N; Camici, P

    1999-01-01

    OBJECTIVES—To determine the efficacy of coronary angioplasty as the sole method of revascularisation in patients with coronary artery disease and chronically dysfunctional but viable myocardium (hibernating myocardium), and to assess the effect of restenosis on functional outcome.
DESIGN AND PATIENTS—24 consecutive patients with hibernating myocardium were studied. Positron emission tomography was used to assess myocardial viability, blood flow, and flow reserve. One patient refused angioplasty, one had bypass surgery, and one died while waiting for an elective procedure. The procedure failed in three patients. The remaining 18 patients had repeat echocardiography, 15 had repeat coronary angiography, and nine had repeat assessments of blood flow and flow reserve at mean (SD) 17 (2) weeks after angioplasty. In three patients restenosis was documented.
RESULTS—The wall motion score index in the revascularised territories improved from 1.71 (0.37) to 1.34 (0.47) (p = 0.008). Thirty of 51 dysfunctional segments improved in territories without restenosis compared with three of 14 in restenosed territories (p = 0.001). Hibernating and normal segments had comparable flows (0.82 (0.26) v 0.89 (0.24) ml/min/g; NS) while flow reserve was lower in hibernating segments (1.55 (0.68) v 2.07 (1.08); p = 0.03). In segments without restenosis flow reserve improved from 2.03 (1.25) to 2.33 (1.4) (p = 0.03). Sensitivity, specificity, and positive and negative predictive accuracy of the viability study were 97%, 77%, 82%, and 96%, respectively. After excluding patients with restenosis, specificity and positive predictive accuracy improved to 90% and 93%.
CONCLUSIONS—Angioplasty improves function in hibernating myocardium, and restenosis prevents recovery; hibernating myocardium is characterised by an impairment of flow reserve; restenosis affects the diagnostic accuracy of viability studies.


Keywords: coronary artery disease; percutaneous

  19. Ischemic mitral valve prolapse

    PubMed Central

    Cristiano, Spadaccio; Nenna, Antonio; Chello, Massimo

    2016-01-01

    Ischemic mitral prolapse (IMP) is a pathologic entity encountered in about one-third among the patients undergoing surgery for ischemic mitral regurgitation (IMR). IMP is generally the result of a papillary muscle injury consequent to myocardial, but the recent literature is progressively unveiling a more complex pathogenesis. The mechanisms underlying its development regards the impairment of one or more components of the mitral apparatus, which comprises the annulus, the chordae tendineae, the papillary muscle and the left ventricular wall. IMP is not only a disorder of valvular function, but also entails coexistent aspects of a geometric disturbance of the mitral valve configuration and of the left ventricular function and dimension and a correct understanding of all these aspects is crucial to guide and tailor the correct therapeutic strategy to be adopted. Localization of prolapse, anatomic features of the prolapsed leaflets and the subvalvular apparatus should be carefully evaluated as also constituting the major determinants defining patient’s outcomes. This review will summarize our current understanding of the pathophysiology and clinical evidence on IMP with a particular focus on the surgical treatment. PMID:28149574

  20. High expression of arachidonate 15-lipoxygenase and proinflammatory markers in human ischemic heart tissue

    SciTech Connect

    Magnusson, Lisa U.; Lundqvist, Annika; Asp, Julia; Synnergren, Jane; Johansson, Cecilia Thalen; Palmqvist, Lars; Jeppsson, Anders; Hulten, Lillemor Mattsson

    2012-07-27

    Highlights: Black-Right-Pointing-Pointer We found a 17-fold upregulation of ALOX15 in the ischemic heart. Black-Right-Pointing-Pointer Incubation of human muscle cells in hypoxia showed a 22-fold upregulation of ALOX15. Black-Right-Pointing-Pointer We observed increased levels of proinflammatory markers in ischemic heart tissue. Black-Right-Pointing-Pointer Suggesting a link between ischemia and inflammation in ischemic heart biopsies. -- Abstract: A common feature of the ischemic heart and atherosclerotic plaques is the presence of hypoxia (insufficient levels of oxygen in the tissue). Hypoxia has pronounced effects on almost every aspect of cell physiology, and the nuclear transcription factor hypoxia inducible factor-1{alpha} (HIF-1{alpha}) regulates adaptive responses to low concentrations of oxygen in mammalian cells. In our recent work, we observed that hypoxia increases the proinflammatory enzyme arachidonate 15-lipoxygenase (ALOX15B) in human carotid plaques. ALOX15 has recently been shown to be present in the human myocardium, but the effect of ischemia on its expression has not been investigated. Here we test the hypothesis that ischemia of the heart leads to increased expression of ALOX15, and found an almost 2-fold increase in HIF-1{alpha} mRNA expression and a 17-fold upregulation of ALOX15 mRNA expression in the ischemic heart biopsies from patients undergoing coronary bypass surgery compared with non ischemic heart tissue. To investigate the effect of low oxygen concentration on ALOX15 we incubated human vascular muscle cells in hypoxia and showed that expression of ALOX15 increased 22-fold compared with cells incubated in normoxic conditions. We also observed increased mRNA levels of proinflammatory markers in ischemic heart tissue compared with non-ischemic controls. In summary, we demonstrate increased ALOX15 in human ischemic heart biopsies. Furthermore we demonstrate that hypoxia increases ALOX15 in human muscle cells. Our results yield

  1. Genomic Sequence of Canine Papillomavirus 19

    PubMed Central

    Tisza, Michael J.; Yuan, Hang; Schlegel, Richard

    2016-01-01

    It is generally assumed that individual papillomas (warts) are caused by infection with individual papillomavirus types. Deep sequencing of virions extracted from a canine oral papilloma revealed the presence of canine papillomavirus 1 (CPV1), CPV2, and a novel canine papillomavirus, CPV19. This suggests that papillomas sometimes harbor multiple viral species. PMID:27932663

  2. Effect of thymol on calcium handling in mammalian ventricular myocardium.

    PubMed

    Szentandrássy, Norbert; Szigeti, Gyula; Szegedi, Csaba; Sárközi, Sándor; Magyar, János; Bányász, Tamás; Csernoch, László; Kovács, László; Nánási, Péter P; Jóna, István

    2004-01-02

    Concentration-dependent effects of thymol on calcium handling were studied in canine and guinea pig cardiac preparations (Langendorff-perfused guinea pig hearts, canine ventricular trabeculae, canine sarcoplasmic reticular vesicles and single ryanodine receptors). Thymol induced a concentration-dependent negative inotropic action in both canine and guinea pig preparations (EC(50) = 297 +/- 12 microM in dog). However, low concentrations of thymol reduced intracellular calcium transients in guinea pig hearts without decreasing contractility. At higher concentrations both calcium transients and contractions were suppressed. In canine sarcoplasmic reticular vesicles thymol induced rapid release of calcium (V(max) = 0.47 +/- 0.04 nmol s(-1), EC(50) = 258 +/- 21 microM, Hill coefficient = 3.0 +/- 0.54), and decreased the activity of the calcium pump (EC(50) = 253 +/- 4.7 microM, Hill coefficient = 1.62 +/- 0.05). Due to the less sharp concentration-dependence of the ATPase inhibition, this effect was significant from 50 microM, whereas the thymol-induced calcium release only from 100 microM. In single ryanodine receptors incorporated into artificial lipid bilayer thymol induced long lasting openings, having mean open times increased with 3 orders of magnitude, however, the specific conductance of the channel remained unaltered. This effect of thymol was not voltage-dependent and failed to prevent the binding of ryanodine. In conclusion, the negative inotropic action of thymol can be explained by reduction in calcium content of the sarcoplasmic reticulum due to the combination of the thymol-induced calcium release and inhibition of the calcium pump. The calcium-sensitizer effect, observed at lower thymol concentrations, indicates that thymol is likely to interact with the contractile machinery also.

  3. Intracoronary Delivery of Mitochondria to the Ischemic Heart for Cardioprotection

    PubMed Central

    Cowan, Douglas B.; Yao, Rouan; Akurathi, Vamsidhar; Snay, Erin R.; Thedsanamoorthy, Jerusha K.; Zurakowski, David; Ericsson, Maria; Friehs, Ingeborg; Wu, Yaotang; Levitsky, Sidney; del Nido, Pedro J.; Packard, Alan B.

    2016-01-01

    We have previously shown that transplantation of autologously derived, respiration-competent mitochondria by direct injection into the heart following transient ischemia and reperfusion enhances cell viability and contractile function. To increase the therapeutic potential of this approach, we investigated whether exogenous mitochondria can be effectively delivered through the coronary vasculature to protect the ischemic myocardium and studied the fate of these transplanted organelles in the heart. Langendorff-perfused rabbit hearts were subjected to 30 minutes of ischemia and then reperfused for 10 minutes. Mitochondria were labeled with 18F-rhodamine 6G and iron oxide nanoparticles. The labeled mitochondria were either directly injected into the ischemic region or delivered by vascular perfusion through the coronary arteries at the onset of reperfusion. These hearts were used for positron emission tomography, microcomputed tomography, and magnetic resonance imaging with subsequent microscopic analyses of tissue sections to confirm the uptake and distribution of exogenous mitochondria. Injected mitochondria were localized near the site of delivery; while, vascular perfusion of mitochondria resulted in rapid and extensive dispersal throughout the heart. Both injected and perfused mitochondria were observed in interstitial spaces and were associated with blood vessels and cardiomyocytes. To determine the efficacy of vascular perfusion of mitochondria, an additional group of rabbit hearts were subjected to 30 minutes of regional ischemia and reperfused for 120 minutes. Immediately following regional ischemia, the hearts received unlabeled, autologous mitochondria delivered through the coronary arteries. Autologous mitochondria perfused through the coronary vasculature significantly decreased infarct size and significantly enhanced post-ischemic myocardial function. In conclusion, the delivery of mitochondria through the coronary arteries resulted in their rapid

  4. BRAF Mutations in Canine Cancers.

    PubMed

    Mochizuki, Hiroyuki; Kennedy, Katherine; Shapiro, Susan G; Breen, Matthew

    2015-01-01

    Activating mutations of the BRAF gene lead to constitutive activation of the MAPK pathway. Although many human cancers carry the mutated BRAF gene, this mutation has not yet been characterized in canine cancers. As human and canine cancers share molecular abnormalities, we hypothesized that BRAF gene mutations also exist in canine cancers. To test this hypothesis, we sequenced the exon 15 of BRAF, mutation hot spot of the gene, in 667 canine primary tumors and 38 control tissues. Sequencing analysis revealed that a single nucleotide T to A transversion at nucleotide 1349 occurred in 64 primary tumors (9.6%), with particularly high frequency in prostatic carcinoma (20/25, 80%) and urothelial carcinoma (30/45, 67%). This mutation results in the amino acid substitution of glutamic acid for valine at codon 450 (V450E) of canine BRAF, corresponding to the most common BRAF mutation in human cancer, V600E. The evolutional conservation of the BRAF V600E mutation highlights the importance of MAPK pathway activation in neoplasia and may offer opportunity for molecular diagnostics and targeted therapeutics for dogs bearing BRAF-mutated cancers.

  5. Effects of tacrolimus on action potential configuration and transmembrane ion currents in canine ventricular cells.

    PubMed

    Szabó, László; Szentandrássy, Norbert; Kistamás, Kornél; Hegyi, Bence; Ruzsnavszky, Ferenc; Váczi, Krisztina; Horváth, Balázs; Magyar, János; Bányász, Tamás; Pál, Balázs; Nánási, Péter P

    2013-03-01

    Tacrolimus is a commonly used immunosuppressive agent which causes cardiovascular complications, e.g., hypertension and hypertrophic cardiomyopathy. In spite of it, there is little information on the cellular cardiac effects of the immunosuppressive agent tacrolimus in larger mammals. In the present study, therefore, the concentration-dependent effects of tacrolimus on action potential morphology and the underlying ion currents were studied in canine ventricular cardiomyocytes. Standard microelectrode, conventional whole cell patch clamp, and action potential voltage clamp techniques were applied in myocytes enzymatically dispersed from canine ventricular myocardium. Tacrolimus (3-30 μM) caused a concentration-dependent reduction of maximum velocity of depolarization and repolarization, action potential amplitude, phase-1 repolarization, action potential duration, and plateau potential, while no significant change in the resting membrane potential was observed. Conventional voltage clamp experiments revealed that tacrolimus concentrations ≥3 μM blocked a variety of ion currents, including I(Ca), I(to), I(K1), I(Kr), and I(Ks). Similar results were obtained under action potential voltage clamp conditions. These effects of tacrolimus developed rapidly and were fully reversible upon washout. The blockade of inward currents with the concomitant shortening of action potential duration in canine myocytes is the opposite of those observed previously with tacrolimus in small rodents. It is concluded that although tacrolimus blocks several ion channels at higher concentrations, there is no risk of direct interaction with cardiac ion channels when applying tacrolimus in therapeutic concentrations.

  6. Podoplanin Expression in Canine Melanoma.

    PubMed

    Ogasawara, Satoshi; Honma, Ryusuke; Kaneko, Mika K; Fujii, Yuki; Kagawa, Yumiko; Konnai, Satoru; Kato, Yukinari

    2016-12-01

    A type I transmembrane protein, podoplanin (PDPN), is expressed in several normal cells such as lymphatic endothelial cells or pulmonary type I alveolar cells. We recently demonstrated that anticanine PDPN monoclonal antibody (mAb), PMab-38, recognizes canine PDPN of squamous cell carcinomas, but does not react with lymphatic endothelial cells. Herein, we investigated whether PMab-38 reacts with canine melanoma. PMab-38 reacted with 90% of melanoma cells (9/10 cases) using immunohistochemistry. Of interest, PMab-38 stained the lymphatic endothelial cells and cancer-associated fibroblasts in melanoma tissues, although it did not stain any lymphatic endothelial cells in normal tissues. PMab-38 could be useful for uncovering the function of PDPN in canine melanomas.

  7. Canine "honing" in Australopithecus afarensis.

    PubMed

    Greenfield, L O

    1990-06-01

    The maxillary canines of Australopithecus afarensis show a distal wear facet that extends from the apex of the crown to a point near the distal cingulum. Although these facets bear a superficial resemblance to the honing facets found on the projecting portions of the canines of other anthropoids, a more detailed examination provided in this paper shows that they are not homologous or functionally equivalent. The facets are not related to the use of the maxillary canine as a weapon or as an additional masticatory surface. Instead, their presence in A. afarensis represented a blunting or dulling of the posterior edge of C so that its occlusion with P3 would be consistent with cheek tooth occlusion.

  8. Podoplanin Expression in Canine Melanoma

    PubMed Central

    Ogasawara, Satoshi; Honma, Ryusuke; Kaneko, Mika K.; Fujii, Yuki; Kagawa, Yumiko; Konnai, Satoru

    2016-01-01

    A type I transmembrane protein, podoplanin (PDPN), is expressed in several normal cells such as lymphatic endothelial cells or pulmonary type I alveolar cells. We recently demonstrated that anticanine PDPN monoclonal antibody (mAb), PMab-38, recognizes canine PDPN of squamous cell carcinomas, but does not react with lymphatic endothelial cells. Herein, we investigated whether PMab-38 reacts with canine melanoma. PMab-38 reacted with 90% of melanoma cells (9/10 cases) using immunohistochemistry. Of interest, PMab-38 stained the lymphatic endothelial cells and cancer-associated fibroblasts in melanoma tissues, although it did not stain any lymphatic endothelial cells in normal tissues. PMab-38 could be useful for uncovering the function of PDPN in canine melanomas. PMID:27918691

  9. Repetitive stimulation of autophagy-lysosome machinery by intermittent fasting preconditions the myocardium to ischemia-reperfusion injury.

    PubMed

    Godar, Rebecca J; Ma, Xiucui; Liu, Haiyan; Murphy, John T; Weinheimer, Carla J; Kovacs, Attila; Crosby, Seth D; Saftig, Paul; Diwan, Abhinav

    2015-01-01

    Autophagy, a lysosomal degradative pathway, is potently stimulated in the myocardium by fasting and is essential for maintaining cardiac function during prolonged starvation. We tested the hypothesis that intermittent fasting protects against myocardial ischemia-reperfusion injury via transcriptional stimulation of the autophagy-lysosome machinery. Adult C57BL/6 mice subjected to 24-h periods of fasting, every other day, for 6 wk were protected from in-vivo ischemia-reperfusion injury on a fed day, with marked reduction in infarct size in both sexes as compared with nonfasted controls. This protection was lost in mice heterozygous null for Lamp2 (coding for lysosomal-associated membrane protein 2), which demonstrate impaired autophagy in response to fasting with accumulation of autophagosomes and SQSTM1, an autophagy substrate, in the heart. In lamp2 null mice, intermittent fasting provoked progressive left ventricular dilation, systolic dysfunction and hypertrophy; worsening cardiomyocyte autophagosome accumulation and lack of protection to ischemia-reperfusion injury, suggesting that intact autophagy-lysosome machinery is essential for myocardial homeostasis during intermittent fasting and consequent ischemic cardioprotection. Fasting and refeeding cycles resulted in transcriptional induction followed by downregulation of autophagy-lysosome genes in the myocardium. This was coupled with fasting-induced nuclear translocation of TFEB (transcription factor EB), a master regulator of autophagy-lysosome machinery; followed by rapid decline in nuclear TFEB levels with refeeding. Endogenous TFEB was essential for attenuation of hypoxia-reoxygenation-induced cell death by repetitive starvation, in neonatal rat cardiomyocytes, in-vitro. Taken together, these data suggest that TFEB-mediated transcriptional priming of the autophagy-lysosome machinery mediates the beneficial effects of fasting-induced autophagy in myocardial ischemia-reperfusion injury.

  10. Repetitive stimulation of autophagy-lysosome machinery by intermittent fasting preconditions the myocardium to ischemia-reperfusion injury

    PubMed Central

    Godar, Rebecca J; Ma, Xiucui; Liu, Haiyan; Murphy, John T; Weinheimer, Carla J; Kovacs, Attila; Crosby, Seth D; Saftig, Paul; Diwan, Abhinav

    2015-01-01

    Autophagy, a lysosomal degradative pathway, is potently stimulated in the myocardium by fasting and is essential for maintaining cardiac function during prolonged starvation. We tested the hypothesis that intermittent fasting protects against myocardial ischemia-reperfusion injury via transcriptional stimulation of the autophagy-lysosome machinery. Adult C57BL/6 mice subjected to 24-h periods of fasting, every other day, for 6 wk were protected from in-vivo ischemia-reperfusion injury on a fed day, with marked reduction in infarct size in both sexes as compared with nonfasted controls. This protection was lost in mice heterozygous null for Lamp2 (coding for lysosomal-associated membrane protein 2), which demonstrate impaired autophagy in response to fasting with accumulation of autophagosomes and SQSTM1, an autophagy substrate, in the heart. In lamp2 null mice, intermittent fasting provoked progressive left ventricular dilation, systolic dysfunction and hypertrophy; worsening cardiomyocyte autophagosome accumulation and lack of protection to ischemia-reperfusion injury, suggesting that intact autophagy-lysosome machinery is essential for myocardial homeostasis during intermittent fasting and consequent ischemic cardioprotection. Fasting and refeeding cycles resulted in transcriptional induction followed by downregulation of autophagy-lysosome genes in the myocardium. This was coupled with fasting-induced nuclear translocation of TFEB (transcription factor EB), a master regulator of autophagy-lysosome machinery; followed by rapid decline in nuclear TFEB levels with refeeding. Endogenous TFEB was essential for attenuation of hypoxia-reoxygenation-induced cell death by repetitive starvation, in neonatal rat cardiomyocytes, in-vitro. Taken together, these data suggest that TFEB-mediated transcriptional priming of the autophagy-lysosome machinery mediates the beneficial effects of fasting-induced autophagy in myocardial ischemia-reperfusion injury. PMID:26103523

  11. Repeated sauna therapy attenuates ventricular remodeling after myocardial infarction in rats by increasing coronary vascularity of noninfarcted myocardium.

    PubMed

    Sobajima, Mitsuo; Nozawa, Takashi; Shida, Takuya; Ohori, Takashi; Suzuki, Takayuki; Matsuki, Akira; Inoue, Hiroshi

    2011-08-01

    Repeated sauna therapy (ST) increases endothelial nitric oxide synthase (eNOS) activity and improves cardiac function in heart failure as well as peripheral blood flow in ischemic limbs. The present study investigates whether ST can increase coronary vascularity and thus attenuate cardiac remodeling after myocardial infarction (MI). We induced MI by ligating the left coronary artery of Wistar rats. The rats were placed in a far-infrared dry sauna at 41°C for 15 min and then at 34°C for 20 min once daily for 4 wk. Cardiac hemodynamic, histopathological, and gene analyses were performed. Despite the similar sizes of MI between the ST and non-ST groups (51.4 ± 0.3 vs. 51.1 ± 0.2%), ST reduced left ventricular (LV) end-diastolic (9.7 ± 0.4 vs. 10.7 ± 0.5 mm, P < 0.01) and end-systolic (8.6 ± 0.5 vs. 9.6 ± 0.6 mm, P < 0.01) dimensions and attenuated MI-induced increases in LV end-diastolic pressure. Cross-sectional areas of cardiomyocytes were smaller in ST rats and associated with a significant reduction in myocardial atrial natriuretic peptide mRNA levels. Vascular density was reduced in the noninfarcted myocardium of non-ST rats, and the density of cells positive for CD31 and for α-smooth muscle actin was decreased. These decreases were attenuated in ST rats compared with non-ST rats and associated with increases in myocardial eNOS and vascular endothelial growth factor mRNA levels. In conclusion, ST attenuates cardiac remodeling after MI, at least in part, through improving coronary vascularity in the noninfarcted myocardium. Repeated ST might serve as a novel noninvasive therapy for patients with MI.

  12. Direct effects of smoking on the heart: silent ischemic disturbances of coronary flow

    SciTech Connect

    Deanfield, J.E.; Shea, M.J.; Wilson, R.A.; Horlock, P.; de Landsheere, C.M.; Selwyn, A.P.

    1986-05-01

    Cigarette smoking is strongly associated with ischemic heart disease and acute coronary events. The effect of smoking a single cigarette on regional myocardial perfusion was studied in 13 chronic smokers with typical stable angina pectoris using positron emission tomography and rubidium-82 (/sup 82/Rb). Findings were compared with the effects of physical exercise. After exercise, 8 patients (61%) had angina, ST depression and abnormal regional myocardial perfusion. Uptake of /sup 82/Rb increased from 49 +/- 8 to 60 +/- 7 in remote myocardium, but decreased from 46 +/- 3 to 37 +/- 5 in an ischemic area. The remaining 5 patients (39%) had homogeneous increases in /sup 82/Rb uptake without angina or ST depression. After smoking, 6 of the 8 patients with positive exercise test responses had a decrease in /sup 82/Rb uptake, from 47 +/- 3 to 35 +/- 6 in the same segment of myocardium affected during exercise. However, in contrast to exercise, the events during smoking were largely silent. The absolute decreases in regional /sup 82/Rb uptake after smoking occurred at significantly lower levels of myocardial oxygen demand than after exercise. This suggests that an impairment of coronary blood supply is responsible. Thus, in smokers with coronary artery disease, each cigarette can cause profound silent disturbances of regional myocardial perfusion that are likely to occur frequently during daily life. Such repeated insults may represent an important mechanism linking smoking with coronary events.

  13. Mandibular canine index in establishing sex identity.

    PubMed

    Yadav, Shishir; Nagabhushana, D; Rao, B Balaji; Mamatha, G P

    2002-01-01

    An investigation study on sex identity through mandibular canine index directed to detect sexual dimorphism using the Mesio-Distal width of mandibular permanent canines and inter canine and inter canine arch width in the mandible was conducted in the Department of Oral Medicine and Radiology, Bapuji Dental College and Hospital, Davangere. 360 patients were subjected to the mesio-distal measurement and inter canine arch width. Males were detected correctly in 83.3% and in females 81%. They were statistically significant and the related literatures reviewed.

  14. [Cerebrolysin for acute ischemic stroke].

    PubMed

    iganshina, L E; Abakumova, T R

    2013-01-01

    The review discusses existing evidence of benefits and risks of cerebrolysin--a mixture of low-molecular-weight peptides and amino acids derived from pigs' brain tissue with proposed neuroprotective and neurotrophic properties, for acute ischemic stroke. The review presents results of systematic search and analysis of randomised clinical trials comparing cerebrolysin with placebo in patients with acute ischemic stroke. Only one trial was selected as meeting quality criteria. No difference in death and adverse events between cerebrolysin and placebo was established. The authors conclude about insufficiency of evidence to evaluate the effect of cerebrolysin on survival and dependency in people with acute ischemic stroke.

  15. Canine tooth size variability in primates.

    PubMed

    Beauchamp, G

    1989-01-01

    I present an analysis of canine tooth size variability in male and female primates. The coefficient of variation (CV = SD X 100/mean) as an index of canine size variability proved to be dependent on mean canine size in males and, to a lower extent, in females. Therefore, variability tends to increase with increasing values of mean canine size. Using residuals from the regression of log SD on log mean canine size in male and female primates, I analysed the contribution of diet, habitat and mating system to canine size variability. Habitat and mating system are known to influence to a certain extent the degree of sexual dimorphism in canine size. Given the well-known relationship between sexual dimorphism and phenotypic variability, it was suggested that these factors might influence variability in canine size. Everything else being equal, males of polygynous species are characterized by more variable canine sizes than males of monogamous species. Habitat and diet did not contribute to the level of variability observed in either males or females. It is proposed that a high level of variability in canine size may be related to the likelihood that enlarged canines evolved as a result of male-male competition for mates in polygynous species.

  16. The effects of exposure to electromagnetic field on rat myocardium.

    PubMed

    Kiray, Amac; Tayefi, Hamid; Kiray, Muge; Bagriyanik, Husnu Alper; Pekcetin, Cetin; Ergur, Bekir Ugur; Ozogul, Candan

    2013-06-01

    Exposure to electromagnetic fields (EMFs) causes increased adverse effects on biological systems. The aim of this study was to investigate the effects of EMF on heart tissue by biochemical and histomorphological evaluations in EMF-exposed adult rats. In this study, 28 male Wistar rats weighing 200-250 g were used. The rats were divided into two groups: sham group (n = 14) and EMF group (n = 14). Rats in sham group were exposed to same conditions as the EMF group except the exposure to EMF. Rats in EMF group were exposed to a 50-Hz EMF of 3 mT for 4 h/day and 7 days/week for 2 months. After 2 months of exposure, rats were killed; the hearts were excised and evaluated. Determination of oxidative stress parameters was performed spectrophotometrically. To detect apoptotic cells, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining and caspase-3 immunohistochemistry were performed. In EMF-exposed group, levels of lipid peroxidation significantly increased and activities of superoxide dismutase and glutathione peroxidase decreased compared with sham group. The number of TUNEL-positive cells and caspase-3 immunoreactivity increased in EMF-exposed rats compared with sham. Under electron microscopy, there were mitochondrial degeneration, reduction in myofibrils, dilated sarcoplasmic reticulum and perinuclear vacuolization in EMF-exposed rats. In conclusion, the results show that the exposure to EMF causes oxidative stress, apoptosis and morphologic damage in myocardium of adult rats. The results of our study indicate that EMF-related changes in rat myocardium could be the result of increased oxidative stress. Further studies are needed to demonstrate whether the exposure to EMF can induce adverse effects on myocardium.

  17. Comparative Efficacy of Intracoronary Allogeneic Mesenchymal Stem Cells and Cardiosphere-Derived Cells in Swine with Hibernating Myocardium

    PubMed Central

    Weil, Brian R.; Suzuki, Gen; Leiker, Merced M.; Fallavollita, James A.; Canty, John M.

    2015-01-01

    Rationale Allogeneic bone marrow-derived mesenchymal stem cells (MSCs) and cardiosphere-derived cells (CDCs) have each entered clinical trials but a direct comparison of these cell types has not been performed in a large animal model of hibernating myocardium. Objective Using completely blinded methodology, compare the efficacy of global intracoronary allogeneic MSCs (icMSCs, ~35×106) and CDCs (icCDCs, ~35×106) vs. vehicle in cyclosporine-immunosuppressed swine with a chronic LAD stenosis (n=26). Methods and Results Studies began 3-months after instrumentation when wall-thickening (%WT) was reduced (LAD%WT 38±11% (mean ± SD) vs. 83±26% in remote, p<0.01) and similar among groups. Four-weeks after treatment, LAD%WT increased similarly following icCDCs and icMSCs, while it remained depressed in vehicle-treated controls (icMSCs: 51±13%; icCDCs: 51±17%; vehicle: 34±3%, treatments p<0.05 vs. vehicle). There was no change in myocardial perfusion. Both icMSCs and icCDCs increased LAD myocyte nuclear density (icMSCs: 1601±279 nuclei/mm2, icCDCs: 1569±294 nuclei/mm2, vehicle: 973±181 nuclei/mm2, treatments p<0.05 vs. vehicle) and reduced myocyte diameter (icMSCs: 16.4±1.5 μm, icCDCs: 16.8±1.2 μm, vehicle: 20.2±3.7 μm, treatments p<0.05 vs. vehicle) to the same extent. Similar changes in myocyte nuclear density and diameter were observed in the remote region of cell-treated animals. Cell fate analysis using Y-FISH demonstrated rare cells from sex-mismatched donors. Conclusions Allogeneic icMSCs and icCDCs exhibit comparable therapeutic efficacy in a large animal model of hibernating myocardium. Both cell types produced equivalent increases in regional function and stimulated myocyte regeneration in ischemic and remote myocardium. The activation of endogenous myocyte proliferation and regression of myocyte cellular hypertrophy support a common mechanism of cardiac repair. PMID:26271689

  18. Canine and feline colostrum.

    PubMed

    Chastant-Maillard, S; Aggouni, C; Albaret, A; Fournier, A; Mila, H

    2016-11-30

    Puppy and kitten survival over the first weeks is particularly dependent on colostrum, a specific secretion of the mammary gland produced during the first 2 days post-partum. Colostrum is a source of nutrients and immunoglobulins. It also contributes to the digestive tract maturation. Colostrum differentiates from milk mainly based on its concentration in immunoglobulins G: 20-30 g/L in dog colostrum, 40-50 g/L in cats' vs <1 g/L in milk. IgG concentration rapidly drops after parturition (-50% in 24 hr). Immune quality of colostrum is highly variable between bitches, with no relationship with maternal blood IgG level, dam's age, breed size or litter size. In addition to systemic immune protection, colostrum also plays a major role for local digestive protection, due to IgA, lysozyme, lactoferrin, white blood cells and various cytokines. Energetic concentration of canine and feline colostrum is not superior to that of mature milk. It depends on colostrum fat concentration and is affected by breed size (higher in breeds <10 kg adult body weight). As puppies and kittens are almost agammaglobulinemic at birth, transfer of IgG from their digestive tract into their bloodstream is crucial for their survival, IgG absorption ending at 12-16 hr after birth. Energetic supply over the two first days of life, as evidenced by growth rate over the two first days of life, also affects risk of neonatal mortality. Early and sufficient suckling of colostrum is thus the very first care to be provided to newborns for their later health and survival.

  19. Drug-induced changes in action potential duration are proportional to action potential duration in rat ventricular myocardium.

    PubMed

    Bárándi, László; Harmati, Gábor; Horváth, Balázs; Szentandrássy, Norbert; Magyar, János; Varró, András; Nánási, Péter P; Bányász, Tamás

    2010-09-01

    Several cardioactive agents exhibit direct or reverse rate-dependent effects on action potential duration (APD) depending on the experimental conditions. Recently, a new theory has been proposed, suggesting that the reverse rate-dependent mode of drug-action may be a common property of canine, rabbit, guinea pig and human cardiac tissues, and this phenomenon is based on the dependence of drug-action on baseline APD. The aim of the present work was to examine the limitations of this hypothesis by studying the APD lengthening effect of K(+) channel blockers and the APD shortening effect of Ca(2+) channel blockers during the electrical restitution process of rat ventricular action potentials. Rat ventricular muscle was chosen because it has a set of ion currents markedly different from those of other species, its APD is shorter by one order of magnitude than that of the "plateau-forming" larger mammals, and most importantly, its APD increases at higher heart rates - opposite to many other species. The restitution of APD was studied as a function of the diastolic interval, a parameter indicating the proximity of action potentials. It was found that drug-induced APD changes in rat myocardium are proportional with the pre-drug value of APD but not with the diastolic interval, indicating that not the proximity of consecutive action potentials, but the baseline APD itself may determine the magnitude of drug-induced APD changes.

  20. Preterm Hypoxic–Ischemic Encephalopathy

    PubMed Central

    Gopagondanahalli, Krishna Revanna; Li, Jingang; Fahey, Michael C.; Hunt, Rod W.; Jenkin, Graham; Miller, Suzanne L.; Malhotra, Atul

    2016-01-01

    Hypoxic–ischemic encephalopathy (HIE) is a recognizable and defined clinical syndrome in term infants that results from a severe or prolonged hypoxic–ischemic episode before or during birth. However, in the preterm infant, defining hypoxic–ischemic injury (HII), its clinical course, monitoring, and outcomes remains complex. Few studies examine preterm HIE, and these are heterogeneous, with variable inclusion criteria and outcomes reported. We examine the available evidence that implies that the incidence of hypoxic–ischemic insult in preterm infants is probably higher than recognized and follows a more complex clinical course, with higher rates of adverse neurological outcomes, compared to term infants. This review aims to elucidate the causes and consequences of preterm hypoxia–ischemia, the subsequent clinical encephalopathy syndrome, diagnostic tools, and outcomes. Finally, we suggest a uniform definition for preterm HIE that may help in identifying infants most at risk of adverse outcomes and amenable to neuroprotective therapies. PMID:27812521

  1. Ischemic ulcers - self-care

    MedlinePlus

    ... that can cause ischemic wounds include: Diseases that cause inflammation, such as lupus High blood pressure High cholesterol levels Chronic kidney disease Blockage of the lymph vessels , which causes fluid ...

  2. Current developments in canine genetics.

    PubMed

    Marschall, Yvonne; Distl, Ottmar

    2010-01-01

    In recent years, canine genetics had made huge progress. In 1999 the first complete karyotype and ideogram of the dog was published. Several linkage and RH maps followed. Using these maps, sets of microsatellite markers for whole genome scans were compiled. In 2003 the sequencing of the DNA of a female Boxer began. Now the second version of the dog genome assembly has been put online, and recently, a microchip SNP array became available. Parallel to these developments, some causal mutations for different traits have been identified. Most of the identified mutations were responsible for monogenic canine hereditary diseases. With the tools available now, it is possible to use the advantages of the population structure of the various dog breeds to unravel complex genetic traits. Furthermore, the dog is a suitable model for the research of a large number of human hereditary diseases and particularly for cancer genetics, heart and neurodegenerative diseases. There are some examples where it was possible to benefit from the knowledge of canine genetics for human research. The search for quantitative trait loci (QTL), the testing of candidate genes and genome-wide association studies can now be performed in dogs. QTL for skeletal size variations and for canine hip dysplasia have been already identified and for these complex traits the responsible genes and their possible interactions can now be identified.

  3. The association between ischemic and jeopardized myocardia and all-cause mortality in patients with peripheral artery disease.

    PubMed

    Hammad, Tarek A; Yousefzai, Rayan; Venkatachalam, Sridhar; Lowry, Ashley; Gornik, Heather L; Jaber, Wael; Bartholomew, John R; Kim, Soo Hyun; Cerqueira, Manuel; Gray, Bruce H; Blackstone, Eugene H; Shishehbor, Mehdi H

    2016-04-01

    Peripheral artery disease (PAD) is associated with increased mortality and concomitant coronary artery disease (CAD). However, it is unclear whether uncovering the presence of functional coronary ischemia by single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) would further help stratifying that excess risk. From January 2000 to 2009, 4294 individuals underwent cardiac stress testing within 180 days of ankle-brachial index (ABI) measurements. Of these, 645 had PAD and SPECT MPI stress testing. Abnormal ABI was defined as ⩽ 0.9 or prior lower extremity arterial revascularization. Myocardial ischemic burden and total jeopardized myocardium were represented by the summed difference score (SDS) and summed stress score (SSS), respectively. Univariate and multivariable Cox proportional hazard analyses were used to study the impact of SDS and SSS on all-cause mortality. Additionally, using a hierarchical approach, we examined the step-wise addition of post-stress test coronary and lower extremity arterial revascularizations as time-varying covariates on outcomes. We found no significant difference in all-cause mortality between patients with ischemic myocardium (SDS > 0) and those without (SDS = 0) (adjusted HR: 0.94, 95% CI: 0.53-1.69; p = 0.84). Similarly, the presence of jeopardized myocardium (SSS > 0) did not have a significant impact on mortality (adjusted HR: 1.16, 95% CI: 0.67-2.00; p = 0.59). Moreover, adjustment for post-testing coronary and lower extremity arterial revascularizations did not affect our results. In conclusion, ischemic and jeopardized myocardia are not predictors of all-cause mortality in PAD; thus, SPECT MPI does not appear to be a useful risk stratification tool in these patients.

  4. Auto-oscillations of skinned myocardium correlating with heartbeat.

    PubMed

    Sasaki, Daisuke; Fujita, Hideaki; Fukuda, Norio; Kurihara, Satoshi; Ishiwata, Shin'ichi

    2005-01-01

    Skinned myocardium (or myofibrils) exhibits auto-oscillations of sarcomere length and developed force called SPOC (SPontaneousOscillatoryContraction) under partial activation conditions. In SPOC, each sarcomere repeats the cycle of slow shortening and rapid lengthening, and the lengthening phase propagates sequentially to the adjacent sarcomeres in waves (SPOC wave). In this study, we analyzed the sarcomeric oscillation in SPOC in skinned myocardium of various animal species (rat, rabbit, dog, pig, and cow) with different heart rates. The period of oscillation, the sarcomere shortening velocity, and the velocity of SPOC wave, strongly correlated with the resting heart rate of the animal species. The shortening velocity in particular was proportional to the resting heart rate. We then examined the motile activity of each cardiac myosin by an in vitro motility assay. The sliding velocity of actin filaments, which is an index of the motile activity of myosin, also correlated with the resting heart rate but the relationship was not proportional. As a result, the ratio of sarcomere shortening velocity in SPOC to the sliding velocity of actin filaments was not constant but became higher with a higher heart rate. This suggests that the sarcomere shortening velocity in SPOC is modulated by some additional factors besides the motile activity of myosin, resulting in the proportional relationship between the shortening velocity of the sarcomere and the resting heart rate.

  5. Structural three-dimensional constitutive law for the passive myocardium.

    PubMed

    Horowitz, A; Lanir, Y; Yin, F C; Perl, M; Sheinman, I; Strumpf, R K

    1988-08-01

    A three-dimensional constitutive law is proposed for the myocardium. Its formulation is based on a structural approach in which the total strain energy of the tissue is the sum of the strain energies of its constituents: the muscle fibers, the collagen fibers and the fluid matrix which embeds them. The ensuing material law expresses the specific structural and mechanical properties of the tissue, namely, the spatial orientation of the comprising fibers, their waviness in the unstressed state and their stress-strain behavior when stretched. Having assumed specific functional forms for the distribution of the fibers spatial orientation and waviness, the results of biaxial mechanical tests serve for the estimation of the material constants appearing in the constitutive equations. A very good fit is obtained between the measured and the calculated stresses, indicating the suitability of the proposed model for describing the mechanical behavior of the passive myocardium. Moreover, the results provide general conclusions concerning the structural basis for the tissue overall mechanical properties, the main of which is that the collagen matrix, though comprising a relatively small fraction of the whole tissue volume, is the dominant component accounting for its stiffness.

  6. The Role of Uncoupling Protein 2 During Myocardial Dysfunction in a Canine Model of Endotoxin Shock.

    PubMed

    Wang, Xiaoting; Liu, Dawei; Chai, Wenzhao; Long, Yun; Su, Longxiang; Yang, Rongli

    2015-03-01

    To explore the role of uncoupling protein 2 (UCP2) during myocardial dysfunction in a canine model of endotoxin shock, 26 mongrel canines were randomly divided into the following four groups: A (control group; n = 6), B2 (shock after 2 h; n = 7), B4 (shock after 4 h; n = 7), and B6 (shock after 6 h; n = 6). Escherichia coli endotoxin was injected into the canines via the central vein, and hemodynamics were monitored. Energy metabolism, UCP2 mRNA and protein expression, and UCP2 localization were analyzed, and the correlation between energy metabolism changes, and UCP2 expression was determined. After the canine endotoxin shock model was successfully established, the expression of UCP2 mRNA and protein was found to increase, with later time points showing significant increases (P < 0.05). Immunofluorescence assays of UCP2 in heart tissue showed that UCP2 was localized in the cytoplasm, and its expression pattern was the same as that found in the mRNA and protein analyses. The energy metabolism results revealed that the ADP levels increased, but the ATP and phosphocreatine (PCr) levels and ATP/ADP and PCr/ATP ratios decreased in the model. In particular, the PCr/ATP ratio was significantly different from that of the control group 6 h after shock (P < 0.05). Furthermore, correlation analysis showed that the UCP2 protein and mRNA levels were negatively correlated with myocardial energy levels. In summary, decreased energy synthesis can occur in the myocardium during endotoxin shock, and UCP2 may play an important role in this process. The negative correlation between UCP2 expression and energy metabolism requires further study, as the results might contribute to the treatment of sepsis with heart failure.

  7. Immunopathological Features of Canine Myocarditis Associated with Leishmania infantum Infection.

    PubMed

    Costagliola, Alessandro; Piegari, Giuseppe; Otrocka-Domagala, Iwona; Ciccarelli, Davide; Iovane, Valentina; Oliva, Gaetano; Russo, Valeria; Rinaldi, Laura; Papparella, Serenella; Paciello, Orlando

    2016-01-01

    Myocarditis associated with infectious diseases may occur in dogs, including those caused by the protozoa Neospora caninum, Trypanosoma cruzi, Babesia canis, and Hepatozoon canis. However, although cardiac disease due to Leishmania infection has also been documented, the immunopathological features of myocarditis have not been reported so far. The aim of this study was to examine the types of cellular infiltrates and expression of MHC classes I and II in myocardial samples obtained at necropsy from 15 dogs with an established intravitam diagnosis of visceral leishmaniasis. Pathological features of myocardium were characterized by hyaline degeneration of cardiomyocytes, necrosis, and infiltration of mononuclear inflammatory cells consisting of lymphocytes and macrophages, sometimes with perivascular pattern; fibrosis was also present in various degrees. Immunophenotyping of inflammatory cells was performed by immunohistochemistry on cryostat sections obtained from the heart of the infected dogs. The predominant leukocyte population was CD8+ with a fewer number of CD4+ cells. Many cardiomyocytes expressed MHC classes I and II on the sarcolemma. Leishmania amastigote forms were not detected within macrophages or any other cell of the examined samples. Our study provided evidence that myocarditis in canine visceral leishmaniasis might be related to immunological alterations associated with Leishmania infection.

  8. Immunopathological Features of Canine Myocarditis Associated with Leishmania infantum Infection

    PubMed Central

    Piegari, Giuseppe; Otrocka-Domagala, Iwona; Ciccarelli, Davide; Iovane, Valentina; Oliva, Gaetano; Russo, Valeria; Rinaldi, Laura; Papparella, Serenella; Paciello, Orlando

    2016-01-01

    Myocarditis associated with infectious diseases may occur in dogs, including those caused by the protozoa Neospora caninum, Trypanosoma cruzi, Babesia canis, and Hepatozoon canis. However, although cardiac disease due to Leishmania infection has also been documented, the immunopathological features of myocarditis have not been reported so far. The aim of this study was to examine the types of cellular infiltrates and expression of MHC classes I and II in myocardial samples obtained at necropsy from 15 dogs with an established intravitam diagnosis of visceral leishmaniasis. Pathological features of myocardium were characterized by hyaline degeneration of cardiomyocytes, necrosis, and infiltration of mononuclear inflammatory cells consisting of lymphocytes and macrophages, sometimes with perivascular pattern; fibrosis was also present in various degrees. Immunophenotyping of inflammatory cells was performed by immunohistochemistry on cryostat sections obtained from the heart of the infected dogs. The predominant leukocyte population was CD8+ with a fewer number of CD4+ cells. Many cardiomyocytes expressed MHC classes I and II on the sarcolemma. Leishmania amastigote forms were not detected within macrophages or any other cell of the examined samples. Our study provided evidence that myocarditis in canine visceral leishmaniasis might be related to immunological alterations associated with Leishmania infection. PMID:27413751

  9. Ontogeny of canine dimorphism in extant hominoids.

    PubMed

    Schwartz, G T; Dean, C

    2001-07-01

    Many behavioral and ecological factors influence the degree of expression of canine dimorphism for different reasons. Regardless of its socioecological importance, we know virtually nothing about the processes responsible for the development of canine dimorphism. Our aim here is to describe the developmental process(es) regulating canine dimorphism in extant hominoids, using histological markers of tooth growth. Teeth preserve a permanent record of their ontogeny in the form of short- and long-period incremental markings in both enamel and dentine. We selected 52 histological sections of sexed hominoid canine teeth from a total sample of 115, from which we calculated the time and rate of cuspal enamel formation and the rate at which ameloblasts differentiate along the future enamel-dentine junction (EDJ) to the end of crown formation. Thus, we were able to reconstruct longitudinal growth curves for height attainment in male and female hominoid canines. Male hominoids consistently take longer to form canine crowns than do females (although not significantly so for our sample of Homo). Male orangutans and gorillas occasionally take up to twice as long as females to complete enamel formation. The mean ranges of female canine crown formation times are similar in Pan, Gorilla, and Pongo. Interspecific differences between female Pan canine crown heights and those of Gorilla and Pongo, which are taller, result from differences in rates of growth. Differences in canine crown heights between male Pan and the taller, more dimorphic male Gorilla and Pongo canines result both from differences in total time taken to form enamel and from faster rates of growth in Gorilla and Pongo. Although modern human canines do not emerge as significantly dimorphic in this study, it is well-known that sexual dimorphism in canine crown height exists. Larger samples of sexed modern human canines are therefore needed to identify clearly what underlies this.

  10. Global Intracoronary Infusion of Allogeneic Cardiosphere-Derived Cells Improves Ventricular Function and Stimulates Endogenous Myocyte Regeneration throughout the Heart in Swine with Hibernating Myocardium

    PubMed Central

    Suzuki, Gen; Weil, Brian R.; Leiker, Merced M.; Ribbeck, Amanda E.; Young, Rebeccah F.; Cimato, Thomas R.; Canty, John M.

    2014-01-01

    Background Cardiosphere-derived cells (CDCs) improve ventricular function and reduce fibrotic volume when administered via an infarct-related artery using the “stop-flow” technique. Unfortunately, myocyte loss and dysfunction occur globally in many patients with ischemic and non-ischemic cardiomyopathy, necessitating an approach to distribute CDCs throughout the entire heart. We therefore determined whether global intracoronary infusion of CDCs under continuous flow improves contractile function and stimulates new myocyte formation. Methods and Results Swine with hibernating myocardium from a chronic LAD occlusion were studied 3-months after instrumentation (n = 25). CDCs isolated from myocardial biopsies were infused into each major coronary artery (∼33×106 icCDCs). Global icCDC infusion was safe and while ∼3% of injected CDCs were retained, they did not affect ventricular function or myocyte proliferation in normal animals. In contrast, four-weeks after icCDCs were administered to animals with hibernating myocardium, %LADWT increased from 23±6 to 51±5% (p<0.01). In diseased hearts, myocyte proliferation (phospho-histone-H3) increased in hibernating and remote regions with a concomitant increase in myocyte nuclear density. These effects were accompanied by reductions in myocyte diameter consistent with new myocyte formation. Only rare myocytes arose from sex-mismatched donor CDCs. Conclusions Global icCDC infusion under continuous flow is feasible and improves contractile function, regresses myocyte cellular hypertrophy and increases myocyte proliferation in diseased but not normal hearts. New myocytes arising via differentiation of injected cells are rare, implicating stimulation of endogenous myocyte regeneration as the primary mechanism of repair. PMID:25402428

  11. Use-dependent effects of lidocaine on conduction in canine myocardium: application of the modulated receptor hypothesis in vivo.

    PubMed

    Davis, J; Matsubara, T; Scheinman, M M; Katzung, B; Hondeghem, L H

    1986-07-01

    Lidocaine is a commonly used antiarrhythmic drug that causes use-dependent blockade of sodium channels in vitro and reduces conduction velocity in vitro and in vivo. According to the modulated receptor hypothesis of antiarrhythmic drug action, lidocaine has a low affinity for rested sodium channels but a high affinity for open and inactivated channels. In the present experiments, we characterized use-dependent conduction slowing and recovery from slowing by lidocaine in anesthetized dogs. The His-to-ventricular conduction interval was used as the indicator of conduction velocity. We found that prolongation of conduction time was greater as the stimulation frequency was increased. Moreover, on abruptly changing the stimulation frequency, a new steady-state conduction time was approached in two to three depolarizations. On discontinuation of stimulation, the conduction time of progressively less premature extrastimuli shortened exponentially with a terminal phase time constant of 152 +/- 115 msec. These effects by lidocaine were enhanced during acidosis and enhancement was reversed by correction of the acidosis. It is concluded that the effects in vivo of lidocaine on conduction under several conditions of rate, rhythm, and pH are similar to its effects on the maximum upstroke velocity of the action potential in vitro. Although these experiments were not designed to validate the modulated receptor hypothesis, it appears that the modulated receptor hypothesis can predict the effects of lidocaine on conduction in vivo.

  12. Novel diabetes mellitus treatment: mature canine insulin production by canine striated muscle through gene therapy.

    PubMed

    Niessen, S J M; Fernandez-Fuente, M; Mahmoud, A; Campbell, S C; Aldibbiat, A; Huggins, C; Brown, A E; Holder, A; Piercy, R J; Catchpole, B; Shaw, J A M; Church, D B

    2012-07-01

    Muscle-targeted gene therapy using insulin genes has the potential to provide an inexpensive, low maintenance alternative or adjunctive treatment method for canine diabetes mellitus. A canine skeletal muscle cell line was established through primary culture, as well as through transdifferentiation of canine fibroblasts after infection with a myo-differentiation gene containing adenovirus vector. A novel mutant furin-cleavable canine preproinsulin gene insert (cppI4) was designed and created through de novo gene synthesis. Various cell lines, including the generated canine muscle cell line, were transfected with nonviral plasmids containing cppI4. Insulin and desmin immunostaining were used to prove insulin production by muscle cells and specific canine insulin ELISA to prove mature insulin secretion into the medium. The canine myoblast cultures proved positive on desmin immunostaining. All cells tolerated transfection with cppI4-containing plasmid, and double immunostaining for insulin and desmin proved present in the canine cells. Canine insulin ELISA assessment of medium of cppI4-transfected murine myoblasts and canine myoblast and fibroblast mixture proved presence of mature fully processed canine insulin, 24 and 48 h after transfection. The present study provides proof of principle that canine muscle cells can be induced to produce and secrete canine insulin on transfection with nonviral plasmid DNA containing a novel mutant canine preproinsulin gene that produces furin-cleavable canine preproinsulin. This technology could be developed to provide an alternative canine diabetes mellitus treatment option or to provide a constant source for background insulin, as well as C-peptide, alongside current treatment options.

  13. Observations on the effects of CO2-laser on rat myocardium.

    PubMed

    Owen, E R; Canfield, P; Bryant, K; Hopwood, P R

    1984-01-01

    The effect of CO2-laser burn on rat myocardium was studied to evaluate a hypothesis developed by Mirhoseini and Cayton that infarcted myocardium may be revascularized by establishing an alternative circulation from a ventricle to the coronary arteries by means of laser channels burned through the myocardium. The hearts of 22 rats were examined histologically for a period ranging from a few minutes to 50 days after CO2 laser was applied to the myocardium. The laser initiated an intense inflammatory response in the myocardium adjacent to the target site. The authors believe that the inflammatory response, observed in this study to the Biophy-Las 80 surgical laser, must be reduced if laser is to be an effective means of myocardial revascularization.

  14. Asymmetrical distribution of ion channels in canine and human left-ventricular wall: epicardium versus midmyocardium.

    PubMed

    Szabó, Gergely; Szentandrássy, Norbert; Bíró, Tamás; Tóth, Balázs I; Czifra, Gabriella; Magyar, János; Bányász, Tamás; Varró, András; Kovács, László; Nánási, Péter P

    2005-08-01

    The aim of the present study was to compare the distribution of ion currents and the major underlying ion channel proteins in canine and human subepicardial (EPI) and midmyocardial (MID) left-ventricular muscle. Ion currents and action potentials were recorded from canine cardiomyocytes derived from the very superficial EPI and central MID regions of the left ventricle. Amplitude, duration and the maximum velocity of depolarization of the action potential were significantly greater in MID than EPI myocytes, whereas phase-1 repolarization was more pronounced in the EPI cells. Amplitudes of the transient outwards K+ current (29.5+/-1.5 vs. 19.0+/-2.3 pA/pF at +50 mV) and the slow component of the delayed rectifier K+ current (10.3+/-2.3 vs. 6.5+/-1.0 pA/pF at +50 mV) were significantly larger in EPI than in MID myocytes under whole-cell voltage-clamp conditions. The densities of the inwards rectifier K+ current, rapid delayed rectifier K+ current and L-type Ca2+ current were similar in both cell types. Expression of channel proteins in both canine and human ventricular myocardium was determined by Western blotting. In the canine heart, the expression of Kv4.3, Kv1.4, KChIP2 and KvLQT1 was significantly higher, and that of Nav1.5 and MinK much lower, in EPI than in MID. No significant EPI-MID differences were observed in the expression of the other channel proteins studied (Kir2.1, alpha1C, HERG and MiRP1). Similar results were obtained in human hearts, although the HERG was more abundant in the EPI than in the MID layer. In the canine heart, the EPI-MID differences in ion current densities were proportional to differences in channel protein expression. Except for the density of HERG, the pattern of EPI-MID distribution of ion-channel proteins was identical in canine and human ventricles.

  15. Cytokine mRNA expression in postischemic/reperfused myocardium.

    PubMed Central

    Herskowitz, A.; Choi, S.; Ansari, A. A.; Wesselingh, S.

    1995-01-01

    While the role of cytokines in mediating injury during hind limb skeletal muscle ischemia followed by reperfusion has recently been described, the role of cytokines in myocardial infarction and ischemia/reperfusion have remained relatively unexplored. We hypothesize that cytokines play an important role in the regulation of postischemic myocardial inflammation. This study reports the temporal sequence of proinflammatory cytokine gene expression in postischemic/reperfused myocardium and localizes interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha)-protein by immunostaining. Rats were subjected to either permanent left anterior descending (LAD) occlusion or to 35 minutes of LAD occlusion followed by reperfusion and sacrificed up to 7 days later. Rat-specific oligonucleotide probes were used to semiquantitatively assess the relative expression of mRNA for TNF-alpha, IL-1 beta, IL-2, IL-6, interferon-gamma (IFN-gamma), and transforming growth factor-beta 1 (TGF-beta 1) utilizing the reverse transcriptase-polymerase chain reaction amplification technique. Increased cardiac mRNA levels for all cytokines except IL-6 and IFN-gamma were measurable within 15 to 30 minutes of LAD occlusion and increased levels were generally sustained for 3 hours. During early reperfusion, mRNA levels for IL-6 and TGF-beta 1 were significantly reduced compared with permanent LAD occlusion. In both groups, cytokine mRNA levels all returned to baseline levels at 24 hours, while IL-1 beta, TNF-alpha, and TGF-beta 1 mRNA levels again rose significantly at 7 days only in animals with permanent LAD occlusion. Immunostaining for IL-1 beta and TNF-alpha protein revealed two patterns of reactivity: 1) microvascular staining for both IL-1 beta and TNF-alpha protein only in postischemic reperfused myocardium in early post-reperfusion time points; and 2) staining of infiltrating macrophages in healing infarct zones which was most prominent at 7 days after permanent LAD occlusion

  16. Persistent induction of HIF-1alpha and -2alpha in cardiomyocytes and stromal cells of ischemic myocardium.

    PubMed

    Jürgensen, Jan Steffen; Rosenberger, Christian; Wiesener, Michael S; Warnecke, Christina; Hörstrup, Jan H; Gräfe, Michael; Philipp, Sebastian; Griethe, Wanja; Maxwell, Patrick H; Frei, Ulrich; Bachmann, Sebastian; Willenbrock, Roland; Eckardt, Kai-Uwe

    2004-09-01

    Hypoxia-inducible factor (HIF)-1alpha and -2alpha are key regulators of the transcriptional response to hypoxia and pivotal in mediating the consequences of many disease states. In the present work, we define their temporo-spatial accumulation after myocardial infarction and systemic hypoxia. Rats were exposed to hypoxia or underwent coronary artery ligation. Immunohistochemistry was used for detection of HIF-1alpha and -2alpha proteins and target genes, and mRNA levels were determined by RNase protection. Marked nuclear accumulation of HIF-1alpha and -2alpha occurred after both systemic hypoxia and coronary ligation in cardiomyocytes as well as interstitial and endothelial cells (EC) without pronounced changes in HIF mRNA levels. While systemic hypoxia led to widespread induction of HIF, expression after coronary occlusion occurred primarily at the border of infarcted tissue. This expression persisted for 4 wk, included infiltrating macrophages, and colocalized with target gene expression. Subsets of cells simultaneously expressed both HIF-alpha subunits, but EC more frequently induced HIF-2alpha. A progressive increase of HIF-2alpha but not HIF-1alpha occurred in areas remote from the infarct, including the interventricular septum. Cardiomyocytes and cardiac stromal cells exhibit a marked potential for a prolonged transcriptional response to ischemia mediated by HIF. The induction of HIF-1alpha and -2alpha appears to be complementary rather than solely redundant.

  17. Geranylgeranylacetone attenuates myocardium ischemic/reperfusion injury through HSP70 and Akt/GSK-3β/eNOS pathway

    PubMed Central

    Zhou, Chunxia; Bai, Jie; Jiang, Chuan; Ye, Lincai; Pan, Yanjun; Zhang, Haibo

    2017-01-01

    Early reperfusion of myocardial infarction area is the most effective and important therapy to acute myocardial infarction, but could induce reperfusion injury. Geranylgeranylacetone (GGA), an acyclic polyisoprenoid used as an oral anti-ulcer medication, has been reported to have protective effects on reperfusion injury. In the present study, we explored the protective effect of GGA against MIRI and the underlying mechanism. We pretreated rats with four daily GGA, and then observed its effects on heart function parameters following in situ ischemia/reperfusion. GGA exhibited dramatic improvement in cardiac functions, as manifested by increased LVSP and ± (dP/dt) max and decreased LVDP. Oxidative injury and inflammatory response were also relieved by GGA. Western blot showed that the HSP70 protein expression and the Akt/GSK-3β/eNOS pathway were activated. The inhibition of HSP70 and the Akt/GSK-3β/eNOS pathway significantly reversed the protective effects of GGA on MIRI, indicating the involvements of HSP70 and the Akt/GSK-3β/eNOS pathway. PMID:28337268

  18. Qi-Shen-Yi-Qi Dripping Pills Promote Angiogenesis of Ischemic Cardiac Microvascular Endothelial Cells by Regulating MicroRNA-223-3p Expression

    PubMed Central

    Dai, Guo-Hua; Liu, Ning; Zhu, Jing-Wei; Yao, Jing; Yang, Chun; Ma, Pei-Ze; Song, Xian-Bo

    2016-01-01

    Traditional Chinese medicine (TCM) research shows that Qi-Shen-Yi-Qi Dripping Pills (QSYQ) can promote ischemic cardiac angiogenesis. Studies have shown that microRNAs (miRNAs) are the key component of gene regulation networks, which play a vital role in angiogenesis and cardiovascular disease. Mechanisms involving miRNA by which TCM promotes ischemic cardiac angiogenesis have not been reported. We found that microRNA-223-3p (mir-223-3p) was the core miRNA of angiogenesis of rats ischemic cardiac microvascular endothelial cells (CMECs) and inhibited angiogenesis by affecting RPS6KB1/HIF-1α signal pathway in previous study. Based on the results, we observed biological characteristics and optimal dosage for QSYQ intervening in rats ischemic CMECs angiogenesis and concluded that QSYQ low-dose group had the strongest ability to promote angiogenesis of ischemic myocardium. Using miRNA chip and real-time PCR techniques in this study, we identified mir-223-3p as the pivotal miRNA in QSYQ that regulated angiogenesis of ischemic CMECs. From real-time PCR and western blot analysis, research showed that gene and protein expression of factors located RPS6KB1/HIF-1α signaling pathway, including HIF-1α, VEGF, MAPK, PI3K, and AKT, were significantly upregulated by QSYQ to regulate angiogenesis of ischemic CMECs. This study showed that QSYQ promote ischemic cardiac angiogenesis by downregulating mir-223-3p expression in rats ischemic CMECs. PMID:27057198

  19. Rewarming Rate of the Myocardium During the Aortic Cross-Clamp Time: Variations with Different Levels of Body Hypothermia

    PubMed Central

    Juffé, Alberto; Burgos, Raul; Montero, Carlos Garcia; Tellez, Gaberiel; Prades, Gonzalo; Lloves, Eduardo; Figuera, Diego

    1985-01-01

    Twenty patients underwent elective cardiac valve replacement at 20° C of body hypothermia. Temperatures of the ventricles of both walls were monitored on 12 different sites. Distribution of myocardial temperature ranged between 24.3 and 29.3° C for patients of Group I before cardioplegia delivery and 13.2° C in the septum after cardioplegic infusion. Average temperatures for the anterior and posterior wall were 13.6 C and 15° C in the left ventricle and 14.7 and 15° C in the right ventricle. Myocardial temperatures ranged from 26 to 28.7° C for patients of Group II. After cardioplegic arrest, septal temperatures averaged 14.9° C. The recorded sites of the anterior and posterior left ventricle were 14.1 and 13.1° C. The effects of rewarming on the different myocardial areas occurred according to a logarithmic equation, which is faster in the first 10 minutes. The data suggest that the myocardium can be adequately protected with 25° C hypothermia when the cross-clamp period is shorter than 60 minutes. When longer ischemic periods are expected, myocardial protection is best accomplished with 20° C hypothermia. PMID:15227003

  20. Increased uptake of 18F-fluorodeoxyglucose in postischemic myocardium of patients with exercise-induced angina

    SciTech Connect

    Camici, P.; Araujo, L.I.; Spinks, T.; Lammertsma, A.A.; Kaski, J.C.; Shea, M.J.; Selwyn, A.P.; Jones, T.; Maseri, A.

    1986-07-01

    Regional myocardial perfusion and exogenous glucose uptake were assessed with rubidium-82 (82Rb) and 18F-2-fluoro-2-deoxyglucose (FDG) in 10 normal volunteers and 12 patients with coronary artery disease and stable angina pectoris by means of positron emission tomography. In patients at rest, the myocardial uptake of /sup 82/Rb and FDG did not differ significantly from that measured in normal subjects. The exercise test performed within the positron camera in eight patients produced typical chest pain and ischemic electrocardiographic changes in all. In each of the eight patients a region of reduced cation uptake was demonstrated in the /sup 82/Rb scan recorded at peak exercise, after which uptake of /sup 82/Rb returned to the control value 5 to 14 min after the end of the exercise. In these patients, FDG was injected in the recovery phase when all the variables that were altered during exercise, including regional myocardial /sup 82/Rb uptake, had returned to control values. In all but one patient, FDG accumulation in the regions of reduced /sup 82/Rb uptake during exercise was significantly higher than that in the nonischemic regions, i.e., the ones with a normal increment of /sup 82/Rb uptake on exercise. In the nonischemic areas, FDG uptake was not significantly different from that found in normal subjects after exercise. In conclusion, myocardial glucose transport and phosphorylation seem to be enhanced in the postischemic myocardium of patients with exercise-induced ischemia.

  1. An analysis of the cable properties of frog ventricular myocardium.

    PubMed Central

    Chapman, R A; Fry, C H

    1978-01-01

    1. The passive and active electrical parameters of frog ventricular myocardium have been measured. 2. The cytoplasmic resistivity has been determined by following changes in the resistance of a micro-electrode on penetration of a cell. 3. Unidimensional cable analysis using direct and alternating currents revealed the presence of a single time constant attributed to the surface membrane. 4. Longitudinal impedance measurements indicate that a second time constant is present in the intracellular pathway. 5. The results indicate that the resistance between cells is low so that action potentials can propagate from cell to cell by local circuits. 6. A three-dimensional cable analysis has also been carried out and compared to a simplified mathematical model which is presented in an Appendix and which closely approximates the experimental situation. PMID:309942

  2. [The contractile, regulatory and structural proteins of myocardium].

    PubMed

    Adamcová, Michaela; Pelouch, Václav

    2003-01-01

    The myocardium consists of three basic categories of proteins. The myofibrillar proteins trasform the chemical energy of ATP to the mechanical work of the heart. The metabolic proteins located both in the cytosol and in the mitochondrial compartments provide energy for the cardiac contraction. The interstitial space between myocytes is occupied by the extracellular proteins (collagens, glycoproteins, glycosaminoglycans, elastins). By far the greater percentage of myofibrillar proteins (about 80%) is that concerned with contraction (actin and myosin), with about 10% concerned with its regulation (troponin, tropomyosin and tropomodulin) and another 10% concerned with maintenance of the structure of myofibril (C, M-, H-proteins, myomesin, nebulette, alpha-actinin, titin, CapZ protein). Most collagenous and non-collagenous proteins exist in many isoforms that originate from the same genom but are the product of alternative splicing of a primary RNA transcript.

  3. Partition of xenon and iodoantipyrine among erythrocytes, plasma, and myocardium.

    PubMed

    Carlin, R; Chien, S

    1977-05-01

    A new method was developed for determining directly the distribution of 133Xe between red cells and plasma in vitro without an air-fluid interface; the partitioning of 133Xe and 133-i-iodantipyrine between blood and myocardium was investigated in the dog in situ. The red cell-plasma partition coefficient for 133Xe (lambdacpX, unit: ml/ml) at 37 degrees C was 2.27 +/- 0.07 (mean +/- SD) for human blood and 3.31 +/- 0.06 for dog blood. The red cell-plasma partition coefficient for 131I-iodantipyrine (lambdacpI, ml/ml) was 0.75 +/- 0.04 for human blood and 0.97 +/- 0.03 for dog blood. lambdacpX and lambdacpI did not change significantly after the intravenous administration of sodium pentobarbital (30 mg/kg) into the dog. lambdacpX of dog blood varied inversely with temperature, whereas lambdacpI showed very little change with temperature. The blood-left ventricle partition coefficient for 133Xe (lambda'btX, corrected for trapped blood) varied directly with directly with red cell volume fraction (H): lambda'btX = 1.32 + 2.00 H. Blood-left ventricle partition coefficient for 131I-iodoanitpyrine did not vary significantly with H. The results support the concept of a three-compartment partition of the indicator among erythrocytes, plasma, and myocardium. The mean values (+/- SD) of the hematocrit-independent plasma-tissue partition coefficient in the left ventricle for 133Xe and 131I-iodoantipyrine were 1.08 +/- 0.16 and 1.54 +/- 0.20 g/ml, respectively.

  4. Growth differentiation factor 15 may protect the myocardium from no‑reflow by inhibiting the inflammatory‑like response that predominantly involves neutrophil infiltration.

    PubMed

    Zhang, Mei; Pan, Kunying; Liu, Qianping; Zhou, Xin; Jiang, Tiemin; Li, Yuming

    2016-01-01

    The aim of the current study was to investigate the time course of the expression of growth differentiation factor‑15 (GDF‑15) in rat ischemic myocardium with increasing durations of reperfusion, and to elucidate its physiopathological role in the no‑reflow phenomenon. Wistar rats were randomly divided into ischemia reperfusion (I/R) and sham groups, and myocardial I/R was established by ligation of the left anterior descending coronary artery for 1 h followed by reperfusion for 2, 4, 6, 12, 24 h and 7 days whilst rats in the sham group were subjected to a sham operation. The expression levels of GDF‑15 and ICAM‑1 were measured, in addition to myeloperoxidase (MPO) activity. The myocardial anatomical no‑reflow and infarction areas were assessed. The area at risk was not significantly different following various periods of reperfusion, while the infarct area and no‑reflow area were significantly greater following 6 h of reperfusion (P<0.05). The mRNA and protein expression levels of GDF‑15 were increased during the onset and development of no‑reflow, and peaked following 24 h of reperfusion. MPO activity was reduced with increasing reperfusion duration, while ICAM‑1 levels were increased. Hematoxylin and eosin staining demonstrated that myocardial neutrophil infiltration was significantly increased by I/R injury, in particular following 2, 4 and 6 h of reperfusion. GDF‑15 expression levels were negatively correlated with MPO activity (r=‑0.55, P<0.001), and the MPO activity was negatively correlated with the area of no‑reflow (r=‑0.46, P<0.01). By contrast, GDF‑15 was significantly positively correlated with ICAM‑1 levels (r=0.52, P<0.01), which additionally were demonstrated to be significantly positively associated with the size of the no‑reflow area (r=0.39, P<0.05). The current study demonstrated the time course effect of reperfusion on the expression of GDF‑15 in the myocardial I/R rat model, with the shorter reperfusion

  5. Growth differentiation factor 15 may protect the myocardium from no-reflow by inhibiting the inflammatory-like response that predominantly involves neutrophil infiltration

    PubMed Central

    ZHANG, MEI; PAN, KUNYING; LIU, QIANPING; ZHOU, XIN; JIANG, TIEMIN; LI, YUMING

    2016-01-01

    The aim of the current study was to investigate the time course of the expression of growth differentiation factor-15 (GDF-15) in rat ischemic myocardium with increasing durations of reperfusion, and to elucidate its physiopathological role in the no-reflow phenomenon. Wistar rats were randomly divided into ischemia reperfusion (I/R) and sham groups, and myocardial I/R was established by ligation of the left anterior descending coronary artery for 1 h followed by reperfusion for 2, 4, 6, 12, 24 h and 7 days whilst rats in the sham group were subjected to a sham operation. The expression levels of GDF-15 and ICAM-1 were measured, in addition to myeloperoxidase (MPO) activity. The myocardial anatomical no-reflow and infarction areas were assessed. The area at risk was not significantly different following various periods of reperfusion, while the infarct area and no-reflow area were significantly greater following 6 h of reperfusion (P<0.05). The mRNA and protein expression levels of GDF-15 were increased during the onset and development of no-reflow, and peaked following 24 h of reperfusion. MPO activity was reduced with increasing reperfusion duration, while ICAM-1 levels were increased. Hematoxylin and eosin staining demonstrated that myocardial neutrophil infiltration was significantly increased by I/R injury, in particular following 2, 4 and 6 h of reperfusion. GDF-15 expression levels were negatively correlated with MPO activity (r=−0.55, P<0.001), and the MPO activity was negatively correlated with the area of no-reflow (r=−0.46, P<0.01). By contrast, GDF-15 was significantly positively correlated with ICAM-1 levels (r=0.52, P<0.01), which additionally were demonstrated to be significantly positively associated with the size of the no-reflow area (r= 0.39, P<0.05). The current study demonstrated the time course effect of reperfusion on the expression of GDF-15 in the myocardial I/R rat model, with the shorter reperfusion times (6 h) resulting in

  6. Effects Of Continuous Argon Laser Irradiation On Canine And Autopsied Human Cardiac Tissue

    NASA Astrophysics Data System (ADS)

    Ben-Shachar, Giora; Sivakoff, Mark; Bernard, Steven L.; Dahms, Beverly B.; Riemenschneider, Thomas A.

    1984-10-01

    In eight human formalin preserved cardiac specimens, various cardiac and vascular obstructions were relieved by argon laser irradiation. Interatrial communication was also produced by a transar'rial approach in a live dog. In-vivo fresh canine cardiac tissues required power density of at feast 80, 90, and 110 watts/cm2 for vaporization of myocardial, vascular and valvular tissues respectively. The fiber tip to tissue distance (effective irradiation distance) for effective vaporization was less than I mm for vascular and valvular tissues and less than 4 mm for myocardium. Light microscopy showed four zones of histological damage common to all tissues - central crater surrounded by layers of charring, vacuolization and coagulation necorsis. Myocardium showed additionally a layer of normal appearing muscle cells (skip area) surrounded by a peripheral coagulation halo. Laser irradiation effects on valvular tissue showed the most lateral extension of coagulation necrosis. It is concluded that palliation and treatment of certain congenital heart defects by laser irradiation is anatomi-cally feasible and may be safe for in vivo application when low power output and short exposure time are used from a very short irradiation distance.

  7. Quantification of fiber orientation in the canine atrial pacemaker complex using optical coherence tomography

    PubMed Central

    Ambrosi, Christina M.; Fedorov, Vadim V.; Schuessler, Richard B.; Rollins, Andrew M.

    2012-01-01

    Abstract The atrial pacemaker complex is responsible for the initiation and early propagation of cardiac impulses. Optical coherence tomography (OCT), a nondestructive imaging modality with spatial resolutions of ∼1 to 15 μm, can be used to identify unique fiber orientation patterns in this region of the heart. Functionally characterized canine sinoatrial nodes (SAN) (n=7) were imaged using OCT up to ∼1  mm below the endocardial tissue surface. OCT images were directly compared to their corresponding histological sections. Fiber orientation patterns unique to the crista terminalis (CT), SAN, and surrounding atrial myocardium were identified with dominant average fiber angles of 89±12  deg, 110±16  deg, and 95±35  deg, respectively. Both the CT and surrounding atrial myocardium displayed predominantly unidirectionally based fiber orientation patterns within each specimen, whereas the SAN displayed an increased amount of fiber disarray manifested quantitatively as a significantly greater standard deviation in fiber angle distribution within specimens [33±7  deg versus 23±5  deg, atrium (p=0.02); 18±3  deg, CT (p=0.0003)]. We also identified unique, local patterns of fiber orientation specific to the functionally characterized block zone. We demonstrate the ability of OCT in detecting components of the atrial pacemaker complex which are intimately involved in both normal and abnormal cardiac conduction. PMID:22894470

  8. Canine histiocytic neoplasia: An overview

    PubMed Central

    Fulmer, Amanda K.; Mauldin, Glenna E.

    2007-01-01

    Canine histiocytic neoplasms include cutaneous histiocytoma, as well as localized and disseminated histiocytic sarcoma. These tumors have variable biologic behavior, although the malignant disorders often have a poor prognosis. Immunohistochemistry plays an essential role in differentiating histiocytic tumors from other neoplasias that may have similar histological appearances. This allows a definitive diagnosis to be established and provides a more accurate prediction of prognosis. This article reviews the biologic behavior, diagnosis, and treatment of histiocytic tumors in the dog. PMID:17987966

  9. Sewage surveillance reveals the presence of canine GVII norovirus and canine astrovirus in Uruguay.

    PubMed

    Lizasoain, A; Tort, L F L; García, M; Gómez, M M; Leite, J P G; Miagostovich, M P; Cristina, J; Berois, M; Colina, R; Victoria, Matías

    2015-11-01

    Canine norovirus (NoV) and astrovirus (AstV) were studied in 20 domestic sewage samples collected in two cities in Uruguay. Four samples were characterized as canine AstV after phylogenetic analysis clustering with strains detected in Italy and Brazil in 2008 and 2012, respectively. One sample was characterized as canine NoV and clustered with a strain detected in Hong Kong and recently classified as GVII. This study shows the occurrence of a canine NoV GVII strain for the first time in the American continent and also warns about possible zoonotic infection, since canine strains were detected in domestic sewage.

  10. Quantitation of the critically ischemic zone at risk during acute coronary occlusion using PET

    SciTech Connect

    Merhige, M.; Garza, D.; Sease, D.; Rowe, R.W.; Tewson, T.; Emran, A.; Bolomey, L.; Gould, K.L. )

    1991-08-01

    Critical myocardial ischemia has been defined experimentally during acute coronary occlusion as flow reduction of 50% or more since cellular ATP depletion begins to occur beyond this flow reduction threshold, placing tissue at risk of cellular injury. To test the hypothesis that critically ischemic fractional left ventricular mass can be measured noninvasively with PET, nine dogs were imaged in a multi-slice positron camera using the perfusion tracer 13N-ammonia, while radiolabeled microspheres were injected into the left atrium during acute coronary occlusion. Images were processed using a 50% threshold and the size of the resulting perfusion defect was expressed as a fraction of total left ventricular image volume. The critically ischemic left ventricular fraction determined in vitro from the microsphere perfusion data, ranged from 5% to 30% of the total left ventricular weight and correlated closely with that determined noninvasively by PET with r = 0.94 (y = 1.05X - 2.0%). The authors conclude that the fraction of left ventricular myocardium rendered critically ischemic during acute coronary occlusion can be measured accurately and noninvasively in vivo using perfusion imaging with positron emission tomography.

  11. Remote ischemic preconditioning for prevention of high-altitude diseases: fact or fiction?

    PubMed

    Berger, Marc Moritz; Macholz, Franziska; Mairbäurl, Heimo; Bärtsch, Peter

    2015-11-15

    Preconditioning refers to exposure to brief episodes of potentially adverse stimuli and protects against injury during subsequent exposures. This was first described in the heart, where episodes of ischemia/reperfusion render the myocardium resistant to subsequent ischemic injury, which is likely caused by reactive oxygen species (ROS) and proinflammatory processes. Protection of the heart was also found when preconditioning was performed in an organ different from the target, which is called remote ischemic preconditioning (RIPC). The mechanisms causing protection seem to include stimulation of nitric oxide (NO) synthase, increase in antioxidant enzymes, and downregulation of proinflammatory cytokines. These pathways are also thought to play a role in high-altitude diseases: high-altitude pulmonary edema (HAPE) is associated with decreased bioavailability of NO and increased generation of ROS, whereas mechanisms causing acute mountain sickness (AMS) and high-altitude cerebral edema (HACE) seem to involve cytotoxic effects by ROS and inflammation. Based on these apparent similarities between ischemic damage and AMS, HACE, and HAPE, it is reasonable to assume that RIPC might be protective and improve altitude tolerance. In studies addressing high-altitude/hypoxia tolerance, RIPC has been shown to decrease pulmonary arterial systolic pressure in normobaric hypoxia (13% O2) and at high altitude (4,342 m). Our own results indicate that RIPC transiently decreases the severity of AMS at 12% O2. Thus preliminary studies show some benefit, but clearly, further experiments to establish the efficacy and potential mechanism of RIPC are needed.

  12. Canine adenovirus based rabies vaccines.

    PubMed

    Tordo, N; Foumier, A; Jallet, C; Szelechowski, M; Klonjkowski, B; Eloit, M

    2008-01-01

    Adenovirus based vectors are very attractive candidates for vaccination purposes as they induce in mammalian hosts potent humoral, mucosal and cellular immune responses to antigens encoded by the inserted genes. We have generated E1-deleted and replication-competent recombinant canine type-2 adenoviruses expressing the rabies virus glycoprotein (G). The effectiveness of both vectors to express a native G protein has been characterized in vitro in permissive cell lines. We compared the humoral and cellular immune responses induced in mice by intramuscular injection of the recombinant canine adenovirus vectors with those induced by a human (Ad5) E1-deleted virus expressing the same rabies G protein. Humoral responses specific to the adenoviruses or the rabies glycoprotein antigens were studied. The influence of the mouse strain was observed using replication-competent canine adenovirus. A high level of rabies neutralizing antibody was observed upon i.m. inoculation, and 100% of mice survived lethal challenge. These results are very promising in the perspective of oral vaccine for dog rabies control.

  13. Characterization of canine neutrophil granules.

    PubMed Central

    O'Donnell, R T; Andersen, B R

    1982-01-01

    The purpose of this study was to isolate distinct populations of canine neutrophil granules and to compare them with neutrophil granules from other species. Size, shape, density, and content of canine neutrophil granules were determined. Neutrophils obtained by Ficoll-Hypaque sedimentation were homogenized, and granule populations were separated by isopycnic centrifugation on a linear sucrose gradient (rho, 1.14 to 1.22 g/ml). The most dense granule population (rho, 1.197 g/ml) contained all of the myeloperoxidase, beta-glucuronidase, and elastase, more than half of the acid beta-glycerophosphatase, and most of the lysozyme. The population with intermediate density (rho, 1.179 g/ml) contained lactoferrin, vitamin B12-binding protein, and the remainder of the acid beta-glycerophosphatase and lysozyme. The least dense granule population did not contain a major peak of any of the enzymes or binding proteins tested but was distinguished by density and morphology. The size and shape of the granules were determined from scanning electron micrographs and assessment of shape was aided by transmission electron micrographs. By these methods three populations of canine neutrophil granules were characterized and named: myeloperoxidase granules, vitamin B12-binding protein granules, and low-density granules. Images PMID:6292095

  14. HYPERTENSIVE-ISCHEMIC LEG ULCERS

    PubMed Central

    Farber, Eugene M.; Schmidt, Otto E. L.

    1950-01-01

    Ischemic ulcers of the leg having characteristics different from those of ordinary leg ulcers have been observed in a small number of hypertensive patients, mostly women, during the past few years. Such ulcers are usually located above the ankle. They begin with a small area of purplish discoloration at the site of slight trauma, and progress to acutely tender ulceration. In studies of tissue removed from the margin and the base of an ulcer of this kind, obliterative arteriolar sclerotic changes, ischemic-appearing connective tissue and inflammatory changes were noted. Two additional cases are reported. ImagesFigure 1.Figure 2.Figure 3.Figure 4. PMID:15398887

  15. [Antioxidant therapy in ischemic stroke].

    PubMed

    Suslina, Z A; Federova, T N; Maksimova, M Iu; Riasina, T V; Stvolinskiĭ, S L; Khrapova, E V; Boldyrev, A A

    2000-01-01

    The paper presents the results of investigation of emoxipin, an antioxidant synthetic drug, for treatment of patients with ischemic disorders of cerebral circulation. The drug produced a beneficial clinical effect in patients with lacunar and cardioembolic strokes of moderate severity. Therapy with emoxipin increased endogenic antioxidant activity and improved a clinical status of the patients. The protective effect of carnosine was demonstrated in experimental acute hypobaric hypoxia and cerebral ischemia in rats. The results obtained permit to recommend an inclusion of both emoxipin and carnosine in a combined treatment of ischemic disorders of cerebral circulation.

  16. The alteration of interelemental ratios in myocardium under the congenital heart disease (SRXRF)

    NASA Astrophysics Data System (ADS)

    Trunova, V. A.; Zvereva, V. V.; Okuneva, G. N.; Levicheva, E. N.

    2007-05-01

    It is the myocardium that bears the basic functional loading during heart working, including muscle contractility and enzyme activity. The elemental concentrations in myocardium tissue of heart were determined by SRXRF technique. Our investigation is systematical: the elemental content in each compartment (left and right ventricles, left and right auricles) of hearts of healthy and diseased children (congenital heart diseases, transposition of main vessels (TMV)) was analyzed. The elemental distribution in myocardium of four heart chambers of human fetuses was also analyzed. Following elements were determined: S, Cl, K, Ca, Cr, Mn, Fe, Ni, Cu, Zn, As, Se, Br, Rb, Sr. It was revealed that the elemental concentrations in myocardium of both ventricles are almost constant in heart of fetuses and healthy children. The transition from pre-natal study (fetus) to post-natal study is accompanied by the redistribution of chemical elements in myocardium. The higher concentrations of S, Fe, Ca, Sr and Cu in myocardium of children are observed, the content of K, Br, Rb and especially Se is lower than in heart of fetuses. The elemental distribution in myocardium of children TMV is considerably different in comparison with the healthy children: the higher levels of Cu are observed. The content of Se is lower.

  17. [Four-week simulated weightlessness increases the expression of atrial natriuretic peptide in the myocardium].

    PubMed

    Zhang, Wen-Cheng; Lu, Yuan-Ming; Yang, Huai-Zhang; Xu, Peng-Tao; Chang, Hui; Yu, Zhi-Bin

    2013-04-25

    One of the major circulatory changes that occur in human during space flight and simulated weightlessness is a cerebral redistribution of body fluids, which is accompanied by an increase of blood volume in the upper body. Therefore, atrial myocardium should increase the secretion of atrial natriuretic peptide (ANP), but the researches lack common conclusion until now. The present study was to investigate the expression level of ANP in simulated weightlessness rats, and to confirm the changes of ANP by observing the associated proteins of soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs). The tail-suspended rat model was used to simulate weightlessness. Western blots were carried out to examine the expression levels of ANP and SNARE proteins in atrial and left ventricular myocardium. The results showed that ANP expression in atrial myocardium showed an increase in 4-week tail-suspended rats (SUS) compared with that in the synchronous control rats (CON). We only detected a trace amount of ANP in the left ventricular myocardium of the CON, but found an enhanced expression of ANP in left ventricular myocardium of the SUS. Expression of VAMP-1/2 (vesicle associated SNARE) increased significantly in both atrial and left ventricular myocardium in the SUS compared with that in the CON. There was no difference of the expression of syntaxin-4 (target compartment associated SNARE) between the CON and SUS, but the expression of SNAP-23 showed an increase in atrial myocardium of the SUS compared with that in the CON. Synip and Munc-18c as regulators of SNAREs did not show significant difference between the CON and SUS. These results suggest that the expression of ANP shows an increase in atrial and left ventricular myocardium of 4-week tail-suspended rats. Enhanced expression of VAMP-1/2 associated with ANP vesicles confirms the increased expression of ANP in atrial and left ventricular myocardium.

  18. Over-expression of CXCR4 on mesenchymal stem cells augments myoangiogenesis in the infarcted myocardium.

    PubMed

    Zhang, Dongsheng; Fan, Guo-Chang; Zhou, Xiaoyang; Zhao, Tiemin; Pasha, Zeeshan; Xu, Meifeng; Zhu, Yi; Ashraf, Muhammad; Wang, Yigang

    2008-02-01

    Bone marrow mesenchymal stem cells (MSCs) participate in myocardial repair following myocardial infarction. However, their in vivo reparative capability is limited due to lack of their survival in the infarcted myocardium. To overcome this limitation, we genetically engineered male rat MSCs overexpressing CXCR4 in order to maximize the effect of stromal cell-derived factor-1alpha (SDF-1alpha) for cell migration and regeneration. MSCs were isolated from adult male rats and cultured. Adenoviral transduction was carried out to over-express either CXCR4/green fluorescent protein (Ad-CXCR4/GFP) or Ad-null/GFP alone (control). Flow cytometry was used to identify and isolate GFP/CXCR4 over-expressing MSCs for transplantation. Female rats were assigned to one of four groups (n=8 each) to receive GFP-transduced male MSCs (2 x 10(6)) via tail vein injection 3 days after ligation of the left anterior descending (LAD) coronary artery: GFP-transduced MSCs (Ad-null/GFP-MSCs, group 1) or MSCs over-expressing CXCR4/GFP (Ad-CXCR4/GFP-MSCs, group 2), or Ad-CXCR4/GFP-MSCs plus SDF-1alpha (50 ng/microl) (Ad-CXCR4/GFP-MSCs/SDF-1alpha, group 3), or Ad-miRNA targeting CXCR4 plus SDF-1alpha (Ad-miRNA/GFP-MSCs+SDF-1alpha treatment, group 4). Cardiodynamic data were obtained 4 weeks after induction of regional myocardial infarction (MI) using echocardiography after which hearts were harvested for immunohistochemical studies. The migration of GFP and Y-chromosome positive cells increased significantly in the peri- and infarct areas of groups 2 and 3 compared to control group (p<0.05), or miRNA-CXCR4 group (p<0.01). The number of CXCR4 positive cells in groups 2, 3 was intimately associated with angiogenesis and myogenesis. MSCs engraftment was blocked by pretreatment with miRNA (group 4). Cardiac function was significantly improved in rats receiving MSCs over-expressing CXCR4 alone or with SDF-1alpha. The up-regulation of matrix metalloproteinases (MMPs) by CXCR4 overexpressing MSCs perhaps

  19. Lasers in the treatment of ischemic heart disease in China

    NASA Astrophysics Data System (ADS)

    Zhang, Yongzhen; Chen, Mingzhe

    2000-10-01

    Myocardial revascularization by laser is a new treatment modality for chronic, severe, refractory angina in the patients with coronary heart disease that is not amenable to angioplasty (PTCA) or bypass surgery (CABG). Transmyocardial revascularization (TMR), typically requiring open thoracotomy, uses laser to create channels that would directly carry blood from left ventricular cavity into the ischemic myocardium. Current data indicate that TMR may provide these patients with improvement in angina severity, quality of life, and myocardial perfusion. The greatest potential future use of TMR is as an adjunct to CABG in patients with disease that prevents bypass grafting due to lack of distal targets or a conduit. Recently, as percutaneous (catheter-based) myocardial revascularization (PMR) has been developed with laser technology that permits the creation of channels from the endocardial surface of the left ventricle. The early results with PMR seem encouraging. Randomized clinical trial has demonstrated symptomatic improvement and increased exercise capacity. The risk: benefit ratio for PMR appears to be much more favorable than that for TMR. The mechanisms of action of them have not yet been clearly elucidated, and several theories have been proposed, including channel patency, angiogenesis, denervation, and placebo effect. The challenge of TMR/PMR is related to improvement of perioperative outcomes and long-term survival without worsening of left ventricular function. In future, it may be feasible to combine TMR/PMR with intramyocardial delivery of angiogenic growth factors to induce further new blood vessel formation.

  20. Early prediction of maxillary canine impaction

    PubMed Central

    Storms, Ann-Sophie; Voet, Martine; Fieuws, Steffen; Willems, Guy

    2016-01-01

    Objectives: The aim of this study was to establish prediction criteria for maxillary canine impaction in young patients, based on angular and linear measurements on panoramic radiographs. Methods: From 828 records having at least 2 panoramic radiographs, both taken between the ages of 7 and 14 years, with a minimum 1-year and maximum 3-year interval (T1 and T2), a training data set consisting of 30 subjects with unilateral canine impaction (12 males and 18 females) was selected. The patients' mean age was 10.1 years [standard deviation (SD) 1.3 years] at T1 and 11.9 years (SD 1.1 years) at T2. The training data set also consisted of 30 maxillary canines from the contralateral sides and an additional 60 normal erupted canines from 30 subjects. Those 30 subjects of a test data set were selected based on displaying bilateral maxillary canine eruption at T2 and being matched for gender and age with the subjects of the training data set [12 males and 18 females; mean age at T1, 10.1 years (SD 1.3 years) and at T2, 11.1 years (SD 1.2 years)]. Angular and linear measurements were performed separately by two observers on the total study sample at T1. Linear measurements were expressed as a multiplication of the maxillary central incisor width at the non-impacted side. Results: Significant differences for linear and angular measurements and radiographic factors were found between the maxillary impacted canine and erupted maxillary canine. The three best-discriminating parameters were canine to first premolar angle, canine cusp to midline distance and canine cusp to maxillary plane distance. These three parameters were combined in a multiple logistic regression model to calculate the probability of impaction, yielding a high area under the curve (AUC) equal to 0.97 (95% confidence interval: 0.94–0.99), with 90% sensitivity and 94% specificity. Conclusions: Prediction of maxillary canine impaction from a combination of parameters relating to angles and distances measured

  1. Molecular signalling pathways in canine gliomas.

    PubMed

    Boudreau, C E; York, D; Higgins, R J; LeCouteur, R A; Dickinson, P J

    2017-03-01

    In this study, we determined the expression of key signalling pathway proteins TP53, MDM2, P21, AKT, PTEN, RB1, P16, MTOR and MAPK in canine gliomas using western blotting. Protein expression was defined in three canine astrocytic glioma cell lines treated with CCNU, temozolamide or CPT-11 and was further evaluated in 22 spontaneous gliomas including high and low grade astrocytomas, high grade oligodendrogliomas and mixed oligoastrocytomas. Response to chemotherapeutic agents and cell survival were similar to that reported in human glioma cell lines. Alterations in expression of key human gliomagenesis pathway proteins were common in canine glioma tumour samples and segregated between oligodendroglial and astrocytic tumour types for some pathways. Both similarities and differences in protein expression were defined for canine gliomas compared to those reported in human tumour counterparts. The findings may inform more defined assessment of specific signalling pathways for targeted therapy of canine gliomas.

  2. Leakage and Water Exchange Characterization of Gadofosveset in the Myocardium

    PubMed Central

    Bane, Octavia; Lee, Daniel C.; Benefield, Brandon C.; Harris, Kathleen R.; Chatterjee, Neil R.; Carr, James C.; Carroll, Timothy J.

    2014-01-01

    Purpose To determine the compartmentalization of the blood pool agent gadofosveset and the effect of its transient binding to albumin on the quantification of steady-state fractional myocardial blood volume (fMBV). Methods Myocardial vascular fraction measurements were simulated assuming the limiting cases (slow or fast) of two-compartment water exchange for different contrast agent injection concentrations, binding fractions, bound and free relaxivities, and true cardiac vascular fractions. fMBV was measured in five healthy volunteers (4 males, 1 female, average age 33) at 1.5 T after administration of five injections of gadofosveset. The measurements in the volunteers were retrospectively compared to measurements of fMBV after three serial injections of the ultra-small, paramagnetic iron oxide (USPIO) blood pool agent ferumoxytol in an experimental animal. The true fMBV and exchange rate of water protons in both human and animal data sets was determined by chi square minimization. Results Simulations showed an error in the measurement of fMBV due to partial binding of gadofosveset of less than 30%. Measured fMBV values over-estimate simulation predictions, and approach cardiac extracellular volume (22%), which suggests that the intravascular assumption may not be appropriate for the myocardium, although it may apply to more distal perfusion beds. In comparison, fMBV measured with ferumoxytol (5%, with slow water proton exchange across vascular wall) agree with published values of myocardial vascular fraction. Further comparison between myocardium relaxation rates induced by gadofosveset and by other extracellular and intravascular contrast agents showed that gadofosveset behaves like an extracellular contrast agent. Conclusions The distribution of the volunteer data indicates that a three-compartment model, with slow water exchange of gadofosveset and water protons between the vascular and interstitial compartments, and fast water exchange between the

  3. Magnetic resonance imaging and multi-detector computed tomography assessment of extracellular compartment in ischemic and non-ischemic myocardial pathologies

    PubMed Central

    Saeed, Maythem; Hetts, Steven W; Jablonowski, Robert; Wilson, Mark W

    2014-01-01

    Myocardial pathologies are major causes of morbidity and mortality worldwide. Early detection of loss of cellular integrity and expansion in extracellular volume (ECV) in myocardium is critical to initiate effective treatment. The three compartments in healthy myocardium are: intravascular (approximately 10% of tissue volume), interstitium (approximately 15%) and intracellular (approximately 75%). Myocardial cells, fibroblasts and vascular endothelial/smooth muscle cells represent intracellular compartment and the main proteins in the interstitium are types I/III collagens. Microscopic studies have shown that expansion of ECV is an important feature of diffuse physiologic fibrosis (e.g., aging and obesity) and pathologic fibrosis [heart failure, aortic valve disease, hypertrophic cardiomyopathy, myocarditis, dilated cardiomyopathy, amyloidosis, congenital heart disease, aortic stenosis, restrictive cardiomyopathy (hypereosinophilic and idiopathic types), arrythmogenic right ventricular dysplasia and hypertension]. This review addresses recent advances in measuring of ECV in ischemic and non-ischemic myocardial pathologies. Magnetic resonance imaging (MRI) has the ability to characterize tissue proton relaxation times (T1, T2, and T2*). Proton relaxation times reflect the physical and chemical environments of water protons in myocardium. Delayed contrast enhanced-MRI (DE-MRI) and multi-detector computed tomography (DE-MDCT) demonstrated hyper-enhanced infarct, hypo-enhanced microvascular obstruction zone and moderately enhanced peri-infarct zone, but are limited for visualizing diffuse fibrosis and patchy microinfarct despite the increase in ECV. ECV can be measured on equilibrium contrast enhanced MRI/MDCT and MRI longitudinal relaxation time mapping. Equilibrium contrast enhanced MRI/MDCT and MRI T1 mapping is currently used, but at a lower scale, as an alternative to invasive sub-endomyocardial biopsies to eliminate the need for anesthesia, coronary

  4. Functional characterization of left ventricular segmental responses during the initial 24 h and 1 wk after experimental canine myocardial infarction.

    PubMed Central

    Roan, P; Scales, F; Saffer, S; Buja, L M; Willerson, J T

    1979-01-01

    Characterization of the temporal evolution of resting segmental function and inotropic reserve after coronary occlusion may be important in evaluating attempts to salvage ischemic but non-necrotic myocardium. Accordingly, we chronically implanted up to six pairs of pulse-transit piezoelectric crystals in the left ventricular myocardium of dogs to measure segmental wall thickness. Segments were separated into groups according to the loss of net systolic thickening (NET) at 5 min postocclusion of the left anterior descending coronary artery in awake, unsedated dogs. Group 1 included segments with NET values of 67--100+ (percent control); group 2 between 67 and 0; and group 3 less than 0 (paradoxical motion). 5 min after coronary occlusion, group 1 NET was 92 +/- 5% (SEM) although significant decreases occurred in NET in group 2 (36 +/- 4%) and group 3 segments (-33 +/- 5%). Between 5 min and 24 h after coronary occlusion, no further significant changes occurred in NET in groups 1, 2, and 3 crystals. Some segments underwent further functional deterioration between 24 h and 1 wk after left anterior descending coronary artery occlusion, although no overall change occurred in segments with mild to moderate ischemic dysfunction. Segments with NET less than 0 at 24 h, on the other hand, exhibited a reduction in aneurysmal bulging between 24 h and 1 wk from -41 +/- 10 to -23 +/- 11% (n = 12, P = 0.02). Inotropic reserve was assessed with postextrasystolic potentiation (PESP) in 14 dogs, and with infusions of dopamine (11 dogs), and isoproterenol (13 dogs). PESP was the most potent intervention and produced a significant augmentation in NET in group 2 crystals at 1, 2, 4, 6,8, and 24 h after coronary occlusion but only at 1 and 2 h in NET in group 3 crystals. Thus, following experimental coronary occlusion, the evolution of ischemic segmental dysfunction is dynamic and variable. A significant degree of inotropic reserve, as assessed by PESP, dopamine, and isoproterenol

  5. A review of canine pseudocyesis.

    PubMed

    Gobello, C; de la Sota, R L; Goya, R G

    2001-12-01

    The purpose of this article is to review the most relevant features of the physiology, clinical signs, diagnosis, treatment and prevention of canine pseudocyesis (PSC). This is a physiological syndrome, characterized by clinical signs such as: nesting, weight gain, mammary enlargement, lactation and maternal behaviour, which appears in non-pregnant bitches at the end of metaoestrus. PSC is a frequent finding in domestic dogs. Although it is generally admitted that prolactin (PRL) plays a central role in the appearance of PSC, its precise aetiophysiology is not completely understood yet. A number of clinical studies suggest that at some point of metaoestrus circulating PRL levels rise in overtly pseudopregnant bitches. Individual differences in sensitivity to PRL as well as the existence of molecular variants of canine PRL with different bioactivity versus immunoreactivity ratios may help clarify the aetiopathology of PSC. Diagnosis of PSC is based on the presence of typical clinical signs in metaoestrous non-pregnant bitches. Considering that PSC is a self limiting physiological state, mild cases usually need no treatment. Discouraging maternal behaviour and sometimes fitting Elizabethan collars to prevent licking of the mammary glands may suffice in these cases. Sex steroids (oestrogens, progestins and androgens) have been traditionally used to treat PSC but the side-effects usually outweigh the benefits of these medications. Inhibition of PRL release by ergot derivatives [bromocriptine (10-100 microg/kg per day for 10-14 days], cabergoline (5 microg/kg per day during 5-10 days), metergoline (0.2 mg/kg per day during 8-10 days) has proved to be effective for the treatment of canine PSC. Although some of these ergot derivatives present some untoward side-effects, they are transient and can usually be managed. Predisposed bitches not intended for breeding should be spayed as ovariectomy is the only permanent preventive measure.

  6. Coagulating activity of the blood, vascular wall, and myocardium under hypodynamia conditions

    NASA Technical Reports Server (NTRS)

    Petrovskiy, B. V. (Editor); Chazov, E. I. (Editor); Andreyev, S. V. (Editor)

    1980-01-01

    In order to study the effects of hypodynamia on the coagulating properties of the blood, vascular wall, and myocardium, chinchilla rabbits were kept for varying periods in special cages which restricted their movements. At the end of the experiment, blood samples were taken and the animals were sacrificed. Preparations were made from the myocardium venae cavae, and layers of the aorta. Two resultant interrelated and mutually conditioned syndromes were discovered: thrombohemorrhagic in the blood and hemorrago-thrombotic in the tissues.

  7. Remodeling of the myocardium in early trabeculation and cardiac valve formation; a role for TGFβ2.

    PubMed

    Kruithof, Boudewijn P T; Kruithof-De-Julio, Marianna; Poelmann, Robert E; Gittenberger-De-Groot, Adriana C; Gaussin, Vinciane; Goumans, Marie-José

    2013-01-01

    Trabeculation and the formation of the leaflets of the mitral and tricuspid valves both involve remodeling of the embryonic myocardium. The nature and possible connection of these myocardial remodeling processes, however, are unclear. Therefore, we examined the morphogenesis of the early ventricular and atrioventricular (AV) myocardium and report for the first time that the formation of the early trabeculae and the positioning of the valve primordia (endocardial cushions) into the ventricular lumen are part of one continuous myocardial remodeling process, which involves the dissociation of the myocardial layers. For the endocardial cushions, this process results in delamination from the AV myocardium. The AV myocardium that will harbor the right lateral cushion is the exception and becomes positioned in the ventricular lumen by folding of the right ventricle. As a consequence, remodeling of the left and right AV myocardium occurs differently with implications for the formation of the mural leaflets and annulus fibrosis. At both the right and left side, the valvular myocardium harbors a distinct molecular phenotype and its removal from the cardiac leaflets involves a second wave of delamination. Interestingly, in the TGFβ2-KO mouse, which is a known model for cushion and valve defects, remodeling of the early myocardium is disturbed as indicated by defective trabeculae formation, persistence of valvular myocardium, disturbed myocardial phenotypes and differential defects at left and right side of the AV canal. Based on these results we propose a new model clarifying early trabeculae formation and AV valve formation and provide new inroads for an enhanced understanding of congenital heart defects.

  8. A rare cause of heart failure treated by heart transplantation: noncompaction of the ventricular myocardium.

    PubMed

    Bordes, Julien; Jop, Bertrand; Imbert, Sandrine; Hraiech, Sami; Collard, Frédéric; Kerbaul, François

    2009-01-01

    Noncompaction of the ventricular myocardium is a rare cardiomyopathy due to an arrest of myocardial morphogenesis. The characteristic echocardiographic findings are prominent myocardial trabeculations and deep intertrabecular spaces communicating with the left ventricular cavity. The clinical manifestations include heart failure (HF) signs, ventricular arrhythmias, and cardioembolic events. We describe an illustrative case of noncompaction of the ventricular myocardium associated with bicuspid aortic valve, a 42-year-old male presenting a refractory acute heart failure successfully treated by emergency heart transplantation.

  9. Drinking to near death--acute water intoxication leading to neurogenic stunned myocardium.

    PubMed

    Losonczy, Lia I; Lovallo, Emily; Schnorr, C Daniel; Mantuani, Daniel

    2016-01-01

    Neurogenic stunned myocardium is a rare disease entity that has been typically described as a consequence of subarachnoid hemorrhage and, less commonly, seizures. Here we describe a case of a healthy young woman who drank excessive free water causing acute hyponatremia complicated by cerebral edema and seizure, leading to cardiogenic shock from neurogenic stunned myocardium. Two days later, she had complete return of her normal cardiac function.

  10. [MECHANISMS OF THE EFFECT OF Li+ ON MYOCARDIUM OF VERTEBRATES].

    PubMed

    Shemarova, I V; Korotkov, S M; Nesterov, V P

    2015-01-01

    The effect of Li+ on the frog Rana temporaria myocardium and its influence on the ion transport in the rat heart mitochondria (RHM) were studied. Li+ added to the normal Ringer solution (Li(+)-R) was found to attenuate myocardial tension, decrease the maximal rate of tension development and its half-relaxation time. Comparison of the cardiac muscle contraction parameters in the Li(+)-R with the effect of the voltage-gated Ca(2+)-channels (Cav1.2), verapamil and CdCl2, showed that the negative inotropic effect of the Na+ replacement by Li+ in the limited intermembrane ("fuzzy") space is underlain by the blocking of Ca2+ influx into the myoplasm via the reverse Ca2+/Na(+)-exchanger in the plasma membrane (PM). This, in turn, prevents Ca(2+)-induced massive Ca2+ release into the myoplasm via the RYR2-channels in the sarcoplasmic reticulum (SR) leading in aggregate to suppression of Ca(2+)-dependent myocardial contractions. In the experimental studies of the Li+ effect on the RHM it was established that Li+ just slightly increases the passive permeability of the inner mitochondrial membrane (IMM) for K+ and H+ and decreases the intensity of ion pumping out of the energized mitochondrial matrix to the external medium. This may also indicate the lack of relationship between the mitochondrial oxidative processes and the reduction in the myocardial contractile activity under the Na+ replacement by Li+.

  11. Autophagy and mitophagy in the myocardium: therapeutic potential and concerns

    PubMed Central

    Jimenez, Rebecca E; Kubli, Dieter A; Gustafsson, Åsa B

    2014-01-01

    The autophagic-lysosomal degradation pathway is critical for cardiac homeostasis, and defects in this pathway are associated with development of cardiomyopathy. Autophagy is responsible for the normal turnover of organelles and long-lived proteins. Autophagy is also rapidly up-regulated in response to stress, where it rapidly clears dysfunctional organelles and cytotoxic protein aggregates in the cell. Autophagy is also important in clearing dysfunctional mitochondria before they can cause harm to the cell. This quality control mechanism is particularly important in cardiac myocytes, which contain a very high volume of mitochondria. The degradation of proteins and organelles also generates free fatty acids and amino acids, which help maintain energy levels in myocytes during stress conditions. Increases in autophagy have been observed in various cardiovascular diseases, but a major question that remains to be answered is whether enhanced autophagy is an adaptive or maladaptive response to stress. This review discusses the regulation and role of autophagy in the myocardium under baseline conditions and in various aetiologies of heart disease. It also discusses whether this pathway represents a new therapeutic target to treat or prevent cardiovascular disease and the concerns associated with modulating autophagy. Linked Articles This article is part of a themed issue on Mitochondrial Pharmacology: Energy, Injury & Beyond. To view the other articles in this issue visit http://dx.doi.org/10.1111/bph.2014.171.issue-8 PMID:24148024

  12. Hydrostatic forces limit swelling of rat ventricular myocardium.

    PubMed

    Pine, M B; Brooks, W W; Nosta, J J; Abelmann, W H

    1981-11-01

    To study ventricular cellular volume regulation when cell membranes and ion pumps cannot prevent swelling, rat ventricular sections were incubated in modified Krebs-Henseleit solutions in which 1) potassium was substituted for sodium, ion for ion; or 2) sodium chloride was reduced to decrease osmolarity to 228, 171, or 114 mosM. Ventricular water, [3H]inulin and [3H]mannitol spaces, potassium, sodium, chloride, and protein contents, and resting transmembrane potentials were measured. Increases in ventricular cellular volume were less than 30% in potassium-substituted and extremely dilute media (114 mosM), in contrast to increases of over 100% in identically treated renal cortical slices. In potassium-substituted solution, the fluid gained by ventricular cells during incubation was hypertonic with respect to the bathing medium. In dilute solution (171 and 114 mosM), ventricular, cellular, and extracellular osmolarities equilibrated only after substantial losses of cellular ions had occurred. These findings support the existence of mechanical limitations to ventricular cellular swelling, which may be caused by a unique network of interstitial collagen present in ventricular myocardium.

  13. Robust left ventricular myocardium segmentation for multi-protocol MR

    NASA Astrophysics Data System (ADS)

    Groth, A.; Weese, J.; Lehmann, H.

    2012-02-01

    For a number of cardiac procedures like the treatments of ventricular tachycardia (VT), coronary artery disease (CAD) and heart failure (HF) both anatomical as well as vitality information about the left ventricular myocardium are required. To this end, two images for the anatomical and functional information, respectively, must be acquired and analyzed, e.g. using two different 3D MR protocols. To enable automatic analysis, a workflow has been proposed1 which allows to integrate the vitality information extracted from the functional image data into a patient-specific anatomical model generated from the anatomical image. However, in the proposed workflow the extraction of accurate vitality information from the functional image depends to a large extend on the accuracy of both the anatomical model and the mapping of the model to the functional image. In this paper we propose and evaluate methods for improving these two aspects. More specifically, on one hand we aim to improve the segmentation of the often low-contrast left ventricular epicardium in the anatomical 3D MR images by introducing a patient-specific shape-bias. On the other hand, we introduce a registration approach that facilitates the mapping of the anatomical model to images acquired by different protocols and modalities, such as functional 3D MR. The new methods are evaluated on clinical MR data, for which considerable improvements can be achieved.

  14. Immunohistochemical Investigation of the Heart Allograft Myocardium (1991-1998).

    PubMed

    Beletskaya, Ludmila V.; Baranova, Flora S.; Khalimova, Zarema A.; Zaidenov, Vladimir A.; Kurenkova, Lubov G.; Kormer, Arkadiy Ya.; Khubutia, Anzor Sh.; Kupriyanova, Anna G.; Shumakov, Valeriy I.

    2000-04-01

    What is a contribution of the humoral (vascular) and mixed type of the rejection episodes to all the episodes of heart allograft rejection is not quite clear, though this factor is of considerable importance for the choice of the treatment methods. The hearts from recipients, as well as endomyocardial biopsies of the heart allografts and postmortem material were investigated with the aim to determine the immunopathological process. Overall, 420 samples from 80 patients were analyzed. Immunofluorescence examination of endomyocardial biopsy showed that in 8 from 44 patients with heart allograft in postoperative period for the first six weeks there were revealed the immunomorphological signs of the acute humoral rejection, manifested as fixation of immunoglobulins and complement in capillaries. Six of them exhibited rejection of mixed type. Most patients in the later postoperative period exhibited a discrete local fixation of immunoglobulins and complement in myocardium, that can be assessed as one of the compartments of the chronic rejection process. In cases of the secondary administration of serum preparations, the fixation of immune complexes was shown in sarcolemma and capillaries, and can be proposed as a sign of serum disease. Repeated acute rejection episodes of humoral or mixed types raised at the first six weeks after transplantation. In the period from 1-5 years after operation, patients displayed discrete deposits of the immunoglobulins and complement as part of the chronic rejection process.

  15. A pharmacological evaluation of electrical events in the myocardium.

    PubMed

    Szekeres, L

    1982-01-01

    The pharmacologist is interested in both the therapeutic effect of the drug and its mode of action. This latter is mainly studied in the isolated heart in vitro. However, in vitro experiments are not satisfactory to predict antiarrhythmic activity in vivo because: they are mostly performed in preparations made from the normal myocardium; in vitro the autonomic and hormonal effects are absent; some drugs such as nitroglycerine or strophanthin do not produce antiarrhythmic electrophysiological changes in vitro but under appropriate conditions may have a clear-cut antiarrhythmic action in vivo; and arrhythmias mostly arise from the interaction of changes in several fundamental electrophysiological parameters which could be best studied in vivo. These facts are demonstrated by the example of the pathomechanism and pharmacotherapy of early postinfarction arrhythmias. In spite of these shortcomings, there is, however, some promising development in this field. Progress is being made in the in vivo recording of electric events in the heart (multiple KCl suction electrodes, in vivo recording of Purkinje activity). Prolonged drug treatment can evoke electrophysiological changes in vitro characteristic of the action of the drug in vivo. In the donor-perfused isolated heart preparation, the drug administered to the donor animal will evoke responses in concentrations producing the in vivo effect, and the possibility of drug metabolism and binding to plasma proteins is also present.

  16. Probing myocardium biomechanics using quantitative optical coherence elastography

    NASA Astrophysics Data System (ADS)

    Wang, Shang; Lopez, Andrew L.; Morikawa, Yuka; Tao, Ge; Li, Jiasong; Larina, Irina V.; Martin, James F.; Larin, Kirill V.

    2015-03-01

    We present a quantitative optical coherence elastographic method for noncontact assessment of the myocardium elasticity. The method is based on shear wave imaging optical coherence tomography (SWI-OCT), where a focused air-puff system is used to induce localized tissue deformation through a low-pressure short-duration air stream and a phase-sensitive OCT system is utilized to monitor the propagation of the induced tissue displacement with nanoscale sensitivity. The 1-D scanning of M-mode OCT imaging and the application of optical phase retrieval and mapping techniques enable the reconstruction and visualization of 2-D depth-resolved shear wave propagation in tissue with ultra-high frame rate. The feasibility of this method in quantitative elasticity measurement is demonstrated on tissue-mimicking phantoms with the estimated Young's modulus compared with uniaxial compression tests. We also performed pilot experiments on ex vivo mouse cardiac muscle tissues with normal and genetically altered cardiomyocytes. Our results indicate this noncontact quantitative optical coherence elastographic method can be a useful tool for the cardiac muscle research and studies.

  17. Biochemical characterization of exercise-trained porcine myocardium.

    PubMed

    Laughlin, M H; Hale, C C; Novela, L; Gute, D; Hamilton, N; Ianuzzo, C D

    1991-07-01

    The purpose of this study was to determine whether cardiac biochemical adaptations are induced by chronic exercise training (ET) of miniature swine. Female Yucatan miniature swine were trained on a treadmill or were cage confined (C) for 16-22 wk. After training, the ET pigs had increased exercise tolerance, lower heart rates during exercise at submaximal intensities, moderate cardiac hypertrophy, increased coronary blood flow capacity, and increased oxidative capacity of skeletal muscle. Myosin from both the C and ET hearts was 100% of the V3 isozyme, and there were no differences between the myosin adenosine triphosphatase (ATPase) or myofibrillar ATPase activities of C and ET hearts. Also, the sarcoplasmic reticulum Ca(2+)-ATPase activity and Na(+)-Ca2+ exchange activity of sarcolemmal vesicles were the same in cardiac muscle of C and ET hearts. Finally, the glycolytic and oxidative capacity of ET cardiac muscle was not different from control, since phosphofructokinase, citrate synthase, and 3-hydroxyacyl-CoA dehydrogenase activities were the same in cardiac tissue from ET and C pigs. We conclude that endurance exercise training does not provide sufficient stress on the heart of a large mammal to induce changes in any of the three major cardiac biochemical systems of the porcine myocardium: the contractile system, the Ca2+ regulatory systems, or the metabolic system.

  18. Feasibility and safety of autologous myoblast transplantation in patients with ischemic cardiomyopathy.

    PubMed

    Dib, Nabil; McCarthy, Patrick; Campbell, Ann; Yeager, Michael; Pagani, Francis D; Wright, Susan; MacLellan, W Robb; Fonarow, Gregg; Eisen, Howard J; Michler, Robert E; Binkley, Philip; Buchele, Diane; Korn, Ronald; Ghazoul, Marwan; Dinsmore, Jonathan; Opie, Shaun R; Diethrich, Edward

    2005-01-01

    Successful autologous skeletal myoblast transplantation into infarcted myocardium in a variety of animal models has demonstrated improvement in cardiac function. We evaluated the safety and feasibility of transplanting autologous myoblasts into infarcted myocardium of patients undergoing concurrent coronary artery bypass grafting (CABG) or left ventricular assist device implantation (LVAD). In addition, we sought to gain preliminary information on graft survival and any potential improvement of cardiac function. Eighteen patients with a history of ischemic cardiomyopathy participated in a phase I, nonrandomized, multicenter pilot study of autologous skeletal myoblast transplantation concurrent with CABG or LVAD implantation. Twelve patients with a history of previous myocardial infarction (MI) and a left ventricular ejection of less than 30% were enrolled in the CABG arm. In a second arm, six patients underwent LVAD implantation as a bridge to heart transplantation and were required to donate their heart for testing at the time of heart transplant. Myoblasts were successfully transplanted in all patients without any acute injection-related complications or significant long-term unexpected adverse events. Follow-up PET scans showed new areas of viability within the infarct scar in CABG patients. Echocardiography measured an average improvement in left ventricular ejection fraction (LVEF) from 25% to 34%. Histological evaluation in four out of five patients who underwent heart transplantation documented survival and engraftment of the skeletal myoblasts within the infarcted myocardium. These interim results demonstrate survival, feasibility, and safety of autologous myoblast transplantation and suggest that this modality may offer a potential therapeutic treatment for end-stage heart disease.

  19. Prospects for improving neovascularization of the ischemic heart: Lessons from development.

    PubMed

    Smart, Nicola

    2017-01-01

    Neovascularization of the ischemic myocardium postinfarction is necessary to restore blood flow to vulnerable cardiomyocytes and will be indispensable for prospective regenerative strategies, to perfuse newly formed myocardium. Therapeutic attempts to enhance new vessel formation have, to date, yielded modest clinical benefits, and innovative approaches are now needed. Intrinsic mechanisms are initiated by the heart in an attempt to rebuild injured vessels, but these are poorly understood. Insight into the underlying mechanisms may reveal targets for therapeutically augmenting this low-level neovascular response. Starting from a limited number of descriptive studies, this review summarizes what is known of coronary neovascularization and explores putative mechanisms and cellular sources which may endogenously contribute, or that may be pharmacologically triggered, to support vasculo- or angiogenesis. As injury responses in the adult frequently recapitulate embryological processes, a particular focus is placed on the developmental mechanisms of coronary vessel formation. An understanding of the cellular sources and the regulatory pathways used by the embryo may reveal novel targets for reactivating coronary vessel and myocardial regeneration.

  20. Insulin suppresses ischemic preconditioning-mediated cardioprotection through Akt-dependent mechanisms.

    PubMed

    Fullmer, Tanner M; Pei, Shaobo; Zhu, Yi; Sloan, Crystal; Manzanares, Robert; Henrie, Brandon; Pires, Karla M; Cox, James E; Abel, E Dale; Boudina, Sihem

    2013-11-01

    It is believed that the diabetic myocardium is refractory to cardioprotection by ischemic preconditioning (IPC) mainly because of impaired insulin signaling to phosphatidylinositol 3-kinase (PI3K) and protein kinase B (PKB or Akt). However, human as well as animal studies have clearly showed that the hearts of type 2 diabetic humans and animals may exhibit increased signaling through PI3K-Akt but yet are resistant to cardioprotection by IPC or ischemic post-conditioning. Therefore, this study was designed to determine whether activation of insulin signaling prior to IPC is detrimental for cardioprotection and to assess the role of insulin receptors (IRs) and Akt in mediating this effect. Wild-type (WT) hearts, hearts lacking IRs or hearts expressing an active form of Akt (myrAkt1) were perfused ex vivo using a Langendorff preparation and were subjected to IPC (3cycles of 5min ischemia followed by 5min reflow before 30min no flow ischemia and then by 45min reperfusion) in the presence or absence of 1nmol/L insulin. Interestingly, whereas insulin was protective against I/R (30min no flow ischemia and 45min reperfusion), it completely abolished cardioprotection by IPC in WT hearts but not in mice lacking insulin receptors (IRs) in cardiomyocytes (CIRKO) or in all cardiac cells (TIRKO). The suppression of IPC-mediated cardioprotection was mediated through downstream signaling to Akt and Gsk3β. In addition, transgenic induction of Akt in the heart was sufficient to abrogate IPC even when insulin was absent, further confirming the involvement of Akt in insulin's suppression of cardioprotection by IPC. These data provide evidence that excessive insulin signaling to Akt is detrimental for cardioprotection by IPC and could explain the failure of the diabetic myocardium to precondition.

  1. Arterial ischemic stroke in HIV

    PubMed Central

    Bryer, Alan; Lucas, Sebastian; Stanley, Alan; Allain, Theresa J.; Joekes, Elizabeth; Emsley, Hedley; Turnbull, Ian; Downey, Colin; Toh, Cheng-Hock; Brown, Kevin; Brown, David; Ison, Catherine; Smith, Colin; Corbett, Elizabeth L.; Nath, Avindra; Heyderman, Robert S.; Connor, Myles D.; Solomon, Tom

    2016-01-01

    HIV infection, and potentially its treatment, increases the risk of an arterial ischemic stroke. Multiple etiologies and lack of clear case definitions inhibit progress in this field. Several etiologies, many treatable, are relevant to HIV-related stroke. To fully understand the mechanisms and the terminology used, a robust classification algorithm to help ascribe the various etiologies is needed. This consensus paper considers the strengths and limitations of current case definitions in the context of HIV infection. The case definitions for the major etiologies in HIV-related strokes were refined (e.g., varicella zoster vasculopathy and antiphospholipid syndrome) and in some instances new case definitions were described (e.g., HIV-associated vasculopathy). These case definitions provided a framework for an algorithm to help assign a final diagnosis, and help classify the subtypes of HIV etiology in ischemic stroke. PMID:27386505

  2. Canine size, shape, and bending strength in primates and carnivores.

    PubMed

    Plavcan, J Michael; Ruff, Christopher B

    2008-05-01

    Anthropoid primates are well known for their highly sexually dimorphic canine teeth, with males possessing canines that are up to 400% taller than those of females. Primate canine dimorphism has been extensively documented, with a consensus that large male primate canines serve as weapons for intrasexual competition, and some evidence that large female canines in some species may likewise function as weapons. However, apart from speculation that very tall male canines may be relatively weak and that seed predators have strong canines, the functional significance of primate canine shape has not been explored. Because carnivore canine shape and size are associated with killing style, this group provides a useful comparative baseline for primates. We evaluate primate maxillary canine tooth size, shape and relative bending strength against body size, skull size, and behavioral and demographic measures of male competition and sexual selection, and compare them to those of carnivores. We demonstrate that, relative to skull length and body mass, primate male canines are on average as large as or larger than those of similar sized carnivores. The range of primate female canine sizes embraces that of carnivores. Male and female primate canines are generally as strong as or stronger than those of carnivores. Although we find that seed-eating primates have relatively strong canines, we find no clear relationship between male primate canine strength and demographic or behavioral estimates of male competition or sexual selection, in spite of a strong relationship between these measures and canine crown height. This suggests either that most primate canines are selected to be very strong regardless of variation in behavior, or that primate canine shape is inherently strong enough to accommodate changes in crown height without compromising canine function.

  3. Evidence for canine rehabilitation and physical therapy.

    PubMed

    Millis, Darryl L; Ciuperca, Ionut Alexandru

    2015-01-01

    This article reviews some important studies regarding canine physical rehabilitation. Bones, cartilage, muscles, ligaments, and tendons undergo atrophy if loading is decreased. Knowledge of the changes that occur with immobilization and the time course of events helps in the development of a rehabilitation program to improve tissue integrity. Outcome assessment instruments are clinically useful indicators of patient progress and the success of rehabilitation programs. A number of physical modalities are used in canine rehabilitation, although there are relatively few canine-specific studies. Rehabilitation has specific benefits in the treatment of various orthopedic and neurologic conditions.

  4. Renalase protects against ischemic AKI.

    PubMed

    Lee, H Thomas; Kim, Joo Yun; Kim, Mihwa; Wang, Peili; Tang, Lieqi; Baroni, Sara; D'Agati, Vivette D; Desir, Gary V

    2013-02-01

    Elevated levels of plasma catecholamines accompany ischemic AKI, possibly contributing the inflammatory response. Renalase, an amine oxidase secreted by the proximal tubule, degrades circulating catecholamines and reduces myocardial necrosis, suggesting that it may protect against renal ischemia reperfusion injury. Here, mice subjected to renal ischemia reperfusion injury had significantly lower levels of renalase in the plasma and kidney compared with sham-operated mice. Consistent with this, plasma NE levels increased significantly after renal ischemia reperfusion injury. Furthermore, renal tubular inflammation, necrosis, and apoptosis were more severe and plasma catecholamine levels were higher in renalase-deficient mice subjected to renal ischemia reperfusion compared with wild-type mice. Administration of recombinant human renalase reduced plasma catecholamine levels and ameliorated ischemic AKI in wild-type mice. Taken together, these data suggest that renalase protects against ischemic AKI by reducing renal tubular necrosis, apoptosis, and inflammation, and that plasma renalase might be a biomarker for AKI. Recombinant renalase therapy may have potential for the prevention and treatment of AKI.

  5. Structure and vascularization of the ventricular myocardium in Holocephali: their evolutionary significance.

    PubMed

    Durán, Ana C; López-Unzu, Miguel A; Rodríguez, Cristina; Fernández, Borja; Lorenzale, Miguel; Linares, Andrea; Salmerón, Francisca; Sans-Coma, Valentín

    2015-06-01

    It was generally assumed that the ventricle of the primitive vertebrate heart was composed of trabeculated, or spongy, myocardium, supplied by oxygen-poor luminal blood. In addition, it was presumed that the mixed ventricular myocardium, consisting of a compacta and a spongiosa, and its supply through coronary arteries appeared several times throughout fish evolution. Recent work has suggested, however, that a fully vascularized, mixed myocardium may be the primitive condition in gnathostomes. The present study of the heart ventricles of four holocephalan species aimed to clarify this controversy. Our observations showed that the ventricular myocardium of Chimaera monstrosa and Harriotta raleighana consists of a very thin compacta overlying a widespread spongiosa. The ventricle of Hydrolagus affinis is composed exclusively of trabeculated myocardium. In these three species there is a well-developed coronary artery system. The main coronary artery trunks run along the outflow tract, giving off subepicardial ventricular arteries. The trabeculae of the spongiosa are irrigated by branches of the subepicardial arteries and by penetrating arterial vessels arising directly from the main coronary trunks at the level of the conoventricular junction. The ventricle of Rhinochimaera atlantica has only spongy myocardium supplied by luminal blood. Small coronary arterial vessels are present in the subepicardium, but they do not enter the myocardial trabeculae. The present findings show for the first time that in a wild living vertebrate species, specifically H. affinis, an extensive coronary artery system supplying the whole cardiac ventricle exists in the absence of a well-developed compact ventricular myocardium. This is consistent with the notion derived from experimental work that myocardial cell proliferation and coronary vascular growth rely on distinct developmental programs. Our observations, together with data in the literature on elasmobranchs, support the view that

  6. Estimating canine tooth crown height in early Australopithecus.

    PubMed

    Plavcan, J Michael; Ward, Carol V; Paulus, Faydre L

    2009-07-01

    Canine tooth size reduction and the associated reduction in canine dimorphism is a basal hominin character that also provides important evidence for models of behavioral evolution. Two specimens of Australopithecus anamensis (KNM-KP 29287 and KNM-KP 29283) that do not preserve the canine crown, but do preserve the root or alveolus, appear to suggest that canine size variation and canine dimorphism in this species may have been greater than in other hominins. We evaluate canine root and crown dimensions in a series of extant hominoids, and estimate canine crown height in Australopithecus afarensis and A. anamensis. Our results demonstrate that it is possible to generate estimates of canine crown height from basal canine crown and root dimensions with a moderate degree of accuracy. Estimates of maxillary canine crown size for A. anamensis are slightly larger than those of A. afarensis, and are approximately the same size as canines of modern female chimpanzees. Estimated mandibular canine crown height is very similar in the two species. Variation within the A. anamensis sample of estimated canine crown heights is similar to that of modern humans, suggesting a low degree of sexual dimorphism. Inclusion of estimates for KNM-KP 29287 and KNM-KP 29283 does not substantially increase either the estimate of overall canine size or variation for A. anamensis.

  7. Canine distemper virus infection of canine footpad epidermis.

    PubMed

    Gröne, Andrea; Doherr, Marcus G; Zurbriggen, Andreas

    2004-06-01

    Infection of the footpad epidermis can occur in natural canine distemper virus (CDV) infection of dogs. Footpads from 19 dogs experimentally inoculated with virulent distemper strain A75/17 and from two nonexposed dogs were examined histopathologically and assessed for the presence of viral antigen and nucleoprotein mRNA, as well as number of inflammatory and apoptotic cells. Dogs were divided into four groups based on inoculation status and postmortem examination: inoculated dogs with severe distemper (group 1, n = 7); inoculated dogs with mild distemper (group 2, n = 4); inoculated dogs without distemper (group 3, n = 8); and noninoculated dogs (group 4, n = 2). Footpads from dogs of all groups had a comparably thick epidermis. Eosinophilic viral inclusions and syncytial cells were present in footpad epidermis of one dog of group 1. Footpads of group 1 dogs contained viral antigen and mRNA in the epidermis with strongest staining in a subcorneal location. Additionally, in these dogs footpad dermal structures including eccrine glands and vascular walls were positive for virus particles. No CDV antigen or mRNA was present in the footpad epidermis and dermis of any other dog. Group 1 dogs had more CD3-positive cells and apoptotic cells within the basal layer of the epidermis when compared to the other groups. These findings demonstrate that in experimental infection CDV antigen and mRNA were colocalized in all layers of the infected canine footpad epidermis. The scarcity of overt pathological reactions with absence of keratinocyte degeneration indicates a noncytocidal persisting infection of footpad keratinocytes by CDV.

  8. Distinct microRNA expression signatures in human right atrial and ventricular myocardium.

    PubMed

    Zhang, Yangyang; Wang, Xiaowei; Xu, Xiaohan; Wang, Jun; Liu, Xiang; Chen, Yijiang

    2012-12-01

    Human atrial and ventricular myocardium has distinct structure and physiology. MicroRNAs (miRNAs) are the central players in the regulation of gene expression, participating in many physiological processes. A comprehensive knowledge of miRNA expression in the human heart is essential for the understanding of myocardial function. The aim of this study was to compare the miRNA signature in human right atrial and ventricular myocardium. Agilent human miRNA arrays were used to indicate the miRNA expression signatures of the right atrial (n = 8) and ventricular (n = 9) myocardium of healthy individuals. Quantitative reverse transcription-polymerase chain reactions (qRT-PCRs) were used to validate the array results. DIANA-mirPath was used to incorporate the miRNAs into pathways. MiRNA arrays showed that 169 miRNAs were expressed at different levels in human right atrial and ventricular myocardium. The unsupervised hierarchical clustering analysis based on the 169 dysregulated miRNAs showed that miRNA expression categorized two well-defined clusters that corresponded to human right atrial and ventricular myocardium. The qRT-PCR results correlated well with the microarray data. Bioinformatic analysis indicated the potential miRNA targets and molecular pathways. This study indicates that distinct miRNA expression signatures in human right atrial and ventricular myocardium. The findings provide a novel understanding of the molecular differences between human atrial and ventricular myocardium and may establish a framework for an anatomically detailed evaluation of cardiac function regulation.

  9. [Fractures of the canines require attention].

    PubMed

    van Foreest, Andries

    2005-01-15

    Hardly any attention was paid to a barely visible fracture of a canine tooth (104) in an 18-month-old dog. When the dog was 6-years old, a fistulous opening was seen on the bridge of the nose. A year later, radiography revealed a periapical process. The investigations performed and treatment given are described, as is the correct way to handle fractures of the canines.

  10. [Nonsurgical endodontic treatment of an invaginated canine].

    PubMed

    Fernández Guerrero, F; Miñana Laliga, R; Bullon Fernandez, P

    1989-01-01

    We present a case of a maxillary canine with a dens invaginatus treated successfully. The patient had pain, swelling and a sinus tract coming from the inmature apex of the canine. The canals were enlarged and cleaned and the main canal was filled with Calcium Hydroxide to allow the root development. Seven months later, the patient was asymptomatic and the tooth was obturated with guttapercha. One year later it was confirm the success in the treatment.

  11. Canine adenovirus type 1 in a fennec fox (Vulpes zerda).

    PubMed

    Choi, Jeong-Won; Lee, Hyun-Kyoung; Kim, Seong-Hee; Kim, Yeon-Hee; Lee, Kyoung-Ki; Lee, Myoung-Heon; Oem, Jae-Ku

    2014-12-01

    A 10-mo-old female fennec fox (Vulpes zerda) with drooling suddenly died and was examined postmortem. Histologic examination of different tissue samples was performed. Vacuolar degeneration and diffuse fatty change were observed in the liver. Several diagnostic methods were used to screen for canine parvovirus, canine distemper virus, canine influenza virus, canine coronavirus, canine parainfluenza virus, and canine adenovirus (CAdV). Only CAdV type 1 (CAdV-1) was detected in several organs (liver, lung, brain, kidney, spleen, and heart), and other viruses were not found. CAdV-1 was confirmed by virus isolation and nucleotide sequencing.

  12. CANINE: a robotic mine dog

    NASA Astrophysics Data System (ADS)

    Stancil, Brian A.; Hyams, Jeffrey; Shelley, Jordan; Babu, Kartik; Badino, Hernán.; Bansal, Aayush; Huber, Daniel; Batavia, Parag

    2013-01-01

    Neya Systems, LLC competed in the CANINE program sponsored by the U.S. Army Tank Automotive Research Development and Engineering Center (TARDEC) which culminated in a competition held at Fort Benning as part of the 2012 Robotics Rodeo. As part of this program, we developed a robot with the capability to learn and recognize the appearance of target objects, conduct an area search amid distractor objects and obstacles, and relocate the target object in the same way that Mine dogs and Sentry dogs are used within military contexts for exploration and threat detection. Neya teamed with the Robotics Institute at Carnegie Mellon University to develop vision-based solutions for probabilistic target learning and recognition. In addition, we used a Mission Planning and Management System (MPMS) to orchestrate complex search and retrieval tasks using a general set of modular autonomous services relating to robot mobility, perception and grasping.

  13. Environmental contamination by canine geohelminths.

    PubMed

    Traversa, Donato; Frangipane di Regalbono, Antonio; Di Cesare, Angela; La Torre, Francesco; Drake, Jason; Pietrobelli, Mario

    2014-02-13

    Intestinal nematodes affecting dogs, i.e. roundworms, hookworms and whipworms, have a relevant health-risk impact for animals and, for most of them, for human beings. Both dogs and humans are typically infected by ingesting infective stages, (i.e. larvated eggs or larvae) present in the environment. The existence of a high rate of soil and grass contamination with infective parasitic elements has been demonstrated worldwide in leisure, recreational, public and urban areas, i.e. parks, green areas, bicycle paths, city squares, playgrounds, sandpits, beaches. This review discusses the epidemiological and sanitary importance of faecal pollution with canine intestinal parasites in urban environments and the integrated approaches useful to minimize the risk of infection in different settings.

  14. Age estimation from canine volumes.

    PubMed

    De Angelis, Danilo; Gaudio, Daniel; Guercini, Nicola; Cipriani, Filippo; Gibelli, Daniele; Caputi, Sergio; Cattaneo, Cristina

    2015-08-01

    Techniques for estimation of biological age are constantly evolving and are finding daily application in the forensic radiology field in cases concerning the estimation of the chronological age of a corpse in order to reconstruct the biological profile, or of a living subject, for example in cases of immigration of people without identity papers from a civil registry. The deposition of teeth secondary dentine and consequent decrease of pulp chamber in size are well known as aging phenomena, and they have been applied to the forensic context by the development of age estimation procedures, such as Kvaal-Solheim and Cameriere methods. The present study takes into consideration canines pulp chamber volume related to the entire teeth volume, with the aim of proposing new regression formulae for age estimation using 91 cone beam computerized scans and a freeware open-source software, in order to permit affordable reproducibility of volumes calculation.

  15. Canine viral enteritis. Recent developments.

    PubMed

    Pollock, R V; Carmichael, L

    1979-05-01

    Two apparently novel viral gastroenteritides of dogs were recognized in 1978: one caused by a parvo-like virus (CPV) and one by a corona-like virus (CCV). A rotavirus has also been tentatively associated with neonatal pup enteritis. Canine viral enteritis is characterized by a sudden onset of vomiting and diarrhea, rapid spread and high morbidity. Treatment is only supportive but must be initiated promptly. Infected animals should be isolated immediately; the extremely contagious nature of these diseases makes them difficult to contain. Feces from infected dogs appear to be the primary means of transmission. Sodium hypochlorite solutions (eg, Clorox) are recommended for disinfection. The development of effective vaccines is an immediate and pressing problem.

  16. Biomarkers in canine parvovirus enteritis.

    PubMed

    Schoeman, J P; Goddard, A; Leisewitz, A L

    2013-07-01

    Canine parvovirus (CPV) enteritis has, since its emergence in 1978, remained a common and important cause of morbidity and mortality in young dogs. The continued incidence of parvoviral enteritis is partly due to the virus' capability to evolve into more virulent and resistant variants with significant local gastrointestinal and systemic inflammatory sequelae. This paper reviews current knowledge on historical-, signalment-, and clinical factors as well as several haematological-, biochemical- and endocrine parameters that can be used as diagnostic and prognostic biomarkers in CPV enteritis. These factors include season of presentation, purebred nature, bodyweight, vomiting, leukopaenia, lymphopaenia, thrombocytopaenia, hypercoagulability, hypercortisolaemia, hypothyroxinaemia, hypoalbuminaemia, elevated C-reactive protein and tumour necrosis factor, hypocholesterolaemia and hypocitrullinaemia. Factors contributing to the manifestations of CPV infection are multiple with elements of host, pathogen, secondary infections, underlying stressors and environment affecting severity and outcome. The availability of several prognosticators has made identification of patients at high risk of death and their subsequent targeted management more rewarding.

  17. Environmental contamination by canine geohelminths

    PubMed Central

    2014-01-01

    Intestinal nematodes affecting dogs, i.e. roundworms, hookworms and whipworms, have a relevant health-risk impact for animals and, for most of them, for human beings. Both dogs and humans are typically infected by ingesting infective stages, (i.e. larvated eggs or larvae) present in the environment. The existence of a high rate of soil and grass contamination with infective parasitic elements has been demonstrated worldwide in leisure, recreational, public and urban areas, i.e. parks, green areas, bicycle paths, city squares, playgrounds, sandpits, beaches. This review discusses the epidemiological and sanitary importance of faecal pollution with canine intestinal parasites in urban environments and the integrated approaches useful to minimize the risk of infection in different settings. PMID:24524656

  18. Genetic and Biochemical Biomarkers in Canine Glaucoma.

    PubMed

    Graham, K L; McCowan, C; White, A

    2017-03-01

    In many health-related fields, there is great interest in the identification of biomarkers that distinguish diseased from healthy individuals. In addition to identifying the diseased state, biomarkers have potential use in predicting disease risk, monitoring disease progression, evaluating treatment efficacy, and informing pathogenesis. This review details the genetic and biochemical markers associated with canine primary glaucoma. While there are numerous molecular markers (biochemical and genetic) associated with glaucoma in dogs, there is no ideal biomarker that allows early diagnosis and/or identification of disease progression. Genetic mutations associated with canine glaucoma include those affecting ADAMTS10, ADAMTS17, Myocilin, Nebulin, COL1A2, RAB22A, and SRBD1. With the exception of Myocilin, there is very limited crossover in genetic biomarkers identified between human and canine glaucomas. Mutations associated with canine glaucoma vary between and within canine breeds, and gene discoveries therefore have limited overall effects as a screening tool in the general canine population. Biochemical markers of glaucoma include indicators of inflammation, oxidative stress, serum autoantibodies, matrix metalloproteinases, tumor necrosis factor-α, and transforming growth factor-β. These markers include those that indicate an adaptive or protective response, as well as those that reflect the damage arising from oxidative stress.

  19. Prevalence of asymmetric molar and canine relationship.

    PubMed

    Behbehani, Faraj; Roy, Rino; Al-Jame, Badreia

    2012-12-01

    The purpose of this study was to investigate the prevalence and severity of occlusal asymmetries in the molar and canine regions in a large population-based sample of adolescent Kuwaitis. Using a stratified cluster sampling method, 1299 Kuwaiti adolescents (674 boys mean age 13.3 years and 625 girls mean age 13.2 years), representing approximately 6.7 per cent of that age stratum in the population, were examined clinically for sagittal molar and canine relationships, with a view to recording half and full-step asymmetries. In this sample, 1244 subjects were examined clinically, while for the remaining 55, pre-treatment study models were assessed. All subjects were in the early permanent dentition stage. Descriptive statistical analyses were used to determine the proportion of different molar and canine asymmetries. Antero-posterior asymmetries were found to be a distinctive and common feature of the dental arches, with half-step outweighing full-step asymmetries both in the anterior and posterior regions. The total prevalence of an asymmetric molar or canine relationship was 29.7 and 41.4 per cent, respectively, with more than 95 per cent falling in the mild category. Patient gender did not influence the prevalence or magnitude of asymmetry. The results showed a clinically significant prevalence of asymmetric molar and canine relationships, which were mainly in the category of half-step asymmetry. Class II half and full-step asymmetries were more prevalent than Class III asymmetries in the molar and canine regions.

  20. [The application of hemoreologic indicators in prognosis of complications of acute myocardium infarction].

    PubMed

    Pakhrova, O A; Kudriashova, M V; Grineva, M R; Mishina, I E

    2015-02-01

    The sampling of 60 patients with acute myocardium infarction underwent a complex study of hemoreologic indicators with purpose to establish predictors of development of early complications of diseases to substantiate additions to algorithm of examination and to differentiate treatment regimens. It is established that under acute myocardium infarction the blood viscosity increases on low velocity of shifting and plasma. Also, the process of aggregation of erythrocytes increases and number of normocytes decreases without significant alterations of blood viscosity on high velocity of shift and capacity of erythrocytes to be distorted. At the same time, the mentioned above alterations in patients with acute myocardium infarction does not result in decreasing of effectiveness oftransportation of oxygen to tissues. Against the background of development the hemoreologic disorders have more apparent character and result in progressive decreasing of tissue perfusion. The most significant prognostic indicator concerning complications of acute myocardium infarction is a time parameter of increment of aggregation of erythrocytes surpassing 2.80 in 89% of patients with complications. The expedience of inclusion of detection of reologic blood indicators fir their subsequent correction in the complex of examination ofpatients with acute myocardium infarction.

  1. Resistance of contracting myocardium to swelling with hypoxia and glycolytic blockade.

    PubMed

    Pine, M B; Caulfield, J B; Bing, O H; Brooks, W W; Abelmann, W H

    1979-04-01

    The interrelationship of myocardial metabolism, performance and tissue hydration was examined in isolated contracting rat, guinea pig and dog myocardium. Myocardial metabolism was altered by blocking aerobic, and both aerobic and anaerobic metabolism. Myocardial water content and distribution were measured in rat myocardium using 3H-inulin and 51Cr-EDTA as extracellular markers. Myocardial hydration was also evaluated by light and electron microscopy. The relative susceptibility of non-contracting slices of rat and guinea pig myocardium and kidney to swelling secondary to these interventions was also explored. Hypoxia resulted in a partially reversible reduction in mechanical function; hypoxia plus glycolytic blockade led to irreversible severe contracture and total loss of tension development. Neither hypoxia nor hypoxia plus glycolytic blockade resulted in increased total tissue or extracellular water in previously contracting preparations or in non-contracting slices of myocardium. On the other hand, there were significant increases in cellular water in similarly treated kidney slices after each intervention. Thus, despite severe, irreversible derangements of mechanical function, myocardium did not swell under conditions which produced swelling in renal cortex.

  2. Patency of heart blood vessels under photosensitization reaction shortly after intravenous injection of talaporfin sodium in canine model

    NASA Astrophysics Data System (ADS)

    Hamada, Risa; Matsuzaki, Ryota; Ogawa, Emiyu; Arai, Tsunenori

    2016-03-01

    In order to investigate patency of heart blood vessels by photosensitization reaction shortly after intravenous injection of talaporfin sodium, we performed in vitro endothelial cell lethality study and in vivo study of heart blood vessel patency in canine one week after photosensitization reaction. Cell lethality of human umbilical vein endothelial cells under different albumin concentrations corresponding with blood and interstice concentrations were employed and their lethality 2 hours after the reaction was measured by WST assay in vitro. Almost all cells survived by 40 J/cm2 photosensitization reaction with blood albumin concentration. Laser diffuser made of plastic optical fiber with 70 mm in length was used in vivo. Red diode laser of 664nm wavelength was emitted from this diffuser with 17.1-42.9 mW/cm in 10 minutes. We estimated the fluence rate distribution by a ray-trace simulator using pre-measured optical coefficients of myocardium tissue, μa 0.12 mm-1 and μs' 0.36 mm-1. Almost all blood vessels were patent in every irradiation conditions in canine heart. Coronary artery and vein up to 1 mm diameter were patent in typical myocardium sample with 25.7 mW/cm. We estimated fluence rate distribution of this sample and found that blood vessels were patent even fluence rate over 40 J/cm2. This in vivo study could be explained by the result of in vitro study. We suggest that this blood vessel patency after our particular photosensitization reaction might be because of few photosensitizer uptake in the blood endothelial cells and/or reduced oxidation damage by thick albumin concentration in blood.

  3. Correlated response, competition, and female canine size in primates.

    PubMed

    Plavcan, J M

    1998-12-01

    Recently, comparative analyses of female canine tooth size in primates have yielded two hypotheses to explain interspecific variation in female relative canine size. Greenfield ([1992] Int. J. Primatol. 13:631-657; [1992] Yrbk. Phys. Anthropol. 35:153-184; [1996] J. Hum. Evol. 31:1-19) suggested that covariation in male and female canine size across species indicates that female canine size reflects correlated response (in which the expression of a trait in one sex causes the expression of the same trait in the other sex). Plavcan et al. ([1995] J. Hum. Evol. 28:245-276) noted that female canine size in primates is associated with variation in categorical estimates of the intensity of female-female agonistic competition, suggesting that selection favors large female canine size in many species. While it may seem that the two models are in conflict, they are not. To simultaneously evaluate these two models, this analysis examines the joint relations between male canine size, female canine size, and estimates of female-female competition in a sample of 108 primate species. Overall, female canine size is correlated with variation in male canine size. Controlling for variation in male canine size, female canine size is also correlated with estimates of the intensity of female-female agonistic competition. The relation between these variables differs strongly between anthropoid and strepsirhine primates. In anthropoids, the data suggest that selection for the development of large canines in females is not constrained by any affect of correlated response. In strepsirhines, the evidence suggests that sexual selection may affect male canine size but that correlated response affects female canine size, resulting in monomorphism for most species. These observations help reconcile the observations of Greenfield ([1992] Int. J. Primatol. 13:631-657; [1996] J. Hum. Evol. 31:1-19) and Plavcan et al. ([1995] J. Hum. Evol. 28:245-276) and provide a more precise model for

  4. Factors affecting self-eruption of displaced permanent maxillary canines.

    PubMed

    Smailienė, Dalia; Sidlauskas, Antanas; Lopatienė, Kristina; Guzevičienė, Vesta; Juodžbalys, Gintaras

    2011-01-01

    The aim of this study was to examine the possibility of the spontaneous eruption of displaced unerupted maxillary canines after the extraction of the deciduous canine and dental arch expansion and to determine the impact of initial canine position on treatment success rate. Materials and METHODS. The study sample included 50 patients (mean age, 13.5 years [SD, 2.2]) with unilaterally displaced unerupted maxillary canines. Deciduous canines were extracted, and the space for displaced canine was created at the beginning of the study. The follow-up period for the spontaneous eruption was 12 months. The initial vertical, horizontal, labio-palatal position and angle of inclination to the midline of the displaced canine were assessed on panoramic radiographs. RESULTS. Only 42% of displaced canines erupted spontaneously within one-year period (52.9% of labially displaced canines and 36.4% of palatally displaced canines). A significant difference of inclination was determined between spontaneously erupted and unerupted teeth in the labially displaced canine group (P<0.01), with no difference in the palatally displaced canine group. The receiver operating characteristic curve analysis showed that the critical angle of inclination for the spontaneous eruption of the retained canine was 20º (sensitivity 0.759; specificity 0.571; P<0.05). The majority of unerupted canines (75.9%) were inclined more than 20º. The initial height of canine was crucial for spontaneous eruption (sensitivity 0.966; specificity 0.81; P<0.001). This was true for both palatal and labial cases. CONCLUSIONS. The initial vertical position of the labially and palatally displaced canines and the inclination of the labially displaced canines were the most important predictors for spontaneous eruption of the cuspid.

  5. Role of canine circovirus in dogs with acute haemorrhagic diarrhoea.

    PubMed

    Anderson, A; Hartmann, K; Leutenegger, C M; Proksch, A L; Mueller, R S; Unterer, S

    2017-02-27

    Canine circovirus (CanineCV) has been detected in some dogs with severe haemorrhagic diarrhoea, but its pathogenic role is unclear. This study evaluated a suspected association between the presence of CanineCV and acute haemorrhagic diarrhoea syndrome (AHDS) in dogs. The prevalence of CanineCV in dogs with AHDS was compared with that in healthy dogs and those infected with canine parvovirus (CPV). Additionally, time to recovery and mortality rate were compared between CanineCV-positive and CanineCV-negative dogs. Faecal samples of dogs with AHDS (n=55), healthy dogs (n=66) and dogs infected with CPV (n=54) were examined by two real-time TaqMan PCR assays targeting the replicase and capsid genes of CanineCV. CanineCV was detected in faecal samples of two dogs with AHDS, three healthy controls and seven dogs infected with CPV. Among the three groups, there was no significant difference in prevalence of CanineCV. CPV-infected animals that were coinfected with CanineCV had a significantly higher mortality rate compared with those negative for CanineCV. CanineCV does not appear to be the primary causative agent of AHDS in dogs, but might play a role as a negative co-factor in disease outcome in dogs with CPV infection.

  6. Identification of cardiac progenitors that survive in the ischemic human heart after ventricular myocyte death

    PubMed Central

    Omatsu-Kanbe, Mariko; Nozuchi, Nozomi; Nishino, Yuka; Mukaisho, Ken-ichi; Sugihara, Hiroyuki; Matsuura, Hiroshi

    2017-01-01

    Atypically-shaped cardiomyocytes (ACMs) are beating heart cells identified in the cultures of cardiomyocyte-removed fractions obtained from adult mouse hearts. Since ACMs spontaneously develop into beating cells in the absence of hormones or chemicals, these cells are likely to be a type of cardiac progenitors rather than stem cells. “Native ACMs” are found as small interstitial cells among ventricular myocytes that co-express cellular prion protein (PrP) and cardiac troponin T (cTnT) in mouse and human heart tissues. However, the endogenous behavior of human ACMs is unclear. In the present study, we demonstrate that PrP+ cTnT+ cells are present in the human heart tissue with myocardial infarction (MI). These cells were mainly found in the border of necrotic cardiomyocytes caused by infarcts and also in the hibernating myocardium subjected to the chronic ischemia. The ratio of PrP+ cTnT+ cells to the total cells observed in the normal heart tissue section of mouse and human was estimated to range from 0.3–0.8%. Notably, living human PrP+ cTnT+ cells were identified in the cultures obtained at pathological autopsy despite exposure to lethal ischemic conditions for hours after death. These findings suggest that ACMs could survive in the ischemic human heart and develop into a sub-population of cardiac myocytes. PMID:28120944

  7. Healthy aging and myocardium: A complicated process with various effects in cardiac structure and physiology.

    PubMed

    Nakou, E S; Parthenakis, F I; Kallergis, E M; Marketou, M E; Nakos, K S; Vardas, P E

    2016-04-15

    It is known that there is an ongoing increase in life expectancy worldwide, especially in the population older than 65years of age. Cardiac aging is characterized by a series of complex pathophysiological changes affecting myocardium at structural, cellular, molecular and functional levels. These changes make the aged myocardium more susceptible to stress, leading to a high prevalence of cardiovascular diseases (heart failure, atrial fibrillation, left ventricular hypertrophy, coronary artery disease) in the elderly population. The aging process is genetically programmed but modified by environmental influences, so that the rate of aging can vary widely among people. We summarized the entire data concerning all the multifactorial changes in aged myocardium and highlighting the recent evidence for the pathophysiological basis of cardiac aging. Keeping an eye on the clinical side, this review will explore the potential implications of the age-related changes in the clinical management and on novel therapeutic strategies potentially deriving from the scientific knowledge currently acquired on cardiac aging process.

  8. Serological detection of infection with canine distemper virus, canine parvovirus and canine adenovirus in communal dogs from Zimbabwe.

    PubMed

    McRee, Anna; Wilkes, Rebecca P; Dawson, Jessica; Parry, Roger; Foggin, Chris; Adams, Hayley; Odoi, Agricola; Kennedy, Melissa A

    2014-09-05

    Domestic dogs are common amongst communities in sub-Saharan Africa and may serve as important reservoirs for infectious agents that may cause diseases in wildlife. Two agents of concern are canine parvovirus (CPV) and canine distemper virus (CDV), which may infect and cause disease in large carnivore species such as African wild dogs and African lions, respectively. The impact of domestic dogs and their diseases on wildlife conservation is increasing in Zimbabwe, necessitating thorough assessment and implementation of control measures. In this study, domestic dogs in north-western Zimbabwe were evaluated for antibodies to CDV, CPV, and canine adenovirus (CAV). These dogs were communal and had no vaccination history. Two hundred and twenty-five blood samples were collected and tested using a commercial enzyme-linked immunosorbent assay (ELISA) for antibodies to CPV, CDV, and CAV. Of these dogs, 75 (34%) had detectable antibodies to CDV, whilst 191 (84%) had antibodies to CPV. Antibodies to canine adenovirus were present in 28 (13%) dogs. Canine parvovirus had high prevalence in all six geographic areas tested. These results indicate that CPV is circulating widely amongst domestic dogs in the region. In addition, CDV is present at high levels. Both pathogens can infect wildlife species. Efforts for conservation of large carnivores in Zimbabwe must address the role of domestic dogs in disease transmission.

  9. Expression of major gap junction connexin types in the working myocardium of eight chordates.

    PubMed

    Becker, D L; Cook, J E; Davies, C S; Evans, W H; Gourdie, R G

    1998-01-01

    The alpha1 connexin (connexin43) is regarded as the major gap junction protein of the myocardium because it predominates there in mammals. Here, we show that it is not the major connexin of the working myocardium in non-mammalian vertebrates, which instead express beta1-like connexins homologous to mammalian connexin32. A phylogenetic series of hearts was immunostained with seven antibodies raised against peptide sequences specific for three distinct members of the gap junction connexin family: alpha1, beta1 and alpha5 (mammalian connexin40/avian connexin42). Working myocardium from two ascidian chordates (Ciona and Mogula), a teleost (Carassius), a frog (Xenopus) and two reptiles (Anolis and Alligator) was found to express a beta1-like connexin, rather than an alpha1-like connexin. An alpha1-like connexin was nevertheless often detected in other cardiac tissues. In the chicken (by ancestry a reptile), the developing myocardium expressed a beta1-like connexin strongly on embryonic day 6 but less strongly at hatching, and minimally in the adult. Myocardial expression of alpha5 connexin increased during development, but remained strongest in the coronary vascular endothelial and cardiac conduction tissues. The arteriolar smooth muscle of the chicken expressed alpha1 connexin throughout development, but its myocardium did not. In contrast, the working myocardium of a marsupial mammal (the opossum Trichosurus) strongly expressed an alpha1 connexin just like placental mammals. These results imply that a shift from beta1 to alpha1 connexin expression in the heart occurred prior to the evolution of the opossums. The beta and alpha connexin subfamilies have different permeabilities and gating properties, and we discuss factors that might have made this shift beneficial.

  10. VEGF-C/VEGFR-3 pathway promotes myocyte hypertrophy and survival in the infarcted myocardium

    PubMed Central

    Zhao, Tieqiang; Zhao, Wenyuan; Meng, Weixin; Liu, Chang; Chen, Yuanjian; Gerling, Ivan C; Weber, Karl T; Bhattacharya, Syamal K; Kumar, Rahul; Sun, Yao

    2015-01-01

    Background: Numerous studies have shown that in addition to angio/lymphangiogenesis, the VEGF family is involved in other cellular actions. We have recently reported that enhanced VEGF-C and VEGFR-3 in the infarcted rat myocardium, suggesting the paracrine/autocrine function of VEGF-C on cardiac remodeling. The current study was designed to test the hypothesis that VEGF-C regulates cardiomyocyte growth and survival in the infarcted myocardium. Methods and results: Gene profiling and VEGFR-3 expression of cardiomyocytes were assessed by laser capture microdissection/microarray and immunohistochemistry in the normal and infarcted myocardium. The effect of VEGF-C on myocyte hypertrophy and apoptosis during normoxia and hypoxia was detected by RT-PCR and western blotting in cultured rat neonatal cardiomyocytes. VEGFR-3 was minimally expressed in cardiomyocytes of the normal and noninfarcted myocardium, while markedly elevated in the surviving cardiomyocytes of the infarcted myocardium and border zone. Genes altered in the surviving cardiomyocytes were associated with the networks regulating cellular growth and survival. VEGF-C significantly increased the expression of atrial natriuretic factor (ANP), brain natriuretic factor (BNP), and β-myosin heavy chain (MHC), markers of hypertrophy, in neonatal cardiomyocytes. Hypoxia caused neonatal cardiomyocyte atrophy, which was prevented by VEGF-C treatment. Hypoxia significantly enhanced apoptotic mediators, including cleaved caspase 3, 8, and 9, and Bax in neonatal cardiomyocytes, which were abolished by VEGF-C treatment. Conclusion: Our findings indicate that VEGF-C/VEGFR-3 pathway exerts a beneficial role in the infarcted myocardium by promoting compensatory cardiomyocyte hypertrophy and survival. PMID:26064438

  11. Mechanisms of action of diltiazem in isolated human atrial and ventricular myocardium.

    PubMed

    Sutton, M S; Morad, M

    1987-05-01

    A comparative study of human atrial fibers (HAF), human ventricular fibers (HVF), frog ventricle, and frog skeletal muscle demonstrated marked differences in tension development in the presence of diltiazem. There was no significant difference between the tension developed by HAF and by HVF over a range of diltiazem concentrations when the differences in resting membrane potential were corrected by increasing external K+ concentration. In human myocardium, diltiazem resulted in both a voltage and use-dependent blockade of the calcium channel. Comparison of the tension-dose response curves in human myocardium, frog ventricle and skeletal muscle showed that diltiazem was most effective at decreasing tension in frog heart, and least effective in skeletal muscle with human myocardium being intermediate. In skeletal muscle, neither tension development nor the birefringence signal related to the Ca2+ release from the sarcoplasmic reticulum was significantly altered by Diltiazem in concentrations less than 10(-6) M, but in concentrations greater than 10(-5) M both were suppressed. Diltiazem suppressed tension in human myocardium over the range of membrane potentials associated with Ca2+ channel activity, while at more positive potentials, diltiazem appeared to have little effect on the tension-voltage relations. Diltiazem had no effect upon tension development induced by acetyl strophanthidin in human myocardium or upon the Ca2+ sensitivity of chemically skinned atrial or ventricular fibers. Thus the tension-suppressant effect of diltiazem in human myocardium appears to be mediated by a combination of voltage-dependent block of the Ca2+ channel and inhibition of Ca2+ release from internal stores, and not from alterations in either Na+-Ca2+ coupled transport or Ca2+ sensitivity of the myofilaments.

  12. Hyperspectral imaging of ischemic wounds

    NASA Astrophysics Data System (ADS)

    Gnyawali, Surya C.; Elgharably, Haytham; Melvin, James; Huang, Kun; Bergdall, Valerie; Allen, David W.; Hwang, Jeeseong; Litorja, Maritoni; Shirley, Eric; Sen, Chandan K.; Xu, Ronald

    2012-03-01

    Optical imaging has the potential to achieve high spatial resolution and high functional sensitivity in wound assessment. However, clinical acceptance of many optical imaging devices is hampered by poor reproducibility, low accuracy, and lack of biological interpretation. We developed an in vivo model of ischemic flap for non-contact assessment of wound tissue functional parameters and spectral characteristics. The model was created by elevating the bipedicle skin flaps of a domestic pig from the underlying vascular bed and inhibiting graft bed reperfusion by a silastic sheet. Hyperspectral imaging was carried out on the ischemic flap model and compared with transcutaneous oxygen tension and perfusion measurements at different positions of the wound. Hyperspectral images have also been captured continuously during a post-occlusive reactive hyperemia (PORH) procedure. Tissue spectral characteristics obtained by hyperspectral imaging correlated well with cutaneous tissue oxygen tension, blood perfusion, and microscopic changes of tissue morphology. Our experiments not only demonstrated the technical feasibility for quantitative assessment of chronic wound but also provided a potential digital phantom platform for quantitative characterization and calibration of medical optical devices.

  13. Canine distemper virus infection: proliferation of canine footpad keratinocytes.

    PubMed

    Gröne, A; Engelhardt, P; Zurbriggen, A

    2003-09-01

    The proliferation of footpad keratinocytes of canine distemper virus (CDV)-infected dogs was investigated. Footpads of 19 dogs inoculated experimentally with a virulent distemper strain (A75/17) and of two noninoculated control dogs were collected at necropsy. Dogs were divided into four groups according to results of the postmortem examination: dogs with severe distemper (group 1), dogs with mild distemper (group 2), inoculated dogs without distemper (group 3) and noninoculated dogs (group 4). There was no distinct difference of epidermal thickness among the four groups. Infection of the footpad epidermis with CDV was demonstrated using immunohistochemistry for viral nucleoprotein and in situ hybridization for nucleoprotein messenger ribonucleic acid (mRNA). Only group 1 dogs had viral antigen and mRNA in the footpad epidermis with the same distribution. Footpad epidermis of group 1 dogs had more mitotic figures in the basal layer, and significantly more basal keratinocytes were positive for the proliferation markers Ki-67 and proliferating cell nuclear antigen. Double-staining for Ki-67 and viral nucleoprotein identified rare double-labeled basal keratinocytes. These findings suggest that the presence of CDV particles in the footpad epidermis is associated with keratinocyte proliferation.

  14. Free Radical Oxidation in Rat Myocardium after Maximum Permissible Hepatic Resection.

    PubMed

    Ermolaev, P A; Khramykh, T P; Barskaya, L O

    2016-03-01

    Free radical oxidation in rat myocardial homogenate was studied by chemiluminescent assay during the early terms after maximum permissible liver resection. During this period, activation of free radical oxidation was biphasic. The critical terms characterized by dramatic intensification of free radical oxidation in the myocardium are the first hour and the first day after surgery. The period from 3 to 12 h after surgery, in which the indices of chemiluminescence decrease, can be tentatively termed as the period of "putative wellbeing". Normalization of the free radical oxidation processes in the myocardium occurred by day 7 after surgery.

  15. Accurate harmonic phase tracking of tagged MRI using locally-uniform myocardium displacement constraint.

    PubMed

    ElDeeb, Safaa M; Fahmy, Ahmed S

    2016-11-01

    Harmonic phase (HARP) tracking is one of the most commonly used techniques for estimating the myocardium regional function from tagged cardiac Magnetic Resonance Imaging sequences. Nevertheless, tag fading and phase distortion can severely limit the tracking accuracy of the technique. In this work, we propose to modify the HARP tracking algorithm to impose a constraint of locally uniform displacement field while tracking the different myocardium points. A numerical contracting phantom and a dataset of 11 patients are used to study the performance of the proposed technique at the different cardiac phases, slices, and regions. The results show that the proposed method improves the tracking accuracy and the reliability of the conventional HARP technique.

  16. Scale-selective analysis of myocardium polarization images in problems of diagnostic of necrotic changes

    NASA Astrophysics Data System (ADS)

    Ushenko, O. G.; Dubolazov, O. V.; Ushenko, Yu. O.; Gorsky, M. P.

    2015-11-01

    This research presents the results of investigation of laser polarization fluorescence of biological layers (histological sections of the myocardium). The polarized structure of autofluorescence imaging layers of biological tissues was detected and investigated. Proposed the model of describing the formation of polarization inhomogeneous of autofluorescence imaging biological optically anisotropic layers. On this basis, analytically and experimentally tested to justify the method of laser polarimetry autofluorescent. Analyzed the effectiveness of of this method in the postmortem diagnosis of infarction. The objective criteria (statistical moments) of differentiation of autofluorescent images of histological sections myocardium were defined. The operational characteristics (sensitivity, specificity, accuracy) of these technique were determined.

  17. Statistical and fractal analysis of autofluorescent myocardium images in posthumous diagnostics of acute coronary insufficiency

    NASA Astrophysics Data System (ADS)

    Boichuk, T. M.; Bachinskiy, V. T.; Vanchuliak, O. Ya.; Minzer, O. P.; Garazdiuk, M.; Motrich, A. V.

    2014-08-01

    This research presents the results of investigation of laser polarization fluorescence of biological layers (histological sections of the myocardium). The polarized structure of autofluorescence imaging layers of biological tissues was detected and investigated. Proposed the model of describing the formation of polarization inhomogeneous of autofluorescence imaging biological optically anisotropic layers. On this basis, analytically and experimentally tested to justify the method of laser polarimetry autofluorescent. Analyzed the effectiveness of this method in the postmortem diagnosis of infarction. The objective criteria (statistical moments) of differentiation of autofluorescent images of histological sections myocardium were defined. The operational characteristics (sensitivity, specificity, accuracy) of these technique were determined.

  18. 9 CFR 113.316 - Canine Parainfluenza Vaccine.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 9 Animals and Animal Products 1 2012-01-01 2012-01-01 false Canine Parainfluenza Vaccine. 113.316... Virus Vaccines § 113.316 Canine Parainfluenza Vaccine. Canine Parainfluenza Vaccine shall be prepared... immunogenic shall be used for preparing seeds for vaccine production. All serials of vaccine shall be...

  19. 9 CFR 113.316 - Canine Parainfluenza Vaccine.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 9 Animals and Animal Products 1 2011-01-01 2011-01-01 false Canine Parainfluenza Vaccine. 113.316... Virus Vaccines § 113.316 Canine Parainfluenza Vaccine. Canine Parainfluenza Vaccine shall be prepared... immunogenic shall be used for preparing seeds for vaccine production. All serials of vaccine shall be...

  20. 9 CFR 113.316 - Canine Parainfluenza Vaccine.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Canine Parainfluenza Vaccine. 113.316... Virus Vaccines § 113.316 Canine Parainfluenza Vaccine. Canine Parainfluenza Vaccine shall be prepared... immunogenic shall be used for preparing seeds for vaccine production. All serials of vaccine shall be...

  1. 9 CFR 113.201 - Canine Distemper Vaccine, Killed Virus.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 9 Animals and Animal Products 1 2014-01-01 2014-01-01 false Canine Distemper Vaccine, Killed Virus... REQUIREMENTS Killed Virus Vaccines § 113.201 Canine Distemper Vaccine, Killed Virus. Canine Distemper Vaccine... been established as pure, safe, and immunogenic shall be used for vaccine production. All serials...

  2. 9 CFR 113.306 - Canine Distemper Vaccine.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 9 Animals and Animal Products 1 2012-01-01 2012-01-01 false Canine Distemper Vaccine. 113.306... Virus Vaccines § 113.306 Canine Distemper Vaccine. Canine Distemper Vaccine shall be prepared from virus... as pure, safe, and immunogenic shall be used for preparing the production seed virus for...

  3. 9 CFR 113.306 - Canine Distemper Vaccine.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 9 Animals and Animal Products 1 2011-01-01 2011-01-01 false Canine Distemper Vaccine. 113.306... Virus Vaccines § 113.306 Canine Distemper Vaccine. Canine Distemper Vaccine shall be prepared from virus... as pure, safe, and immunogenic shall be used for preparing the production seed virus for...

  4. 9 CFR 113.306 - Canine Distemper Vaccine.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 9 Animals and Animal Products 1 2014-01-01 2014-01-01 false Canine Distemper Vaccine. 113.306... Virus Vaccines § 113.306 Canine Distemper Vaccine. Canine Distemper Vaccine shall be prepared from virus... as pure, safe, and immunogenic shall be used for preparing the production seed virus for...

  5. 9 CFR 113.201 - Canine Distemper Vaccine, Killed Virus.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Canine Distemper Vaccine, Killed Virus... REQUIREMENTS Killed Virus Vaccines § 113.201 Canine Distemper Vaccine, Killed Virus. Canine Distemper Vaccine... been established as pure, safe, and immunogenic shall be used for vaccine production. All serials...

  6. 9 CFR 113.316 - Canine Parainfluenza Vaccine.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 9 Animals and Animal Products 1 2013-01-01 2013-01-01 false Canine Parainfluenza Vaccine. 113.316... Virus Vaccines § 113.316 Canine Parainfluenza Vaccine. Canine Parainfluenza Vaccine shall be prepared... immunogenic shall be used for preparing seeds for vaccine production. All serials of vaccine shall be...

  7. 9 CFR 113.306 - Canine Distemper Vaccine.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 9 Animals and Animal Products 1 2013-01-01 2013-01-01 false Canine Distemper Vaccine. 113.306... Virus Vaccines § 113.306 Canine Distemper Vaccine. Canine Distemper Vaccine shall be prepared from virus... as pure, safe, and immunogenic shall be used for preparing the production seed virus for...

  8. 9 CFR 113.201 - Canine Distemper Vaccine, Killed Virus.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 9 Animals and Animal Products 1 2012-01-01 2012-01-01 false Canine Distemper Vaccine, Killed Virus... REQUIREMENTS Killed Virus Vaccines § 113.201 Canine Distemper Vaccine, Killed Virus. Canine Distemper Vaccine... been established as pure, safe, and immunogenic shall be used for vaccine production. All serials...

  9. 9 CFR 113.201 - Canine Distemper Vaccine, Killed Virus.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 9 Animals and Animal Products 1 2013-01-01 2013-01-01 false Canine Distemper Vaccine, Killed Virus... REQUIREMENTS Killed Virus Vaccines § 113.201 Canine Distemper Vaccine, Killed Virus. Canine Distemper Vaccine... been established as pure, safe, and immunogenic shall be used for vaccine production. All serials...

  10. 9 CFR 113.201 - Canine Distemper Vaccine, Killed Virus.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 9 Animals and Animal Products 1 2011-01-01 2011-01-01 false Canine Distemper Vaccine, Killed Virus... REQUIREMENTS Killed Virus Vaccines § 113.201 Canine Distemper Vaccine, Killed Virus. Canine Distemper Vaccine... been established as pure, safe, and immunogenic shall be used for vaccine production. All serials...

  11. 9 CFR 113.306 - Canine Distemper Vaccine.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Canine Distemper Vaccine. 113.306... Virus Vaccines § 113.306 Canine Distemper Vaccine. Canine Distemper Vaccine shall be prepared from virus... as pure, safe, and immunogenic shall be used for preparing the production seed virus for...

  12. 9 CFR 113.316 - Canine Parainfluenza Vaccine.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 9 Animals and Animal Products 1 2014-01-01 2014-01-01 false Canine Parainfluenza Vaccine. 113.316... Virus Vaccines § 113.316 Canine Parainfluenza Vaccine. Canine Parainfluenza Vaccine shall be prepared... immunogenic shall be used for preparing seeds for vaccine production. All serials of vaccine shall be...

  13. Reduction of ischemic myocardial damage in the dog by lidocaine infusion.

    PubMed Central

    Schaub, R. G.; Stewart, G.; Strong, M.; Ruotolo, R.; Lemoie, G.

    1977-01-01

    The effects of lidocaine infusion on the ultrastructural damage induced in cardiac muscle by normothermic cardiopulmonary bypass were assessed in 15 dogs. Six dogs received no medication other than sodium pentobarbital (25 mg/kg, intravenously) while 9 dogs were treated with lidocaine after anesthesia. Lidocaine was given as a 2-mg/kg loading dose 10 minutes prior to ischemic arrest and a 2-mg/min continuous infusion during the entire experimental period. Biopsy samples of the left ventricular apex were taken 15 and 45 minutes after the start of ischemic arrest and 5 minutes after resumption of coronary blood flow. Biopsy samples were also obtained from 4 animals after thoracotomy to serve as controls for experimental procedures. Myocardial ultrastructure in the 4 control animals was comparable to that reported by other investigators. Five of 6 of the nontreated dogs and 8 of 9 lidocaine-treated dogs survived the entire period of ischemia and 5 minutes of coronary reperfusion. However, the extent of ultrastructural damage varied considerably between the two groups. In the experimental dogs receiving no lidocaine, mitochondria were swollen, cristae were absent, the mitochondrial matrix was cleared, and sarcomeres were disrupted. Myelin figures and contraction bands were also observed. None of the surviving lidocaine-treated animals had ultrastructural changes comparable to the worst ones in nontreated dogs. Damage was limited to some swelling of mitochondria with focal clearing of matrix. Most cristae remained intact. There were no myelin figures and few contraction bands. The results suggest that lidocaine protects the integrity of ischemic myocardium. It is suggested that this protection resulted from stabilization of plasma and/or mitochondrial membranes. (Am J Pathol 87:399-414, 1977). Images Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Figure 1 Figure 2 PMID:851172

  14. Cardiomyocyte mitochondria as targets of humoral factors released by remote ischemic preconditioning

    PubMed Central

    Gedik, Nilguen; Maciel, Leonardo; Schulte, Christiane; Skyschally, Andreas; Heusch, Gerd

    2016-01-01

    Introduction Remote ischemic preconditioning (RIPC) reduces myocardial infarct size, and protection can be transferred with plasma to other individuals, even across species. Mitochondria are the end-effectors of cardioprotection by local ischemic conditioning maneuvers. We have now analyzed mitochondrial function in response to RIPC. Material and methods Plasma from pigs undergoing placebo or RIPC (infarct size reduction by 67% in RIPC pigs compared to placebo) was transferred to isolated perfused rat hearts subjected to 30 min global ischemia followed by 120 min reperfusion for infarct size measurement. Additional experiments were terminated at 10 min reperfusion to isolate mitochondria for functional measurements. Effects of RIPC pig plasma were compared to local ischemic preconditioning (IPC) or to infusion of tumor necrosis factor α (TNF-α). Results Ischemia/reperfusion (I/R) induced an infarct of 41 ±2% of total ventricular mass. Placebo pig plasma did not affect infarct size (38 ±1, p = 0.13). The RIPC pig plasma reduced infarct size (27 ±2, p < 0.001), as did IPC (20 ±1, p < 0.001) and TNF-α (28 ±2, p < 0.001). Associated with cardioprotection, reductions of mitochondrial adenosine diphosphate (ADP)-stimulated respiration, adenosine triphosphate (ATP) production and calcium retention capacity (CRC) by I/R and placebo pig plasma were prevented by RIPC pig plasma, as they were by IPC and TNF-α. Mitochondrial reactive oxygen species production (nmol H2O2/100 µg protein) induced by I/R (272 ±34) was comparable in response to placebo pig plasma (234 ±28, p = 0.37) and was reduced by RIPC pig plasma (83 ±15, p < 0.001) as well as by IPC (78 ±21, p < 0.001) and TNF-α (125 ±42, p = 0.002). Conclusions In rat myocardium, mitochondria are an intracellular target of protection induced by humoral factors retrieved from pigs undergoing RIPC. PMID:28261301

  15. Antibody titers for canine parvovirus type-2, canine distemper virus, and canine adenovirus type-1 in adult household dogs.

    PubMed

    Taguchi, Masayuki; Namikawa, Kazuhiko; Maruo, Takuya; Orito, Kensuke; Lynch, Jonathan; Sahara, Hiroeki

    2011-09-01

    Serum antibody titers for canine parvovirus type-2 (CPV-2), canine distemper virus (CDV) and canine adenovirus type-1 (CAV-1) were investigated in 1031 healthy adult household dogs (2 to 18 years old) given an annual inoculation in the previous 11 to 13 months. The number of dogs retaining significant titers of antibodies against CPV-2, CDV, and CAV-1 were 888 (86%), 744 (72%), and 732 (71%), respectively. There were no differences between males and females in antibody titers against the 3 viruses. Antibody titer for CPV-2 was significantly higher in younger dogs than in older dogs, CDV antibody was significantly higher in older dogs than in younger dogs, and CAV titer was not associated with age.

  16. Antibody titers for canine parvovirus type-2, canine distemper virus, and canine adenovirus type-1 in adult household dogs

    PubMed Central

    Taguchi, Masayuki; Namikawa, Kazuhiko; Maruo, Takuya; Orito, Kensuke; Lynch, Jonathan; Sahara, Hiroeki

    2011-01-01

    Serum antibody titers for canine parvovirus type-2 (CPV-2), canine distemper virus (CDV) and canine adenovirus type-1 (CAV-1) were investigated in 1031 healthy adult household dogs (2 to 18 years old) given an annual inoculation in the previous 11 to 13 months. The number of dogs retaining significant titers of antibodies against CPV-2, CDV, and CAV-1 were 888 (86%), 744 (72%), and 732 (71%), respectively. There were no differences between males and females in antibody titers against the 3 viruses. Antibody titer for CPV-2 was significantly higher in younger dogs than in older dogs, CDV antibody was significantly higher in older dogs than in younger dogs, and CAV titer was not associated with age. PMID:22379198

  17. Booster effect of canine distemper, canine parvovirus infection and infectious canine hepatitis combination vaccine in domesticated adult dogs.

    PubMed

    Taguchi, Masayuki; Namikawa, Kazuhiko; Maruo, Takuya; Orito, Kensuke; Lynch, Jonathan; Tsuchiya, Ryo; Sahara, Hiroeki

    2012-08-01

    Domesticated adult dogs with antibody titer classified as below 'high' to one or more of canine distemper virus (CDV), canine parvovirus type-2 (CPV-2) and canine adenovirus type-1 (CAdV-1) were then given an additional inoculation, and the effectiveness of this booster evaluated 2 months later. Consequently, CDV and CAdV-1 antibody titer experienced a significant increase, but the same effect was not observed in the antibody titer of CPV-2. These findings suggest that with additional inoculation, a booster effect may be expected in increasing antibody titers for CDV and CAdV-1, but it is unlikely to give an increase in CPV-2 antibody titer.

  18. Orthodontic Traction of Impacted Canine Using Cantilever

    PubMed Central

    Gonçalves, João Roberto; Cassano, Daniel Serra; Bianchi, Jonas

    2016-01-01

    The impaction of the maxillary canines causes relevant aesthetic and functional problems. The multidisciplinary approach to the proper planning and execution of orthodontic traction of the element in question is essential. Many strategies are cited in the literature; among them is the good biomechanical control in order to avoid possible side effects. The aim of this paper is to present a case report in which a superior canine impacted by palatine was pulled out with the aid of the cantilever on the Segmented Arch Technique (SAT) concept. A 14.7-year-old female patient appeared at clinic complaining about the absence of the upper right permanent canine. The proposed treatment prioritized the traction of the upper right canine without changing the occlusion and aesthetics. For this, it only installed the upper fixed appliance (Roth with slot 0.018), opting for SAT in order to minimize unwanted side effects. The use of cantilever to the traction of the upper right canine has enabled an efficient and predictable outcome, because it is of statically determined mechanics. PMID:27800192

  19. Canine kobuvirus infections in Korean dogs.

    PubMed

    Oem, Jae-Ku; Choi, Jeong-Won; Lee, Myoung-Heon; Lee, Kyoung-Ki; Choi, Kyoung-Seong

    2014-10-01

    To investigate canine kobuvirus (CaKoV) infection, fecal samples (n = 59) were collected from dogs with or without diarrhea (n = 21 and 38, respectively) in the Republic of Korea (ROK) in 2012. CaKoV infection was detected in four diarrheic samples (19.0 %) and five non-diarrheic samples (13.2 %). All CaKoV-positive dogs with diarrhea were found to be infected in mixed infections with canine distemper virus and canine parvovirus or canine adenovirus. There was no significant difference in the prevalence of CaKoV in dogs with and without diarrhea. By phylogenetic analysis based on partial 3D genes and complete genome sequences, the Korean isolates were found to be closely related to each other regardless of whether they were associated with diarrhea, and to the canine kobuviruses identified in the USA and UK. This study supports the conclusion that CaKoVs from different countries are not restricted geographically and belong to a single lineage.

  20. Erythropoietin: Powerful Protection of Ischemic and Post-Ischemic Brain

    PubMed Central

    Nguyen, Anh Q.; Cherry, Brandon H.; Scott, Gary F.; Ryou, Myoung-Gwi; Mallet, Robert T.

    2015-01-01

    Ischemic brain injury inflicted by stroke and cardiac arrest ranks among the leading causes of death and long-term disability in the United States. The brain consumes large amounts of metabolic substrates and oxygen to sustain its energy requirements. Consequently, the brain is exquisitely sensitive to interruptions in its blood supply, and suffers irreversible damage after 10–15 minutes of severe ischemia. Effective treatments to protect the brain from stroke and cardiac arrest have proven elusive, due to the complexities of the injury cascades ignited by ischemia and reperfusion. Although recombinant tissue plasminogen activator and therapeutic hypothermia have proven efficacious for stroke and cardiac arrest, respectively, these treatments are constrained by narrow therapeutic windows, potentially detrimental side effects and the limited availability of hypothermia equipment. Mounting evidence demonstrates the cytokine hormone erythropoietin (EPO) to be a powerful neuroprotective agent and a potential adjuvant to established therapies. Classically, EPO originating primarily in the kidneys promotes erythrocyte production by suppressing apoptosis of proerythroid progenitors in bone marrow. However, the brain is capable of producing EPO, and EPO’s membrane receptors and signaling components also are expressed in neurons and astrocytes. EPO activates signaling cascades that increase the brain’s resistance to ischemia-reperfusion stress by stabilizing mitochondrial membranes, limiting formation of reactive oxygen and nitrogen intermediates, and suppressing pro-inflammatory cytokine production and neutrophil infiltration. Collectively, these mechanisms preserve functional brain tissue and, thus, improve neurocognitive recovery from brain ischemia. This article reviews the mechanisms mediating EPO-induced brain protection, critiques the clinical utility of exogenous EPO to preserve brain threatened by ischemic stroke and cardiac arrest, and discusses the

  1. Targeting neonatal ischemic brain injury with a pentapeptide-based irreversible caspase inhibitor

    PubMed Central

    Chauvier, D; Renolleau, S; Holifanjaniaina, S; Ankri, S; Bezault, M; Schwendimann, L; Rousset, C; Casimir, R; Hoebeke, J; Smirnova, M; Debret, G; Trichet, A-P; Carlsson, Y; Wang, X; Bernard, E; Hébert, M; Rauzier, J-M; Matecki, S; Lacampagne, A; Rustin, P; Mariani, J; Hagberg, H; Gressens, P; Charriaut-Marlangue, C; Jacotot, E

    2011-01-01

    Brain protection of the newborn remains a challenging priority and represents a totally unmet medical need. Pharmacological inhibition of caspases appears as a promising strategy for neuroprotection. In a translational perspective, we have developed a pentapeptide-based group II caspase inhibitor, TRP601/ORPHA133563, which reaches the brain, and inhibits caspases activation, mitochondrial release of cytochrome c, and apoptosis in vivo. Single administration of TRP601 protects newborn rodent brain against excitotoxicity, hypoxia–ischemia, and perinatal arterial stroke with a 6-h therapeutic time window, and has no adverse effects on physiological parameters. Safety pharmacology investigations, and toxicology studies in rodent and canine neonates, suggest that TRP601 is a lead compound for further drug development to treat ischemic brain damage in human newborns. PMID:21881605

  2. Canine and feline abortion diagnostics.

    PubMed

    Schlafer, D H

    2008-08-01

    Knowledge of the causes of canine or feline pregnancy loss is limited and the success rate for making a definitive diagnosis is disappointingly low. Although these facts are discouraging, there are some things that can be done to improve success rates. This paper will address limitations and explore ways for improvement. For abortions caused by microbial infections, there are many reasons why it may not possible to identify the agents. "Non-infectious" causes are much more difficult to diagnose, and their relative importance is unknown. These include endocrine failure, underlying endometrial disease, genetic abnormalities, nutritional deficiencies, and toxicosis from drugs or environmental sources. Genetic abnormalities are a major cause of human pregnancy loss, yet we have little specific information about genetic diseases leading to abortion in animals. This paper addresses ways clinicians and diagnosticians can work together to improve diagnostic success. Necropsy techniques for fetal and placental examination and sampling are briefly reviewed. It is hoped that this series of papers will stimulate discussion on the causes and pathogenesis of pregnancy failure, and focus attention on areas where abortion diagnostics can be improved.

  3. Conditions associated with canine hypothyroidism.

    PubMed

    Panciera, D L

    2001-09-01

    Careful review of the literature regarding clinical signs caused by hypothyroidism in dogs has shown that some assumptions regarding the relation of hypothyroidism to other conditions are based on anecdotal evidence. Cutaneous manifestations are present in most hypothyroid dogs, but the specific abnormalities and breed variations remain to be clearly defined. Decreased metabolic rate manifested by obesity and lethargy is also common. Neurologic manifestations, although uncommon, clearly occur in hypothyroid dogs. Cardiac abnormalities seem to be common, but their clinical significance is questionable. The only consistent hematologic abnormality that occurs in hypothyroid dogs is anemia; evidence for acquired von Willebrand's disease or other bleeding disorders is negligible. Reproductive dysfunction secondary to hypothyroidism is unlikely to occur in male dogs, and there is no evidence to support abnormalities in female dogs. The relation of megaesophagus, laryngeal paralysis, ocular abnormalities, and gastrointestinal disorders with hypothyroidism remains to be established. Future research into canine hypothyroidism may serve to convert dogma into a more clear understanding of the manifestations and pathophysiologic findings of this common endocrinopathy.

  4. Canine pyometra: What is new?

    PubMed

    Hagman, R

    2016-11-03

    Pyometra is a common disease in countries where elective spaying is not routinely performed. Hormonal and bacterial factors are fundamental in the pathogenesis of the disease, which manifests itself as a potentially life-threatening bacterial infection of the uterus. Surgical ovariohysterectomy is the safest and most effective treatment for pyometra, and it has recently been shown that laparoscopically assisted methods for surgical treatment are feasible to use in selected cases. New protocols for improved medical treatment alternatives have also been tested with promising results. To be able to predict outcome and presence of complications early would be valuable in clinical practice for optimizing therapy and increasing survival. Results of commonly investigated clinical and laboratory investigations have been shown to be useful as predictive markers, with leucopenia being associated with increased risk of peritonitis as well as prolonged post-operative hospitalization after surgical treatment. A cage-side rapid and cost-effective diagnostic test would be highly valuable in clinical practice, and detection of pyometra-specific upregulated genes in the uterus and the corresponding products is a potential start in identifying novel markers suitable for such as test. The focus of the present review is to highlight recent findings on pathogenesis, prediction of outcome, diagnosis and treatment. Additionally, central research questions and suggestions for future investigations about several aspects of canine pyometra will be addressed.

  5. Mortality increases after massive exchange transfusion with older stored blood in canines with experimental pneumonia.

    PubMed

    Solomon, Steven B; Wang, Dong; Sun, Junfeng; Kanias, Tamir; Feng, Jing; Helms, Christine C; Solomon, Michael A; Alimchandani, Meghna; Quezado, Martha; Gladwin, Mark T; Kim-Shapiro, Daniel B; Klein, Harvey G; Natanson, Charles

    2013-02-28

    Two-year-old purpose-bred beagles (n = 24) infected with Staphylococcus aureus pneumonia were randomized in a blinded fashion for exchange transfusion with either 7- or 42-day-old canine universal donor blood (80 mL/kg in 4 divided doses). Older blood increased mortality (P = .0005), the arterial alveolar oxygen gradient (24-48 hours after infection; P ≤ .01), systemic and pulmonary pressures during transfusion (4-16 hours) and pulmonary pressures for ~ 10 hours afterward (all P ≤ .02). Further, older blood caused more severe lung damage, evidenced by increased necrosis, hemorrhage, and thrombosis (P = .03) noted at the infection site postmortem. Plasma cell–free hemoglobin and nitric oxide (NO) consumption capability were elevated and haptoglobin levels were decreased with older blood during and for 32 hours after transfusion (all P ≤ .03). The low haptoglobin (r = 0.61; P = .003) and high NO consumption levels at 24 hours (r = −0.76; P < .0001) were associated with poor survival. Plasma nontransferrin-bound and labile iron were significantly elevated only during transfusion (both P = .03) and not associated with survival (P = NS). These data from canines indicate that older blood after transfusion has a propensity to hemolyze in vivo, releases vasoconstrictive cell-free hemoglobin over days, worsens pulmonary hypertension, gas exchange, and ischemic vascular damage in the infected lung, and thereby increases the risk of death from transfusion.

  6. Canine Rabies Ecology in Southern Africa

    PubMed Central

    2005-01-01

    Rabies is a widespread disease in African domestic dogs and certain wild canine populations. Canine rabies became established in Africa during the 20th century, coinciding with ecologic changes that favored its emergence in canids. I present a conceptual and terminologic framework for understanding rabies ecology in African canids. The framework is underpinned by 2 distinct concepts: maintenance and persistence. Maintenance encompasses the notion of indefinite transmission of infection within a local population and depends on an average transmission ratio >1. Maintenance in all local populations is inherently unstable, and the disease frequently becomes extinct. Persistence, the notion of long-term continuity, depends on the presence of rabies in >1 local population within the canine metapopulation at any time. The implications for understanding rabies ecology and control are reviewed, as are previous studies on rabies ecology in African canids. PMID:16229759

  7. Cardiac Ventricular HIFU: Convergence of Experiment and Theory in the Canine Model

    NASA Astrophysics Data System (ADS)

    Muratore, Robert; Abe, Yukio; Homma, Shunichi; Bernardi, Richard; Kalisz, Andrew; Feleppa, Ernest J.

    2007-05-01

    OBJECTIVE: HIFU is a promising technique for treating cardiac ventricular diseases such as sustained ventricular tachycardia. Ablations can potentially destroy arrhythmogenic foci and block reentrant circuits. Towards this end, we have learned to control HIFU lesions in the canine model in vivo. METHODS: Experiment — Thoracotomies were performed on anesthetized dogs, following IACUC guidelines. In this open-chest configuration, a polyethylene water-filled bag was coupled to the myocardium with degassed ultrasound gel. The transducer was lowered into the water. Ventricular locations were targeted and insonified with multiple 200-ms HIFU bursts of 60-W acoustic power; the bursts were triggered with the electrocardiogram QRS complex. The therapeutic transducer was a 35-mm focal length, 33-mm diameter PZT annular array, excited at 5.25 MHz. Its -3dB focal region dimensions were 2.5 mm axially and 0.3 mm transversely. A confocal diagnostic transducer was used for aiming and for recording backscattered radiofrequency ultrasound data. Theory — A comprehensive acoustic model has been developed. Individual modules numerically simulate physical processes such as ultrasound beam propagation, energy transfer, and heat flow within tissue. One set of modules simulates HIFU ablation in moving tissue. Tissue motion was obtained from digitized B-mode videos of transverse cross sections of a beating canine heart. Epicardial and endocardial surface positions were extracted from the video frames. Additional simulations of static tissue compared linear and nonlinear propagation models. RESULTS: Significant agreement between simulated and measured lesion sizes and between linear and nonlinear propagation models was demonstrated.

  8. The sinus venosus myocardium contributes to the atrioventricular canal: potential role during atrioventricular node development?

    PubMed

    Kelder, Tim P; Vicente-Steijn, Rebecca; Harryvan, Tom J; Kosmidis, Georgios; Gittenberger-de Groot, Adriana C; Poelmann, Rob E; Schalij, Martin J; DeRuiter, Marco C; Jongbloed, Monique R M

    2015-06-01

    The presence of distinct electrophysiological pathways within the atrioventricular node (AVN) is a prerequisite for atrioventricular nodal reentrant tachycardia to occur. In this study, the different cell contributions that may account for the anatomical and functional heterogeneity of the AVN were investigated. To study the temporal development of the AVN, the expression pattern of ISL1, expressed in cardiac progenitor cells, was studied in sequential stages performing co-staining with myocardial markers (TNNI2 and NKX2-5) and HCN4 (cardiac conduction system marker). An ISL1+/TNNI2+/HCN4+ continuity between the myocardium of the sinus venosus and atrioventricular canal was identified in the region of the putative AVN, which showed a pacemaker-like phenotype based on single cell patch-clamp experiments. Furthermore, qPCR analysis showed that even during early development, different cell populations can be identified in the region of the putative AVN. Fate mapping was performed by in ovo vital dye microinjection. Embryos were harvested and analysed 24 and 48 hrs post-injection. These experiments showed incorporation of sinus venosus myocardium in the posterior region of the atrioventricular canal. The myocardium of the sinus venosus contributes to the atrioventricular canal. It is postulated that the myocardium of the sinus venosus contributes to nodal extensions or transitional cells of the AVN since these cells are located in the posterior region of the AVN. This finding may help to understand the origin of atrioventricular nodal reentrant tachycardia.

  9. Oncolytic virotherapy of canine and feline cancer.

    PubMed

    Gentschev, Ivaylo; Patil, Sandeep S; Petrov, Ivan; Cappello, Joseph; Adelfinger, Marion; Szalay, Aladar A

    2014-05-16

    Cancer is the leading cause of disease-related death in companion animals such as dogs and cats. Despite recent progress in the diagnosis and treatment of advanced canine and feline cancer, overall patient treatment outcome has not been substantially improved. Virotherapy using oncolytic viruses is one promising new strategy for cancer therapy. Oncolytic viruses (OVs) preferentially infect and lyse cancer cells, without causing excessive damage to surrounding healthy tissue, and initiate tumor-specific immunity. The current review describes the use of different oncolytic viruses for cancer therapy and their application to canine and feline cancer.

  10. Canine olfactory detection of malignant melanoma

    PubMed Central

    Campbell, Leon Frederick; Farmery, Luke; George, Susannah Mary Creighton; Farrant, Paul B J

    2013-01-01

    Our patient is a 75-year-old man who presented after his pet dog licked persistently at an asymptomatic lesion behind his right ear. Examination revealed a nodular lesion in the postauricular sulcus. Histology confirmed malignant melanoma, which was subsequently excised. Canine olfactory detection of human malignancy is a well-documented phenomenon. Advanced olfaction is hypothesised to explain canine detection of bladder, breast, colorectal, lung, ovarian, prostate and skin cancers. Further research in this area may facilitate the development of a highly accurate aid to diagnosis for many malignancies, including melanoma. PMID:24127369

  11. Oncolytic Virotherapy of Canine and Feline Cancer

    PubMed Central

    Gentschev, Ivaylo; Patil, Sandeep S.; Petrov, Ivan; Cappello, Joseph; Adelfinger, Marion; Szalay, Aladar A.

    2014-01-01

    Cancer is the leading cause of disease-related death in companion animals such as dogs and cats. Despite recent progress in the diagnosis and treatment of advanced canine and feline cancer, overall patient treatment outcome has not been substantially improved. Virotherapy using oncolytic viruses is one promising new strategy for cancer therapy. Oncolytic viruses (OVs) preferentially infect and lyse cancer cells, without causing excessive damage to surrounding healthy tissue, and initiate tumor-specific immunity. The current review describes the use of different oncolytic viruses for cancer therapy and their application to canine and feline cancer. PMID:24841386

  12. Canine parvovirus enteritis, canine distemper, and major histocompatibility complex genetic variation in Mexican wolves.

    PubMed

    Hedrick, Philip W; Lee, Rhonda N; Buchanan, Colleen

    2003-10-01

    The endangered Mexican wolf (Canis lupus baileyi) was recently reintroduced into Arizona and New Mexico (USA). In 1999 and 2000, pups from three litters that were part of the reintroduction program died of either canine parvovirus or canine distemper. Overall, half (seven of 14) of the pups died of either canine parvovirus or canine distemper. The parents and their litters were analyzed for variation at the class II major histocompatibility complex (MHC) gene DRB1. Similar MHC genes are related to disease resistance in other species. All six of the surviving pups genotyped for the MHC gene were heterozygous while five of the pups that died were heterozygous and one was homozygous. Resistance to pathogens is an important aspect of the management and long-term survival of endangered taxa, such as the Mexican wolf.

  13. Serologic response of maned wolves (Chrysocyon brachyurus) to canine and canine parvovirus vaccination distemper virus.

    PubMed

    Maia, O B; Gouveia, A M

    2001-03-01

    This study evaluated the immune response of 47 (22 males, 25 females) captive maned wolves (Chrysocyon brachyurus) to modified-live canine parvovirus and canine distemper virus (Onderstepoort and Rockborn strains) vaccines. Sera were collected from 33 adults and 14 pups, including five free-ranging pups captured at 1 yr of age or younger. All the adults and four captive-born pups had been vaccinated prior to this first blood collection. Virus neutralization and hemagglutination-inhibition assays were performed for quantitating antibodies against canine distemper and canine parvovirus, respectively. Distemper antibody titers > or = 100 were present in 57% of adults and 14% of pups. All adults and 29% of pups had parvovirus antibody titers > or = 80. After vaccination, 72% of the wolves developed antibody titers > or = 100 against distemper and 98% developed titers > or = 80 against parvovirus. Both vaccines used were safe and immunogenic to juvenile and adult maned wolves, regardless of prior vaccination history.

  14. The Seroprevalence of Canine Parvovirus-2 in a Selected Sample of the Canine Population in Ontario

    PubMed Central

    Carman, P. S.; Povey, R. C.

    1984-01-01

    Canine sera, collected from dogs presented to the Ontario Veterinary College between 1976 and 1980, were assessed for canine parvovirus-2 antibody using a microtitre hemagglutination-inhibition test. Special emphasis was made on the period from September 1979 to October 1980 (2892 samples). No antibody was detected in samples collected in 1976 or 1977. The first positive sera were obtained in January 1978. By the end of 1978 antibodies to canine parvovirus-2 were widespread in Ontario dogs and in 1980, 683 of 2191 dogs (31.2%) had antibody. This was before widespread vaccination was being practised and indicates canine parvovirus-2 infection occurred frequently. Evaluation of clinical records of these dogs suggested that most infections had been subclinical. PMID:17422418

  15. Decline of Phosphotransfer and Substrate Supply Metabolic Circuits Hinders ATP Cycling in Aging Myocardium

    PubMed Central

    Nemutlu, Emirhan; Gupta, Anu; Zhang, Song; Viqar, Maria; Holmuhamedov, Ekhson; Terzic, Andre; Jahangir, Arshad; Dzeja, Petras

    2015-01-01

    Integration of mitochondria with cytosolic ATP-consuming/ATP-sensing and substrate supply processes is critical for muscle bioenergetics and electrical activity. Whether age-dependent muscle weakness and increased electrical instability depends on perturbations in cellular energetic circuits is unknown. To define energetic remodeling of aged atrial myocardium we tracked dynamics of ATP synthesis-utilization, substrate supply, and phosphotransfer circuits through adenylate kinase (AK), creatine kinase (CK), and glycolytic/glycogenolytic pathways using 18O stable isotope-based phosphometabolomic technology. Samples of intact atrial myocardium from adult and aged rats were subjected to 18O-labeling procedure at resting basal state, and analyzed using the 18O-assisted HPLC-GC/MS technique. Characteristics for aging atria were lower inorganic phosphate Pi[18O], γ-ATP[18O], β-ADP[18O], and creatine phosphate CrP[18O] 18O-labeling rates indicating diminished ATP utilization-synthesis and AK and CK phosphotransfer fluxes. Shift in dynamics of glycolytic phosphotransfer was reflected in the diminished G6P[18O] turnover with relatively constant glycogenolytic flux or G1P[18O] 18O-labeling. Labeling of G3P[18O], an indicator of G3P-shuttle activity and substrate supply to mitochondria, was depressed in aged myocardium. Aged atrial myocardium displayed reduced incorporation of 18O into second (18O2), third (18O3), and fourth (18O4) positions of Pi[18O] and a lower Pi[18O]/γ-ATP[18 O]-labeling ratio, indicating delayed energetic communication and ATP cycling between mitochondria and cellular ATPases. Adrenergic stress alleviated diminished CK flux, AK catalyzed β-ATP turnover and energetic communication in aging atria. Thus, 18O-assisted phosphometabolomics uncovered simultaneous phosphotransfer through AK, CK, and glycolytic pathways and G3P substrate shuttle deficits hindering energetic communication and ATP cycling, which may underlie energetic vulnerability of aging

  16. Decline of Phosphotransfer and Substrate Supply Metabolic Circuits Hinders ATP Cycling in Aging Myocardium.

    PubMed

    Nemutlu, Emirhan; Gupta, Anu; Zhang, Song; Viqar, Maria; Holmuhamedov, Ekhson; Terzic, Andre; Jahangir, Arshad; Dzeja, Petras

    2015-01-01

    Integration of mitochondria with cytosolic ATP-consuming/ATP-sensing and substrate supply processes is critical for muscle bioenergetics and electrical activity. Whether age-dependent muscle weakness and increased electrical instability depends on perturbations in cellular energetic circuits is unknown. To define energetic remodeling of aged atrial myocardium we tracked dynamics of ATP synthesis-utilization, substrate supply, and phosphotransfer circuits through adenylate kinase (AK), creatine kinase (CK), and glycolytic/glycogenolytic pathways using 18O stable isotope-based phosphometabolomic technology. Samples of intact atrial myocardium from adult and aged rats were subjected to 18O-labeling procedure at resting basal state, and analyzed using the 18O-assisted HPLC-GC/MS technique. Characteristics for aging atria were lower inorganic phosphate Pi[18O], γ-ATP[18O], β-ADP[18O], and creatine phosphate CrP[18O] 18O-labeling rates indicating diminished ATP utilization-synthesis and AK and CK phosphotransfer fluxes. Shift in dynamics of glycolytic phosphotransfer was reflected in the diminished G6P[18O] turnover with relatively constant glycogenolytic flux or G1P[18O] 18O-labeling. Labeling of G3P[18O], an indicator of G3P-shuttle activity and substrate supply to mitochondria, was depressed in aged myocardium. Aged atrial myocardium displayed reduced incorporation of 18O into second (18O2), third (18O3), and fourth (18O4) positions of Pi[18O] and a lower Pi[18O]/γ-ATP[18 O]-labeling ratio, indicating delayed energetic communication and ATP cycling between mitochondria and cellular ATPases. Adrenergic stress alleviated diminished CK flux, AK catalyzed β-ATP turnover and energetic communication in aging atria. Thus, 18O-assisted phosphometabolomics uncovered simultaneous phosphotransfer through AK, CK, and glycolytic pathways and G3P substrate shuttle deficits hindering energetic communication and ATP cycling, which may underlie energetic vulnerability of aging

  17. Mesenchymal stem cell-loaded cardiac patch promotes epicardial activation and repair of the infarcted myocardium.

    PubMed

    Wang, Qiang-Li; Wang, Hai-Jie; Li, Zhi-Hua; Wang, Yong-Li; Wu, Xue-Ping; Tan, Yu-Zhen

    2017-02-28

    Cardiac patch is considered a promising strategy for enhancing stem cell therapy of myocardial infarction (MI). However, the underlying mechanisms for cardiac patch repairing infarcted myocardium remain unclear. In this study, we investigated the mechanisms of PCL/gelatin patch loaded with MSCs on activating endogenous cardiac repair. PCL/gelatin patch was fabricated by electrospun. The patch enhanced the survival of the seeded MSCs and their HIF-1α, Tβ4, VEGF and SDF-1 expression and decreased CXCL14 expression in hypoxic and serum-deprived conditions. In murine MI models, the survival and distribution of the engrafted MSCs and the activation of the epicardium were examined, respectively. At 4 weeks after transplantation of the cell patch, the cardiac functions were significantly improved. The engrafted MSCs migrated across the epicardium and into the myocardium. Tendency of HIF-1α, Tβ4, VEGF, SDF-1 and CXCL14 expression in the infarcted myocardium was similar with expression in vitro. The epicardium was activated and epicardial-derived cells (EPDCs) migrated into deep tissue. The EPDCs differentiated into endothelial cells and smooth muscle cells, and some of EPDCs showed to have differentiated into cardiomyocytes. Density of blood and lymphatic capillaries increased significantly. More c-kit(+) cells were recruited into the infarcted myocardium after transplantation of the cell patch. The results suggest that epicardial transplantation of the cell patch promotes repair of the infarcted myocardium and improves cardiac functions by enhancing the survival of the transplanted cells, accelerating locality paracrine, and then activating the epicardium and recruiting endogenous c-kit(+) cells. Epicardial transplantation of the cell patch may be applied as a novel effective MI therapy.

  18. Advancing functional engineered cardiac tissues toward a preclinical model of human myocardium

    PubMed Central

    Turnbull, Irene C.; Karakikes, Ioannis; Serrao, Gregory W.; Backeris, Peter; Lee, Jia-Jye; Xie, Chaoqin; Senyei, Grant; Gordon, Ronald E.; Li, Ronald A.; Akar, Fadi G.; Hajjar, Roger J.; Hulot, Jean-Sébastien; Costa, Kevin D.

    2014-01-01

    Cardiac experimental biology and translational research would benefit from an in vitro surrogate for human heart muscle. This study investigated structural and functional properties and interventional responses of human engineered cardiac tissues (hECTs) compared to human myocardium. Human embryonic stem cell-derived cardiomyocytes (hESC-CMs, >90% troponin-positive) were mixed with collagen and cultured on force-sensing elastomer devices. hECTs resembled trabecular muscle and beat spontaneously (1.18±0.48 Hz). Microstructural features and mRNA expression of cardiac-specific genes (α-MHC, SERCA2a, and ACTC1) were comparable to human myocardium. Optical mapping revealed cardiac refractoriness with loss of 1:1 capture above 3 Hz, and cycle length dependence of the action potential duration, recapitulating key features of cardiac electrophysiology. hECTs reconstituted the Frank-Starling mechanism, generating an average maximum twitch stress of 660 μN/mm2 at Lmax, approaching values in newborn human myocardium. Dose-response curves followed exponential pharmacodynamics models for calcium chloride (EC50 1.8 mM) and verapamil (IC50 0.61 μM); isoproterenol elicited a positive chronotropic but negligible inotropic response, suggesting sarcoplasmic reticulum immaturity. hECTs were amenable to gene transfer, demonstrated by successful transduction with Ad.GFP. Such 3-D hECTs recapitulate an early developmental stage of human myocardium and promise to offer an alternative preclinical model for cardiology research.—Turnbull, I. C., Karakikes, I., Serrao, G. W., Backeris, P., Lee, J.-J., Xie, C., Senyei, G., Gordon, R. E., Li, R. A., Akar, F. G., Hajjar, R. J., Hulot, J.-S., Costa, K. D. Advancing functional engineered cardiac tissues toward a preclinical model of human myocardium. PMID:24174427

  19. Forty years of canine vaccination.

    PubMed

    Appel, M J

    1999-01-01

    During the last 40 years vaccines have been developed that have greatly reduced the incidence of infectious diseases of dogs. In general, modified live products have been superior to inactivated vaccines for dogs. It can be expected that recombinant and/or DNA vaccines may dominate the market in the future. Although most vaccines on the market are safe and efficacious, there have been exceptions where disease was induced by vaccination or dogs were not protected. The failure of protection may in part be due to variations in individual vaccine batches. Only potency tests but not efficacy tests are required, which may not be sufficient. For example, a virus titer in a vaccine may be meaningless if the minimum protective dose is not known. Overattenuated virus (e.g., CDV-Ond or parvovirus in cat cells) may have a high titer in tissue culture but is not immunogenic. The question of frequency of vaccination of dogs should be addressed. Annual revaccinations for CDV, CPV, and CAV are probably not needed. However, it would be desirable to collect more data to support less frequent vaccinations. Annual immunization for bacterial diseases such as kennel cough, Lyme disease, and leptospirosis should continue. It also would be desirable to develop more oro/nasal vaccines, perhaps combined with newly developed vectors that are less likely to induce undesirable side effects that may be seen after parenteral vaccination. Finally a word of warning against homeopathic "nosodes" to replace tested canine vaccines. They will appear highly effective as long as the majority of dogs remain vaccinated. As soon as a nonvaccinated dog population is large enough to allow virulent agents to spread, disease outbreaks will occur and we will be back where we began 40 years ago.

  20. Histopathologic studies of ischemic optic neuropathy.

    PubMed Central

    Knox, D L; Kerrison, J B; Green, W R

    2000-01-01

    PURPOSE: To define the histopathologic features of eyes in which a pathologic diagnosis of ischemic optic neuropathy had been made in the years 1951 through 1998. METHODS: The following data were documented: age of patient, race, sex, source of tissue, cause of death, clinical history, interval from loss of vision to death, enucleation, exenteration, and biopsy. The histopathologic criteria for diagnosis of ischemic optic neuropathy were the presence of localized ischemic edema, cavernous degeneration, or an area of atrophy located superior or inferior in the optic nerve. Cases with history of abrupt loss of vision were combined with reports from the literature to construct a time table of histopathologic features and associated conditions. RESULTS: Ischemic optic neuropathy was present in 193 eyes. There were 88 females and 65 males. The average age was 71.6 years. Ischemic edema without (early) and with (later) gitter macrophages was present in 26 (13.5%). Cavernous degeneration was present in 69 nerves (36%). Mucopolysaccharide (MPS) was present in 37 cavernous lesions 1 month or longer after loss of vision. Cavernous lesions were seen in 3 eyes in which peripapillary retinal nerve fiber layer hemorrhage had been observed prior to death. Atrophic lesions, the most common pattern, were observed in 133 optic nerves (66.8%). More than 1 ischemic lesion was seen in 38 optic nerves (19.7%). Bilateral ischemic lesions were seen in 50 (35.2%) of 142 paired eyes. CONCLUSIONS: Ischemic optic nerve lesions are initially acellular and later show macrophage infiltration. Cavernous lesions with MPS are present 4 weeks or longer after vision loss. The location of MPS posteriorly and along the internal margin suggests that MPS is produced at the edges of lesions. Progressive vision loss in ischemic optic neuropathy may be secondary to compression of intact nerve from ischemic edema and cavernous swelling, or a second ischemic lesion. Images FIGURE 2 FIGURE 3 FIGURE 4 FIGURE 5

  1. [Efficacy of surgical left ventricular restoration for the patients with ischemic cardiomyopathy; comparison with the surgical treatments for ischemic heart failure (STICH) trial].

    PubMed

    Kokaji, Kiyokazu; Kudo, Mikihiko; Yozu, Ryohei

    2011-10-01

    The efficacy of surgical left ventricular restoration (LVR) for the patients with ischemic cardiomyopathy was denied by the surgical treatments for ischemic heart failure (STICH) trial. But the conclusion of the STICH trial is wrong and real message of the STICH trial is as follows. LVR is not effective procedure for the patients with poor left ventricular function and small left ventricular dilatation. In the STICH trial, volume reduction rate of the patients with LVR is too little. Based on the low of Laplace, little volume reduction rate do not contribute the improvement of the ventricular function. In our 33 cases of LVR, the survival rates at 5, 7, and 10 years after LVR were 80%, 76% and 76%. On the other hand, the corresponding cardiac event-free rates were 55%. 44%, and 44%. These discrepancies of the value suggest the importance of both the preoperative strategy and the intensive therapy during the postoperative period. We observed some cases that re-enlarged left ventricle after LVR induced heart failure or ventricular arrhythmia. The timing of operation, left ventricular reconstruction of appropriate size and shape considering the function of residual myocardium has significant effect on prognosis. Postoperative ventricular tachycardia (VT) was the major factor influenced the survival rate. After preoperative or intraoperative three-dimensional electrical mapping by CARTO system to detect focus of VT, endocardiectomy combined with cryoablation at the VT focus is performed and postoperative antiarrhythmic medication is added routinely. If LVR will be performed after appreciation of its concept, indication and method, excellent long term prognosis will be expected.

  2. Canine distemper virus associated proliferation of canine footpad keratinocytes in vitro.

    PubMed

    Engelhardt, P; Wyder, M; Zurbriggen, A; Gröne, A

    2005-04-25

    Infection of canine footpads with canine distemper virus (CDV) can result in so-called hard pad disease characterized by footpad epidermal proliferation and hyperkeratosis. Cultured canine footpad keratinocytes (CFK) were inoculated with a virulent canine distemper virus strain (A75/17-CDV) to study the effects of CDV-infection on keratinocyte proliferation. Infection was analyzed by immunohistochemistry and in situ hybridization for CDV nucleoprotein (N-protein) antigen and mRNA. CDV caused a persistent, non-cytocidal infection with spread from single cells to infection of the confluent cell layer 7 days post infection (p.i.). Absolute cell numbers were significantly higher in infected cultures compared to control cultures from day 4 until day 6 p.i. Infected cultures contained significantly more total DNA on day 5 p.i. compared to controls. Immunohistochemical investigation of proliferation markers Ki67 and BrdU demonstrated a nearly two-fold increase in numbers of positive cells on day 5 p.i. compared to controls. These findings demonstrate that canine distemper virus infection of canine footpad keratinocytes in vitro was associated with proliferation.

  3. Ischemic brain injury in cerebral amyloid angiopathy

    PubMed Central

    van Veluw, Susanne J; Greenberg, Steven M

    2016-01-01

    Cerebral amyloid angiopathy (CAA) is a common form of cerebral small vessel disease and an important risk factor for intracerebral hemorrhage and cognitive impairment. While the majority of research has focused on the hemorrhagic manifestation of CAA, its ischemic manifestations appear to have substantial clinical relevance as well. Findings from imaging and pathologic studies indicate that ischemic lesions are common in CAA, including white-matter hyperintensities, microinfarcts, and microstructural tissue abnormalities as detected with diffusion tensor imaging. Furthermore, imaging markers of ischemic disease show a robust association with cognition, independent of age, hemorrhagic lesions, and traditional vascular risk factors. Widespread ischemic tissue injury may affect cognition by disrupting white-matter connectivity, thereby hampering communication between brain regions. Challenges are to identify imaging markers that are able to capture widespread microvascular lesion burden in vivo and to further unravel the etiology of ischemic tissue injury by linking structural magnetic resonance imaging (MRI) abnormalities to their underlying pathophysiology and histopathology. A better understanding of the underlying mechanisms of ischemic brain injury in CAA will be a key step toward new interventions to improve long-term cognitive outcomes for patients with CAA. PMID:25944592

  4. [Ocular ischemic syndrome--a case report].

    PubMed

    Zemba, M; Avram, Corina Ioana; Ochinciuc, Uliana; Stamate, Alina Cristina; Camburu, Raluca Lăcrămioara

    2013-01-01

    Ocular ischemic syndrome, also known as hypoperfusion/ hypotensive retinopathy or as ischemic oculopathy is a rare ocular disease determined by chronic arterial hypoperfusion through central retinal artery, posterior and anterior ciliary arteries. It is bilateral in 20% of the cases. Most often it appears due to severe occlusion of the carotid arteries (ICA, MCA>ECA), described in 1963 by Kearns and Hollenhorst. Occasionally it can be determined by the obstruction of ophtalmic artery or some arterities (Takayasu, giant cell arteritis). The risk factors are: age between 50-80 years, males (M:F = 2:1), arterial hypertension, diabetes, coronary diseases (5% of the cases develop ocular ischemic syndrome), vascular stroke, hemodialysis. The case we present is of an 63 years old man known with primary arterial hypertension, hypercholesterolemia, diabetes type 2 non insulin dependent and diagnosticated with ischemic cerebral stroke and bilateral obstruction of internal carotid arteries in march 2010, who is presenting for visual impairment in both eyes. The imaging investigations show important carotid occlusion and at the ophthalmologic evaluation there are ocular hypertension and rubeosis iridis at the right eye, optic atrophy at both eyes (complete in the right eye and partial in the left eye), with superior altitudinal visual field defect in left eye. The following diagnosis was established: Chronic ocular ischemic syndrome in both eyes with Neovascular glaucoma at the right eye, Anterior ischemic optic neuropathy at the left eye and laser panphotocoagulation at the right eye was started.

  5. Reduced expression of CRHR2 and Sp-1 in myocardium of ovariectomized rats is improved by exercise training.

    PubMed

    Tang, Zhiping; Wang, Yujun; Zhu, Xiaoyan; Ni, Xin; Cong, Binhai; Lu, Jianqiang

    2015-01-01

    Exercise training has been looked on as a non-pharmacologic approach to treating ovariectomy (OVX)-induced dysfunctions. In this study, we investigated whether chronic exercise impacts on expression of urocortins (UCNs) and corticotropin-releasing hormone receptor type 2 (CRHR2) in myocardium of OVX rats. Bilateral OVX or sham-operation was performed under anesthesia. Both groups were then divided into two subgroups, with or without treadmill training for 8 weeks. It was found that OVX as well as exercise did not affect the mRNA levels of UCN, UCN2 and UCN3 in myocardium. OVX caused down-regulation of CRHR2 in myocardium. Exercise training reversed the OVX-induced reduction of CRHR2, but had no influence on CRHR2 level in sham rats. OVX resulted in a decrease in estrogen receptor α (ERα) expression in myocardium, which was restored by exercise. Moreover, exercise training also reversed OVX-induced down-regulation of specific protein-1 (Sp-1) expression in myocardium. CRHR2 expression level correlated with Sp-1 and ERα level in myocardium. These results indicate that exercise training can restore the CRHR2 level in myocardium of OVX rats, which is associated with ERα and Sp-1 expression.

  6. Experimental Forelimb Allotransplantation in Canine Model

    PubMed Central

    2016-01-01

    As reconstructive transplantation is gaining popularity as a viable alternative for upper limb amputees, it is becoming increasingly important for plastic surgeons to renew surgical skills and knowledge of this area. Forelimb allotransplantation research has been performed previously in rodent and swine models. However, preclinical canine forelimb allotransplantation studies are lacking in the literature. The purpose of this paper is to provide an overview of the surgical skills necessary to successfully perform forelimb transplantation in canines as a means to prepare for clinical application. A total of 18 transplantation operations on canines were performed. The recipient limb was shortened at the one-third proximal forearm level. The operation was performed in the following order: bones (two reconstructive plates), muscles and tendons (separately sutured), nerves (median, ulnar, and radial nerve), arteries (two), and veins (two). The total mean time of transplantation was 5 hours ± 30 minutes. All of the animals that received transplantation were treated with FK-506 (tacrolimus, 2 mg/kg) for 7 days after surgery. Most allografts survived with perfect viability without vascular problems during the early postoperative period. The canine forelimb allotransplantation model is well qualified to be a suitable training model for standard transplantation and future research work. PMID:27597952

  7. Immune-mediated canine and feline keratitis.

    PubMed

    Andrew, Stacy E

    2008-03-01

    Although the normal cornea is devoid of vasculature and lymphatics, there are still several immune-mediated corneal conditions that can occur in dogs and cats. An overview of corneal immunology is presented. Diseases of dogs, including chronic superficial keratitis, superficial punctate keratitis, and canine adenovirus endotheliitis, as well as feline diseases, including eosinophilic keratitis and herpesvirus-related conditions, are discussed.

  8. Canine distemper outbreak in rhesus monkeys, China.

    PubMed

    Qiu, Wei; Zheng, Ying; Zhang, Shoufeng; Fan, Quanshui; Liu, Hua; Zhang, Fuqiang; Wang, Wei; Liao, Guoyang; Hu, Rongliang

    2011-08-01

    Since 2006, canine distemper outbreaks have occurred in rhesus monkeys at a breeding farm in Guangxi, People's Republic of China. Approximately 10,000 animals were infected (25%-60% disease incidence); 5%-30% of infected animals died. The epidemic was controlled by vaccination. Amino acid sequence analysis of the virus indicated a unique strain.

  9. Seroprevalence of Canine Distemper Virus in Cats

    PubMed Central

    Ikeda, Yasuhiro; Nakamura, Kazuya; Miyazawa, Takayuki; Chen, Ming-Chu; Kuo, Tzong-Fu; Lin, James A.; Mikami, Takeshi; Kai, Chieko; Takahashi, Eiji

    2001-01-01

    A seroepidemiological survey of canine distemper virus (CDV) infection in Asian felids revealed that the prevalence of antibodies varied depending on region and, in some cases, exposure to dogs. The serologic pattern in cats with antibodies indicated that they had likely been exposed to field strains rather than typical CDV vaccine strains. PMID:11329473

  10. Prostate histotripsy for BPH: initial canine results

    NASA Astrophysics Data System (ADS)

    Roberts, William W.; Hall, Timothy L.; Hempel, Christopher R.; Cain, Charles A.

    2009-02-01

    Histotripsy is an extracorporeal ablative technology that utilizes microsecond pulses of intense ultrasound (< 1% duty cycle) to produce nonthermal, mechanical fractionation of targeted tissue. We have previously demonstrated the feasibility of histotripsy prostate ablation. In this study we sought to assess the chronic tissue response, tolerability and safety of histotripsy in a chronic in vivo canine model. Five acute and thirteen chronic canine subjects were anesthetized and treated with histotripsy targeting the prostate. Pulses consisted of 3 cycle bursts of 750 kHz ultrasound at a repetition rate of 300 Hz delivered transabdominally from a highly focused 15 cm aperture array. Transrectal ultrasound imaging provided accurate targeting and real-time monitoring of histotripsy treatment. Prostates were harvested at 0, 7, 28, or 56 days after treatment. Consistent mechanical tissue fractionation and debulking of prostate tissue was seen acutely and at delayed time points without collateral injury. Urothelialization of the treatment cavity was apparent 28 days after treatment. Canine subjects tolerated histotripsy with minimal hematuria or discomfort. Only mild transient lab abnormalities were noted. Histotripsy is a promising non-invasive therapy for prostate tissue fractionation and debulking that appears safe and well tolerated without systemic side effects in the canine model.

  11. [Catecholamines and their metabolic enzymes in the rat myocardium after a flight on the Kosmos-936 biosatellite].

    PubMed

    Kwetncanski, R; Tigranian, R A; Torda, T

    1982-01-01

    In the myocardium of the weightless and centrifuged rats flown for 18.5 days onboard the biosatellite Cosmos-936 the catecholamine concentration and activity of enzymes involved in their synthesis and degradation--dopamine-beta-hydroxylase, monoamine oxidase and catechol-O-methyl transferase--were measured. The catecholamine concentration in the myocardium of both flight groups significantly increased, and the enzyme activity did not change. These results suggest that an exposure to space flight increases the catecholamine concentration and exerts no effect on their synthesis and degradation in the rat myocardium.

  12. Exenatide exerts a PKA-dependent positive inotropic effect in human atrial myocardium: GLP-1R mediated effects in human myocardium.

    PubMed

    Wallner, Markus; Kolesnik, Ewald; Ablasser, Klemens; Khafaga, Mounir; Wakula, Paulina; Ljubojevic, Senka; Thon-Gutschi, Eva Maria; Sourij, Harald; Kapl, Martin; Edmunds, Nicholas J; Kuzmiski, J Brent; Griffith, David A; Knez, Igor; Pieske, Burkert; von Lewinski, Dirk

    2015-12-01

    Glucagon-like peptide-1 receptor (GLP-1R) agonists are a rapidly growing class of drugs developed for treating type-2 diabetes mellitus. Patients with diabetes carry an up to 5-fold greater mortality risk compared to non-diabetic patients, mainly as a result of cardiovascular diseases. Although beneficial cardiovascular effects have been reported, exact mechanisms of GLP-1R-agonist action in the heart, especially in human myocardium, are poorly understood. The effects of GLP-1R-agonists (exenatide, GLP-1(7-36)NH2, PF-06446009, PF-06446667) on cardiac contractility were tested in non-failing atrial and ventricular trabeculae from 72 patients. The GLP-1(7-36)NH2 metabolite, GLP-1(9-36)NH2, was also examined. In electrically stimulated trabeculae, the effects of compounds on isometric force were measured in the absence and presence of pharmacological inhibitors of signal transduction pathways. The role of β-arrestin signaling was examined using a β-arrestin partial agonist, PF-06446667. Expression levels were tested by immunoblots. Translocation of GLP-1R downstream molecular targets, Epac2, GLUT-1 and GLUT-4, were assessed by fluorescence microscopy. All tested GLP-1R-agonists significantly increased developed force in human atrial trabeculae, whereas GLP-1(9-36)NH2 had no effect. Exendin(9-39)NH2, a GLP-1R-antagonist, and H-89 blunted the inotropic effect of exenatide. In addition, exenatide increased PKA-dependent phosphorylation of phospholamban (PLB), GLUT-1 and Epac2 translocation, but not GLUT-4 translocation. Exenatide failed to enhance contractility in ventricular myocardium. Quantitative real-time PCR (qRT-PCR) revealed a significant higher GLP-1R expression in the atrium compared to ventricle. Exenatide increased contractility in a dose-dependent manner via GLP-1R/cAMP/PKA pathway and induced GLUT-1 and Epac2 translocation in human atrial myocardium, but had no effect in ventricular myocardium. Therapeutic use of GLP-1R-agonists may therefore impart

  13. Intrasexual competition and canine dimorphism in anthropoid primates.

    PubMed

    Plavcan, J M; van Schaik, C P

    1992-04-01

    A number of factors, including sexual selection, body weight, body-weight dimorphism, predation, diet, and phylogenetic inertia have been proposed as influences on the evolution of canine dimorphism in anthropoid primates. Although these factors are not mutually exclusive, opinions vary as to which is the most important. The role of sexual selection has been questioned because mating system, which should reflect its strength, poorly predicts variation in canine dimorphism, particularly among polygynous species. Kay et al. (1988) demonstrate that a more refined estimate of intermale competition explains a large proportion of the variation in canine dimorphism in platyrrhine primates. We expand their analysis, developing a more generalized measure of intermale competition based on the frequency and intensity of male-male agonism. We examine the relative influences of predation (inferred by substrate use), female body weight, body-weight dimorphism, diet, and sexual selection on the evolution of anthropoid canine dimorphism. Intermale competition is very strongly associated with canine dimorphism. Predation also has a marked effect on canine dimorphism, in that savanna-dwelling species consistently show greater canine dimorphism than other species, all other factors being held equal. Body-weight dimorphism is also strongly associated with canine dimorphism, though apparently through a common selective basis, rather than through allometric effects. Body weight seems to play only a minor, indirect role in the evolution of canine dimorphism. Diet plays no role. Likewise, we find little evidence that phylogenetic inertia is a constraint on the evolution of canine dimorphism.

  14. Mandibular canine dimensions as an aid in gender estimation

    PubMed Central

    Rajarathnam, Basetty Neelakantam; David, Maria Priscilla; Indira, Annamalai Ponnuswamy

    2016-01-01

    Background: All humans have an identity in life; compassionate societies require this identity to be recognized even after death. Objectives: To measure the dimensions of the mandibular canine and assess the usefulness of the mandibular canine as an aid in gender estimation. Materials and Methods: The study population comprised 200 subjects inclusive of 100 males and 100 females with an age range of 18–25 years. Measurements made in mm at the contact point were of mesiodistal width of the right and left canines and intercanine distance both intraorally and on casts, and the mandibular canine index (MCI) was calculated. The obtained data were subjected to t-test/Mann-Whitney test and discriminant function analysis. Results: All parameters of mandibular canines, namely, intercanine distance, canine width, and canine index were greater in males compared to females suggesting significant sexual dimorphism of mandibular canines. On subjecting the data to discriminant function analysis, it classified sex correctly in 73% of the samples. Conclusion: The result of our study establishes the existence of significant sexual dimorphism in mandibular canines. We can therefore, recommend the use of mandibular canine dimensions as an applicable and additional method for gender determination in human identification. PMID:27555724

  15. Deciduous canine and permanent lateral incisor differential root resorption.

    PubMed

    Davies, K R; Schneider, G B; Southard, T E; Hillis, S L; Wertz, P W; Finkelstein, M; Hogan, M M

    2001-10-01

    When a permanent maxillary canine erupts apical to the permanent lateral incisor and the deciduous canine, resorption typically takes place only on the deciduous canine root. An understanding of this differential resorption could provide insight into the reasons for excessive iatrogenic root resorption during orthodontic tooth movement. The purpose of the present study was to examine the response of roots of permanent lateral incisors and deciduous canines to simulated resorption, and to acid and enzyme attack, reflecting the physiologic environment of an erupting permanent canine. Groups of maxillary permanent lateral incisor and deciduous canine roots were exposed to 5 combinations of Ten Cate demineralizing solution, Ten Cate demineralizing solution with EDTA, and a Type I collagenase solution. Sections of the roots were examined under a polarized light microscope. Analysis of variation of the resulting root lesions demonstrated that the lesion depths for deciduous canines were greater than those for permanent lateral incisors when averaged across 4 of the conditions (F(1,24) = 7.49, P =.0115). On average, deciduous canine roots demonstrated lesions 10% deeper than did permanent lateral incisor roots. We concluded that when deciduous canine and permanent lateral incisor roots are subjected to acid and enzyme attack, reflecting the physiologic environment of an erupting permanent canine, significantly deeper demineralized lesions are seen in the deciduous roots compared with the permanent roots. This finding may partially explain the differential root resorption during permanent tooth eruption.

  16. Quantification of Shear Deformations and Corresponding Stresses in the Biaxially Tested Human Myocardium.

    PubMed

    Sommer, Gerhard; Haspinger, Daniel Ch; Andrä, Michaela; Sacherer, Michael; Viertler, Christian; Regitnig, Peter; Holzapfel, Gerhard A

    2015-10-01

    One goal of cardiac research is to perform numerical simulations to describe/reproduce the mechanoelectrical function of the human myocardium in health and disease. Such simulations are based on a complex combination of mathematical models describing the passive mechanical behavior of the myocardium and its electrophysiology, i.e., the activation of cardiac muscle cells. The problem in developing adequate constitutive models is the shortage of experimental data suitable for detailed parameter estimation in specific functional forms. A combination of shear and biaxial extension tests with different loading protocols on different specimen orientations is necessary to capture adequately the direction-dependent (orthotropic) response of the myocardium. In most experimental animal studies, where planar biaxial extension tests on the myocardium have been conducted, the generated shear stresses were neither considered nor discussed. Hence, in this study a method is presented which allows the quantification of shear deformations and related stresses. It demonstrates an approach for experimenters as to how the generation of these shear stresses can be minimized during mechanical testing. Experimental results on 14 passive human myocardial specimens, obtained from nine human hearts, show the efficiency of this newly developed method. Moreover, the influence of the clamping technique of the specimen, i.e., the load transmission between the testing device and the tissue, on the stress response is determined by testing an isotropic material (Latex). We identified that the force transmission between the testing device and the specimen by means of hooks and cords does not influence the performed experiments. We further showed that in-plane shear stresses definitely exist in biaxially tested human ventricular myocardium, but can be reduced to a minimum by preparing the specimens in an appropriate manner. Moreover, we showed whether shear stresses can be neglected when performing

  17. Radionuclide imaging in ischemic stroke.

    PubMed

    Heiss, Wolf-Dieter

    2014-11-01

    Ischemic stroke is caused by interruption or significant impairment of blood supply to the brain, which leads to a cascade of metabolic and molecular alterations resulting in functional disturbance and morphologic damage. The changes in regional cerebral blood flow and regional metabolism can be assessed by radionuclide imaging, especially SPECT and PET. SPECT and PET have broadened our understanding of flow and metabolic thresholds critical for maintenance of brain function and morphology: PET was essential in the transfer of the concept of the penumbra to clinical stroke and thereby had a great impact on developing treatment strategies. Receptor ligands can be applied as early markers of irreversible neuronal damage and can predict the size of the final infarcts, which is important for decisions on invasive therapy in large ("malignant") infarction. With SPECT and PET, the reserve capacity of the blood supply can be tested in obstructive arteriosclerosis, which is essential for planning interventions. The effect of a stroke on surrounding and contralateral primarily unaffected tissue can be investigated, helping to understand symptoms caused by disturbance in functional networks. Activation studies are useful to demonstrate alternative pathways to compensate for lesions and to test the effect of rehabilitative therapy. Radioisotope studies help to detect neuroinflammation and its effect on extension of tissue damage. Despite the limitations of broad clinical application of radionuclide imaging, this technology has a great impact on research in cerebrovascular diseases and still has various applications in the management of stroke.

  18. Study of retinal vessel oxygen saturation in ischemic and non-ischemic branch retinal vein occlusion

    PubMed Central

    Lin, Lei-Lei; Dong, Yan-Min; Zong, Yao; Zheng, Qi-Shan; Fu, Yue; Yuan, Yong-Guang; Huang, Xia; Qian, Garrett; Gao, Qian-Ying

    2016-01-01

    AIM To explore how oxygen saturation in retinal blood vessels is altered in ischemic and non-ischemic branch retinal vein occlusion (BRVO). METHODS Fifty BRVO eyes were divided into ischemic (n=26) and non-ischemic (n=24) groups, based on fundus fluorescein angiography. Healthy individuals (n=52 and n=48, respectively) were also recruited as controls for the two groups. The mean oxygen saturations of the occluded vessels and central vessels were measured by oximetry in the BRVO and control groups. RESULTS In the ischemic BRVO group, the occluded arterioles oxygen saturation (SaO2-A, 106.0%±14.3%), instead of the occluded venule oxygen saturation (SaO2-V, 60.8%±9.4%), showed increases when compared with those in the same quadrant vessels (SaO2-A, 86.1%±16.5%) in the contralateral eyes (P<0.05). The oxygen saturations of the central vessels showed similar trends with those of the occluded vessels. In the non-ischemic BRVO group, the occluded and central SaO2-V and SaO2-A showed no significant changes. In both the ischemic and non-ischemic BRVOs, the central SaO2-A was significantly increased when compared to healthy individuals. CONCLUSION Obvious changes in the occluded and central SaO2-A were found in the ischemic BRVO group, indicating that disorders of oxygen metabolism in the arterioles may participate in the pathogenesis of ischemic BRVO. PMID:26949618

  19. Survivin expression in canine epidermis and in canine and human cutaneous squamous cell carcinomas.

    PubMed

    Bongiovanni, Laura; Colombi, Isabella; Fortunato, Carmine; Della Salda, Leonardo

    2009-10-01

    Survivin, a member of the inhibitor of apoptosis protein (IAP) family, is ubiquitously expressed during tissue development, undetectable in most normal tissues, but re-expressed in most cancers, including skin malignancies. Expression of survivin was evaluated retrospectively in 19 canine cutaneous squamous cell carcinomas (SCCs; one in situ; 16 well differentiated; one invasive, one lymph node metastasis) and 19 well differentiated SCCs from human beings. Seven specimens of normal canine skin were included. Immunohistochemical expression of full-length survivin was determined using a commercially available antibody. In addition, apoptotic rate [Terminal deoxynucleotidyl Transferase Biotin-dUTP Nick End Labelling index (TUNEL) index] and mitotic index (MI), counting mitoses in 10 high power fields (HPF), were determined. Scattered survivin positive nuclei were identified in the epidermal basal cell layer of normal canine skin. Nuclear survivin expression was identified in 18 of 19 human and in all canine SCCs, mainly along the base of the tumour cell population. Cytoplasmic survivin expression was rarely observed in human SCCs and in 84.2% of canine SCCs. The TUNEL index ranged from 0.1 to 2.6 in human beings and from 7.5 to 69.4 in dogs, while MIs ranged from 0 to 4 in human beings and dogs. No correlation was found between survivin expression and apoptotic or mitotic rates. Canine and human tumours showed similar nuclear survivin expression, indicating similar functions of the molecule. We demonstrated survivin expression in normal adult canine epidermis. Increased nuclear survivin expression in pre-neoplastic and neoplastic lesions demonstrates a possible association of survivin with development of SCCs in human beings and dogs.

  20. [A simple kinetic model of myocardium contraction: calcium-mechanics coupling].

    PubMed

    Semin, F A

    2014-01-01

    A kinetic model of cardiac muscle contraction is suggested. It is based on our earlier simplified model of the kinetics of the actin-myosin interaction. We examined the kinetics of formation of calcium-troponin complexes that open the binding sites-on actin for myosin heads. The model also takes into account the cooperativity of this process and the influence of myosin heads on it. It was shown that with proper choice of its parameters the model appropriately describes the dependence of myocardium activation.on sarcomeres length that underlies the Frank-Starling law of the heart. The model fits both steady state experiments on myocardial specimens with permeable membrane and twitch contractions of intact cardiac muscle. It also describes well the myocardium load-dependent relaxation.

  1. Remodeling of myocardium in rat with chronic dyslipidemia and under conditions of verapamil treatment.

    PubMed

    Klinnikova, M G; Yuzhik, E I; Pichigin, V I; Lushnikova, E L

    2014-11-01

    The type and intensity of remodeling (structural reorganization) of the myocardium in Wistar rats were studied under conditions of experimental chronic dyslipidemia and verapamil treatment. Long (64 days) atherogenic diet caused dyslipidemia and led to reduction of the heart percent weight. The cytopathic effect of dyslipidemia manifested in more intense lytic injuries of cardiomyocytes, development of diffuse and small focal cardiosclerosis under conditions of manifest circulatory disorders. Remodeling of the myocardium during various periods of the experiment manifested in a higher connective tissue/cardiomyocyte volume ratio (by 74% after 30 days and by 58-62% after 64 days of experiment). Verapamil injection promoted attenuation of lytic changes in cardiomyocytes and in fibroplastic reactions of the stroma, but failed to prevent them completely.

  2. Myoblasts transplanted into rat infarcted myocardium are functionally isolated from their host

    PubMed Central

    Léobon, Bertrand; Garcin, Isabelle; Menasché, Philippe; Vilquin, Jean-Thomas; Audinat, Etienne; Charpak, Serge

    2003-01-01

    Survival and differentiation of myogenic cells grafted into infarcted myocardium have raised the hope that cell transplantation becomes a new therapy for cardiovascular diseases. The approach was further supported by transplantation of skeletal myoblasts, which was shown to improve cardiac performance in several animal species. Despite the success of myoblast transplantation and its recent trial in human, the mechanism responsible for the functional improvement remains unclear. Here, we used intracellular recordings coupled to video and fluorescence microscopy to establish whether myoblasts, genetically labeled with enhanced GFP and transplanted into rat infarcted myocardium, retain excitable and contractile properties, and participate actively to cardiac function. Our results indicate that grafted myoblasts differentiate into peculiar hyperexcitable myotubes with a contractile activity fully independent of neighboring cardiomyocytes. We conclude that mechanisms other than electromechanical coupling between grafted and host cells are involved in the improvement of cardiac function. PMID:12805561

  3. Enhanced infarct myocardium repair mediated by thermosensitive copolymer hydrogel-based stem cell transplantation

    PubMed Central

    Xia, Yu; Zhu, Kai; Lai, Hao; Lang, Meidong; Xiao, Yan; Lian, Sheng

    2015-01-01

    Mesenchymal stem cell (MSC) transplantation by intramyocardial injection has been proposed as a promising therapy strategy for cardiac repair after myocardium infarction. However, low retention and survival of grafted MSCs hinder its further application. In this study, copolymer with N-isopropylacrylamide/acrylic acid/2-hydroxylethyl methacrylate-poly(ɛ-caprolactone) ratio of 88:9.6:2.4 was bioconjugated with type I collagen to construct a novel injectable thermosensitive hydrogel. The injectable and biocompatible hydrogel-mediated MSC transplantation could enhance the grafted cell survival in the myocardium, which contributed to the increased neovascularization, decreased interstitial fibrosis, and ultimately improved heart function to a significantly greater degree than regular MSC transplantation. We suggest that this novel hydrogel has the potential for future stem cell transplantation. PMID:25432986

  4. Enhanced infarct myocardium repair mediated by thermosensitive copolymer hydrogel-based stem cell transplantation.

    PubMed

    Xia, Yu; Zhu, Kai; Lai, Hao; Lang, Meidong; Xiao, Yan; Lian, Sheng; Guo, Changfa; Wang, Chunsheng

    2015-05-01

    Mesenchymal stem cell (MSC) transplantation by intramyocardial injection has been proposed as a promising therapy strategy for cardiac repair after myocardium infarction. However, low retention and survival of grafted MSCs hinder its further application. In this study, copolymer with N-isopropylacrylamide/acrylic acid/2-hydroxylethyl methacrylate-poly(ɛ-caprolactone) ratio of 88:9.6:2.4 was bioconjugated with type I collagen to construct a novel injectable thermosensitive hydrogel. The injectable and biocompatible hydrogel-mediated MSC transplantation could enhance the grafted cell survival in the myocardium, which contributed to the increased neovascularization, decreased interstitial fibrosis, and ultimately improved heart function to a significantly greater degree than regular MSC transplantation. We suggest that this novel hydrogel has the potential for future stem cell transplantation.

  5. Second harmonic generation imaging of the collagen in myocardium for atrial fibrillation diagnosis

    NASA Astrophysics Data System (ADS)

    Tsai, Ming-Rung; Chiou, Yu-We; Sun, Chi-Kuang

    2009-02-01

    Myocardial fibrosis, a common sequela of cardiac hypertrophy, has been shown to be associated with arrhythmias in experimental models. Some research has indicated that myocardial fibrosis plays an important role in predisposing patients to atrial fibrillation. Second harmonic generation (SHG) is an optically nonlinear coherent process to image the collagen network. In this presentation, we observe the SHG images of the collagen matrix in atrial myocardium and we analyzed of collagen fibers arrangement by using Fourier-transform analysis. Moreover, comparing the SHG images of the collagen fibers in atrial myocardium between normal sinus rhythm (NSR) and atrial fibrillation (AF), our result indicated that it is possible to realize the relation between myocardial fibrosis and AF.

  6. Mathematical modeling of mechanically modulated rhythm disturbances in homogeneous and heterogeneous myocardium with attenuated activity of na+ -k+ pump.

    PubMed

    Sulman, Tatiana; Katsnelson, Leonid B; Solovyova, Olga; Markhasin, Vladimir S

    2008-04-01

    A mathematical model of the cardiomyocyte electromechanical function is used to study contribution of mechanical factors to rhythm disturbances in the case of the cardiomyocyte calcium overload. Particular attention is paid to the overload caused by diminished activity of the sodium-potassium pump. It is shown in the framework of the model, where mechano-calcium feedback is accounted for that myocardium mechanics may significantly enhance arrhythmogenicity of the calcium overload. Specifically, a role of cross-bridge attachment/detachment processes, a role of mechanical conditions of myocardium contractions (length, load), and a role of myocardium viscosity in the case of simulated calcium overload have been revealed. Underlying mechanisms are analyzed. Several approaches are designed in the model and compared to each other for recovery of the valid myocardium electrical and mechanical performance in the case of the partially suppressed sodium-potassium pump.

  7. Imaging necrotic myocardium: Detection with 99mTc-pyrophosphate and radiolabeled antimyosin

    SciTech Connect

    Khaw, B.A.; Haber, E. )

    1989-08-01

    The major value of hot-spot imaging of the myocardium is its ability to define areas of necrosis rather than areas of diminished blood flow or cellular function. Applications of hot-spot imaging include the diagnosis and quantitation of myocardial infarction, myocarditis, and cardiac transplant rejection. The two agents in clinical use, 99mTc-Pyrophosphate and radiolabeled antimyosin, are discussed. 52 references.

  8. Regulation of acetylation restores proteolytic function of diseased myocardium in mouse and human.

    PubMed

    Wang, Ding; Fang, Caiyun; Zong, Nobel C; Liem, David A; Cadeiras, Martin; Scruggs, Sarah B; Yu, Hongxiu; Kim, Allen K; Yang, Pengyuan; Deng, Mario; Lu, Haojie; Ping, Peipei

    2013-12-01

    Proteasome complexes play essential roles in maintaining cellular protein homeostasis and serve fundamental roles in cardiac function under normal and pathological conditions. A functional detriment in proteasomal activities has been recognized as a major contributor to the progression of cardiovascular diseases. Therefore, approaches to restore proteolytic function within the setting of the diseased myocardium would be of great clinical significance. In this study, we discovered that the cardiac proteasomal activity could be regulated by acetylation. Histone deacetylase (HDAC) inhibitors (suberoylanilide hydroxamic acid and sodium valproate) enhanced the acetylation of 20S proteasome subunits in the myocardium and led to an elevation of proteolytic capacity. This regulatory paradigm was present in both healthy and acutely ischemia/reperfusion (I/R) injured murine hearts, and HDAC inhibition in vitro restored proteolytic capacities to baseline sham levels in injured hearts. This mechanism of regulation was also viable in failing human myocardium. With 20S proteasomal complexes purified from murine myocardium treated with HDAC inhibitors in vivo, we confirmed that acetylation of 20S subunits directly, at least in part, presents a molecular explanation for the improvement in function. Furthermore, using high-resolution LC-MS/MS, we unraveled the first cardiac 20S acetylome, which identified the acetylation of nine N-termini and seven internal lysine residues. Acetylation on four lysine residues and four N-termini on cardiac proteasomes were novel discoveries of this study. In addition, the acetylation of five lysine residues was inducible via HDAC inhibition, which correlated with the enhancement of 20S proteasomal activity. Taken as a whole, our investigation unveiled a novel mechanism of proteasomal function regulation in vivo and established a new strategy for the potential rescue of compromised proteolytic function in the failing heart using HDAC inhibitors.

  9. Effect of ethanol and the catalase inhibitor aminotriazole on lipid peroxidation in the rat myocardium

    SciTech Connect

    Panchenko, L.F.; Pirozhkov, S.V.; Popova, S.V.; Antonenkov, V.D.

    1987-09-01

    The authors study the effect of chronic administration of ethanol and aminotriazole on the level of lipid peroxidation in the ray myocardium. The action of natural and artificial antioxidants on alcohol-induced lipid peroxidation also was studied. To determine the level of chemiluminescence, 1 ml of a sample of nuclear free homogenate or of the total fraction of particles was introduced for radioactivity measurement. After incubation the spontaneous weak luminescence was measured.

  10. Effects of myocardial infarction on the distribution and transport of nutrients and oxygen in porcine myocardium.

    PubMed

    Davis, Bryce H; Morimoto, Yoshihisa; Sample, Chris; Olbrich, Kevin; Leddy, Holly A; Guilak, Farshid; Taylor, Doris A

    2012-10-01

    One of the primary limitations of cell therapy for myocardial infarction is the low survival of transplanted cells, with a loss of up to 80% of cells within 3 days of delivery. The aims of this study were to investigate the distribution of nutrients and oxygen in infarcted myocardium and to quantify how macromolecular transport properties might affect cell survival. Transmural myocardial infarction was created by controlled cryoablation in pigs. At 30 days post-infarction, oxygen and metabolite levels were measured in the peripheral skeletal muscle, normal myocardium, the infarct border zone, and the infarct interior. The diffusion coefficients of fluorescein or FITC-labeled dextran (0.3-70 kD) were measured in these tissues using fluorescence recovery after photobleaching. The vascular density was measured via endogenous alkaline phosphatase staining. To examine the influence of these infarct conditions on cells therapeutically used in vivo, skeletal myoblast survival and differentiation were studied in vitro under the oxygen and glucose concentrations measured in the infarct tissue. Glucose and oxygen concentrations, along with vascular density were significantly reduced in infarct when compared to the uninjured myocardium and infarct border zone, although the degree of decrease differed. The diffusivity of molecules smaller than 40 kD was significantly higher in infarct center and border zone as compared to uninjured heart. Skeletal myoblast differentiation and survival were decreased stepwise from control to hypoxia, starvation, and ischemia conditions. Although oxygen, glucose, and vascular density were significantly reduced in infarcted myocardium, the rate of macromolecular diffusion was significantly increased, suggesting that diffusive transport may not be inhibited in infarct tissue, and thus the supply of nutrients to transplanted cells may be possible. in vitro studies mimicking infarct conditions suggest that increasing nutrients available to

  11. Myoglobin translational diffusion in rat myocardium and its implication on intracellular oxygen transport

    PubMed Central

    Lin, Ping-Chang; Kreutzer, Ulrike; Jue, Thomas

    2007-01-01

    Current theory of respiratory control invokes a role of myoglobin (Mb)-facilitated O2 diffusion in regulating the intracellular O2 flux, provided Mb diffusion can compete effectively with free O2 diffusion. Pulsed-field gradient NMR methods have now followed gradient-dependent changes in the distinct 1H NMR γ CH3 Val E11 signal of MbO2 in perfused rat myocardium to obtain the endogenous Mb translational diffusion coefficient (DMb) of 4.24 × 10−7 cm2 s−1 at 22°C. The DMb matches precisely the value predicted by in vivo NMR rotational diffusion measurements of Mb and shows no orientation preference. Given values in the literature for the Krogh's free O2 diffusion coefficient (K0), myocardial Mb concentration and a partial pressure of O2 that half saturates Mb (P50), the analysis yields an equipoise diffusion PO2 of 1.77 mmHg, where Mb and free O2 contribute equally to the O2 flux. In the myocardium, Mb-facilitated O2 diffusion contributes increasingly more than free O2 diffusion when the PO2 falls below 1.77 mmHg. In skeletal muscle, the PO2 must fall below 5.72 mmHg. Altering the Mb P50 induces modest change. Mb-facilitated diffusion has a higher poise in skeletal muscle than in myocardium. Because the basal PO2 hovers around 10 mmHg, Mb does not have a predominant role in facilitating O2 transport in myocardium but contributes significantly only when cellular oxygen falls below the equipoise diffusion PO2. PMID:17038435

  12. Influence of mechanical ventilation and sepsis on redox balance in diaphragm, myocardium, limb muscles, and lungs.

    PubMed

    Chacon-Cabrera, Alba; Rojas, Yeny; Martínez-Caro, Leticia; Vila-Ubach, Monica; Nin, Nicolas; Ferruelo, Antonio; Esteban, Andrés; Lorente, José A; Barreiro, Esther

    2014-12-01

    Mechanical ventilation (MV), using high tidal volumes (V(T)), causes lung (ventilator-induced lung injury [VILI]) and distant organ injury. Additionally, sepsis is characterized by increased oxidative stress. We tested whether MV is associated with enhanced oxidative stress in sepsis, the commonest underlying condition in clinical acute lung injury. Protein carbonylation and nitration, antioxidants, and inflammation (immunoblotting) were evaluated in diaphragm, gastrocnemius, soleus, myocardium, and lungs of nonseptic and septic (cecal ligation and puncture 24 hours before MV) rats undergoing MV (n = 7 per group) for 150 minutes using 3 different strategies (low V(T) [V(T) = 9 mL/kg], moderate V(T) [V(T) = 15 mL/kg], and high V(T) [V(T) = 25 mL/kg]) and in nonventilated control animals. Compared with nonventilated control animals, in septic and nonseptic rodents (1) diaphragms, limb muscles, and myocardium of high-V(T) rats exhibited a decrease in protein oxidation and nitration levels, (2) antioxidant levels followed a specific fiber-type distribution in slow- and fast-twitch muscles, (3) tumor necrosis factor α (TNF-α) levels were higher in respiratory and limb muscles, whereas no differences were observed in myocardium, and (4) in lungs, protein oxidation was increased, antioxidants were rather decreased, and TNF-α remained unmodified. In this model of VILI, oxidative stress does not occur in distant organs or skeletal muscles of rodents after several hours of MV with moderate-to-high V(T), whereas protein oxidation levels were increased in the lungs of the animals. Inflammatory events were moderately expressed in skeletal muscles and lungs of the MV rats. Concomitant sepsis did not strongly affect the MV-induced effects on muscles, myocardium, or lungs in the rodents.

  13. Effect of hyperbaric oxygenation on carbohydrate metabolism protein synthesis in the myocardium during sustained hypodynamia

    NASA Technical Reports Server (NTRS)

    Makarov, G. A.

    1980-01-01

    Glycolysis and the intensity of protein synthesis were studied in 140 white male rats in subcellular fractions of the myocardium during 45 day hypodynamia and hyperbaric oxygenation. Hypodynamia increased: (1) the amount of lactic acids; (2) the amount of pyruvic acid; (3) the lactate/pyruvate coefficient; and (4) the activities of aldolase and lactate dehydrogenase. Hyperbaric oxygenation was found to have a favorable metabolic effect on the animals with hypodynamia.

  14. Genetic Predisposition to Ischemic Stroke

    PubMed Central

    Kamatani, Yoichiro; Takahashi, Atsushi; Hata, Jun; Furukawa, Ryohei; Shiwa, Yuh; Yamaji, Taiki; Hara, Megumi; Tanno, Kozo; Ohmomo, Hideki; Ono, Kanako; Takashima, Naoyuki; Matsuda, Koichi; Wakai, Kenji; Sawada, Norie; Iwasaki, Motoki; Yamagishi, Kazumasa; Ago, Tetsuro; Ninomiya, Toshiharu; Fukushima, Akimune; Hozawa, Atsushi; Minegishi, Naoko; Satoh, Mamoru; Endo, Ryujin; Sasaki, Makoto; Sakata, Kiyomi; Kobayashi, Seiichiro; Ogasawara, Kuniaki; Nakamura, Motoyuki; Hitomi, Jiro; Kita, Yoshikuni; Tanaka, Keitaro; Iso, Hiroyasu; Kitazono, Takanari; Kubo, Michiaki; Tanaka, Hideo; Tsugane, Shoichiro; Kiyohara, Yutaka; Yamamoto, Masayuki; Sobue, Kenji; Shimizu, Atsushi

    2017-01-01

    Background and Purpose— The prediction of genetic predispositions to ischemic stroke (IS) may allow the identification of individuals at elevated risk and thereby prevent IS in clinical practice. Previously developed weighted multilocus genetic risk scores showed limited predictive ability for IS. Here, we investigated the predictive ability of a newer method, polygenic risk score (polyGRS), based on the idea that a few strong signals, as well as several weaker signals, can be collectively informative to determine IS risk. Methods— We genotyped 13 214 Japanese individuals with IS and 26 470 controls (derivation samples) and generated both multilocus genetic risk scores and polyGRS, using the same derivation data set. The predictive abilities of each scoring system were then assessed using 2 independent sets of Japanese samples (KyushuU and JPJM data sets). Results— In both validation data sets, polyGRS was shown to be significantly associated with IS, but weighted multilocus genetic risk scores was not. Comparing the highest with the lowest polyGRS quintile, the odds ratios for IS were 1.75 (95% confidence interval, 1.33–2.31) and 1.99 (95% confidence interval, 1.19–3.33) in the KyushuU and JPJM samples, respectively. Using the KyushuU samples, the addition of polyGRS to a nongenetic risk model resulted in a significant improvement of the predictive ability (net reclassification improvement=0.151; P<0.001). Conclusions— The polyGRS was shown to be superior to weighted multilocus genetic risk scores as an IS prediction model. Thus, together with the nongenetic risk factors, polyGRS will provide valuable information for individual risk assessment and management of modifiable risk factors. PMID:28034966

  15. Sexual dimorphism in canine shape among extant great apes.

    PubMed

    Kelley, J

    1995-04-01

    There have been numerous attempts to sex fossil specimens using the canine dentition. Whether focused on canine size or canine shape, most of these efforts share two deficiencies: lack of quantification of male-female differences in the adopted criteria and a failure to adequately explore among extant species the discriminatory power of these criteria. Here, canine shape indices relating to relative canine height, upper canine root/crown proportionality, and relative length of the lower canine mesial ridge were calculated for males and females of all species and subspecies of extant great apes and two species of gibbons. The accuracy of these indices for identifying the sex of the extant ape specimens was investigated through discriminant analysis and the use of bivariate plots of the two upper and two lower canine indices. The indices were found to be highly accurate in identifying the sex of great ape individuals, not only in single-species and subspecies samples but in mixed-species samples as well; assignment error rates were mostly between 0 and 4%. Accuracy was lowest in Pan (error rates as high as 15%) and highest in Pongo (one error). In most cases, error rates were lower in the upper canines. The effectiveness of these shape indices for sexing might be related to the degree of absolute canine size dimorphism; the indices did not effectively segregate males and females among minimally canine-dimorphic gibbons. The mixed-species results reveal that same-sex index values are remarkably concordant across great ape species, as are the patterns of spatial segregation of males and females in the bivariate plots. Results suggest that, while the indices can be used with some confidence to sex individual fossil specimens, their greatest utility will be for identifying the sex of groups of canines united by size and morphology.

  16. Unilateral Maxillary Canine Agenesis: A Case Report and Literature Review

    PubMed Central

    Koç, Nagihan; Çağırankaya, L. Berna; Akkaya, Nursel

    2014-01-01

    Congenital absence of maxillary permanent canines is an extremely rare condition, which may appear as part of a syndrome or as a nonsyndromic form. Nonsyndromic canine agenesis combined with other types of tooth agenesis has occasionally been described in the literature but isolated cases are rarely observed. This report presents an isolated case of maxillary permanent canine agenesis in a healthy 18-year-old female patient and a literature review on the prevalence, etiology, and differential diagnosis of the condition. PMID:25177502

  17. Expression of Bax Protein and Morphological Changes in the Myocardium in Experimental Acute Pressure Overload of the Left Ventricle.

    PubMed

    Blagonravov, M L; Korshunova, A Yu; Azova, M M; Bryk, A A; Frolov, V A

    2016-06-01

    The expression of Bax protein, marker of intracellular pathway of apoptosis initiation, in viable left ventricular cardiomyocytes and morphological changes in the myocardium in acute pressure overload of the left ventricle were studied in experiment on male rabbits. The content of Bax protein in the cardiomyocyte cytoplasm decreased, this indicating that the mitochondrial pathway was not involved in the realization of the apoptotic program. This decrease was associated with manifest destructive changes in the left ventricular myocardium.

  18. Interstitial pneumonia in neonatal canine pups with evidence of canine distemper virus infection.

    PubMed

    Pandher, Karamjeet; Podell, Brendan; Gould, Daniel H; Johnson, Bill J; Thompson, Sheri

    2006-03-01

    Four dead canine pups (5-12 days old) from 3 litters in Douglas County of north central Colorado were submitted to the Colorado State University Diagnostic Laboratory for necropsy. Pups were originally presented to the referring clinics for respiratory tract illness, with or without diarrhea. At necropsy, the lungs from all pups had similar lesions, including random foci of hemorrhage and failure to collapse on opening of the thoracic cavity. The lungs were histologically characterized by subacute interstitial pneumonia, with alveolar septa expanded by a histiocyte-rich infiltrate with a few lymphocytes and neutrophils. The alveolar spaces were filled with moderate amounts of proteinaceous fluid, foamy macrophages, and a few neutrophils. Lungs from 3 of the 4 pups were test positive for canine distemper virus (CDV) by use of reverse transcriptase-polymerase chain reaction (RT-PCR) analysis. Immunohistochemically stained lungs, including those from the pup that were CDV negative, by use of RT-PCR analysis, were test positive for CDV antigen in bronchial and bronchiolar epithelial cells and in a few alveolar macrophages. Central nervous system lesions were not observed in any of the 4 pups. These cases represent an unusual presentation of canine distemper in neonatal pups marked by respiratory tract lesions without central nervous system involvement. Canine distemper should be considered in the differential diagnosis of neonatal canine respiratory tract illness.

  19. Redundancy and evolution of GATA factor requirements in development of the myocardium.

    PubMed

    Peterkin, Tessa; Gibson, Abigail; Patient, Roger

    2007-11-15

    The transcription factors, GATA4, 5 and 6, recognize the same DNA sequence and are all expressed in the developing myocardium. However, knockout studies in the mouse have indicated that none of them are absolutely required for the specification of the myocardium. Here we present evidence for redundancy in this family for the first time. Using morpholinos in both Xenopus and zebrafish embryos, we show that GATA4 knockdown, for example, only affects cardiac marker expression in the absence of either GATA5 or GATA6. A similar situation pertains for GATA5 in Xenopus whereas, in zebrafish, GATA5 (faust) plays a major role in driving the myocardial programme. This requirement for GATA5 in zebrafish is for induction of the myocardium, in contrast to the GATA6 requirement in both species, which is for differentiation. This early role for GATA5 in zebrafish correlates with its earlier expression and with an earlier requirement for BMP signalling, suggesting that a mutual maintenance loop for GATA, BMP and Nkx expression is the evolutionarily conserved entity.

  20. Anisotropy of the transverse mode ultrasonic properties of fixed tendon and fixed myocardium.

    PubMed

    Hoffmeister, B K; Gehr, S E; Miller, J G

    1996-06-01

    This study investigates the influence of the fiber-reinforced nature of myocardium and tendon on the propagation of transverse mode ultrasonic waves. Formalin fixed specimens of normal human left ventricular cardiac muscle and bovine Achilles tendon were prepared for this study in such a way that transverse mode ultrasonic waves could be propagated perpendicular to the fiber axis of the tissue with the polarization oriented either parallel or perpendicular to the fiber axis. Measurements of velocity and attenuation were made at 3 MHz to assess the degree of anisotropy in these parameters for both tissues. Formalin fixed tendon exhibited a significant anisotropy whereas formalin fixed myocardium displayed a similar trend of more modest magnitude. Results of these measurements were used to compute two elastic stiffness coefficients for each tissue, yielding c44 = 37.2 MPa and c66 = 18.0 MPa for formalin fixed tendon, and c44 = 8.97 MPa and c66 = 8.45 MPa for formalin fixed myocardium. To validate this approach, additional studies were conducted to measure the transverse mode ultrasonic properties of silicone rubber and motor oil.

  1. The endoderm and myocardium join forces to drive early heart tube assembly.

    PubMed

    Aleksandrova, Anastasiia; Czirok, Andras; Kosa, Edina; Galkin, Oleksandr; Cheuvront, Tracey J; Rongish, Brenda J

    2015-08-01

    Formation of the muscular layer of the heart, the myocardium, involves the medial movement of bilateral progenitor fields; driven primarily by shortening of the endoderm during foregut formation. Using a combination of time-lapse imaging, microsurgical perturbations and computational modeling, we show that the speed of the medial-ward movement of the myocardial progenitors is similar, but not identical to that of the adjacent endoderm. Further, the extracellular matrix microenvironment separating the two germ layers also moves with the myocardium, indicating that collective tissue motion and not cell migration drives tubular heart assembly. Importantly, as myocardial cells approach the midline, they perform distinct anterior-directed movements relative to the endoderm. Based on the analysis of microincision experiments and computational models, we propose two characteristic, autonomous morphogenetic activities within the early myocardium: 1) an active contraction of the medial portion of the heart field and 2) curling- the tendency of the unconstrained myocardial tissue to form a spherical surface with a concave ventral side. In the intact embryo, these deformations are constrained by the endoderm and the adjacent mesoderm, nevertheless the corresponding mechanical stresses contribute to the proper positioning of myocardial primordia.

  2. Polarization birefringence measurements for characterizing the myocardium, including healthy, infarcted, and stem-cell-regenerated tissues

    NASA Astrophysics Data System (ADS)

    Wood, Michael F. G.; Ghosh, Nirmalya; Wallenburg, Marika A.; Li, Shu-Hong; Weisel, Richard D.; Wilson, Brian C.; Li, Ren-Ke; Vitkin, I. Alex

    2010-07-01

    Myocardial infarction leads to structural remodeling of the myocardium, in particular to the loss of cardiomyocytes due to necrosis and an increase in collagen with scar formation. Stem cell regenerative treatments have been shown to alter this remodeling process, resulting in improved cardiac function. As healthy myocardial tissue is highly fibrous and anisotropic, it exhibits optical linear birefringence due to the different refractive indices parallel and perpendicular to the fibers. Accordingly, changes in myocardial structure associated with infarction and treatment-induced remodeling will alter the anisotropy exhibited by the tissue. Polarization-based linear birefringence is measured on the myocardium of adult rat hearts after myocardial infarction and compared with hearts that had received mesenchymal stem cell treatment. Both point measurement and imaging data show a decrease in birefringence in the region of infarction, with a partial rebound back toward the healthy values following regenerative treatment with stem cells. These results demonstrate the ability of optical polarimetry to characterize the micro-organizational state of the myocardium via its measured anisotropy, and the potential of this approach for monitoring regenerative treatments of myocardial infarction.

  3. Aspirin upregulates αB-Crystallin to protect the myocardium against heat stress in broiler chickens

    PubMed Central

    Tang, Shu; Yin, Bin; Song, Erbao; Chen, Hongbo; Cheng, Yanfen; Zhang, Xiaohui; Bao, Endong; Hartung, Joerg

    2016-01-01

    We established in vivo and in vitro models to investigate the role of αB-Crystallin (CryAB) and assess the ability of aspirin (ASA) to protect the myocardium during prolonged heat stress. Thirty-day-old chickens were divided into three groups (n = 90): heat stress (HS, 40±1 °C); ASA(−)HS(+), 1 mg/kg ASA orally 2 h before heat stress; and ASA(+)HS(−), pretreated with aspirin, no heat stress (25 °C). Hearts were excised after 0, 1, 2, 3, 5, 7, 10, 15 and 24 h. Heat stress increased body temperature, though the ASA(−)HS(+) group had significantly higher temperatures than the ASA(+)HS(+) group at all time points. Compared to ASA(+)HS(+), the ASA(−)HS(+) group displayed increased sensitivity to heat stress. Pathological analysis revealed the ASA (+)HS(+) myocardium showed less severe changes (narrowed, chaotic fibers; fewer necrotic cells) than the ASA(−)HS(+) group (bleeding and extensive cell death). In vitro, ASA-pretreatment significantly increased primary chicken myocardial cell survival during heat stress. ELISAs indicated ASA induced CryAB in vivo to protect against heat stress-induced myocardial damage, but ASA did not induce CryAB in primary chicken myocardial cells. The mechanisms by which ASA induces the expression of CryAB in vivo and protects the myocardium during heat stress merit further research. PMID:27857180

  4. Macro- and micronutrient dyshomeostasis in the adverse structural remodelling of myocardium

    PubMed Central

    Weber, Karl T.; Weglicki, William B.; Simpson, Robert U.

    2009-01-01

    Hypertension and heart failure are worldwide health problems of ever-increasing proportions. A failure of the heart, during either systolic and/or diastolic phases of the cardiac cycle, has its origins rooted in an adverse structural, biochemical, and molecular remodelling of myocardium that involves its cellular constituents, extracellular matrix, and intramural coronary vasculature. Herein we focus on the pathogenic role of a dyshomeostasis of several macro- (i.e. Ca2+ and Mg2+) and micronutrients (i.e. Zn2+, Se2+, and vitamin D) in contributing to adverse remodelling of the myocardium and its failure as a pulsatile muscular pump. An improved understanding of how these macro- and micronutrients account for the causes and consequences of adverse myocardial remodelling carries with it the potential of identifying new biomarkers predictive of risk, onset and progression, and response to intervention(s), which could be monitored non-invasively and serially over time. Moreover, such incremental knowledge will serve as the underpinning to the development of novel strategies aimed at preventing and/or regressing the ongoing adverse remodelling of myocardium. The time is at hand to recognize the importance of macro- and micronutrient dyshomeostasis in the evaluation and management of hypertension and heart failure. PMID:18835843

  5. Developmental processes and canine dimorphism in primate evolution.

    PubMed

    Schwartz, Gary T; Miller, Ellen R; Gunnell, Gregg F

    2005-01-01

    Understanding the evolutionary history of canine sexual dimorphism is important for interpreting the developmental biology, socioecology and phylogenetic position of primates. All current evidence for extant primates indicates that canine dimorphism is achieved through bimaturism rather than via differences in rates of crown formation time. Using incremental growth lines, we charted the ontogeny of canine formation within species of Eocene Cantius, the earliest known canine-dimorphic primate, to test whether canine dimorphism via bimaturism was developmentally canalized early in primate evolution. Our results show that canine dimorphism in Cantius is achieved primarily through different rates of crown formation in males and females, not bimaturism. This is the first demonstration of rate differences resulting in canine dimorphism in any primate and therefore suggests that canine dimorphism is not developmentally homologous across Primates. The most likely interpretation is that canine dimorphism has been selected for at least twice during the course of primate evolution. The power of this approach is its ability to identify underlying developmental processes behind patterns of morphological similarity, even in long-extinct primate species.

  6. Interceptive approach to treatment of impacted maxillary canines.

    PubMed

    de Mendonça, Marcos Rogério; Verri, Ana Caroline Gonçales; Martins, Lídia Pimenta; Fabre, Aubrey Fernando; Cuoghi, Osmar Aparecido

    2012-01-01

    Impaction of maxillary canines can be prevented by early intervention in the mixed dentition phase after the correct diagnosis of malocclusion, reducing the complexity of the treatment. This article reports the case of a 10-year-old patient who possessed impacted maxillary canines and, after early extraction of primary canines, had reestablished favorable permanent successors' eruption axis. This 5-year radiographic follow-up study with panoramic radiography shows that this can be used in practice and that an effective control strategy ensures the accuracy in the inclination of the impacted canines. Treatment success is related to early diagnosis and strategic interceptive treatment choice.

  7. Impaired translocation and activation of mitochondrial Akt1 mitigated mitochondrial oxidative phosphorylation Complex V activity in diabetic myocardium.

    PubMed

    Yang, Jia-Ying; Deng, Wu; Chen, Yumay; Fan, Weiwei; Baldwin, Kenneth M; Jope, Richard S; Wallace, Douglas C; Wang, Ping H

    2013-06-01

    Insulin can translocate Akt to mitochondria in cardiac muscle. The goals of this study were to define sub-mitochondrial localization of the translocated Akt, to dissect the effects of insulin on Akt isoform translocation, and to determine the direct effect of mitochondrial Akt activation on Complex V activity in normal and diabetic myocardium. The translocated Akt sequentially localized to the mitochondrial intermembrane space, inner membrane, and matrix. To confirm Akt translocation, in vitro import assay showed rapid entry of Akt into mitochondria. Akt isoforms were differentially regulated by insulin stimulation, only Akt1 translocated into mitochondria. In the insulin-resistant Type 2 diabetes model, Akt1 translocation was blunted. Mitochondrial activation of Akt1 increased Complex V activity by 24% in normal myocardium in vivo and restored Complex V activity in diabetic myocardium. Basal mitochondrial Complex V activity was lower by 22% in the Akt1(-/-) myocardium. Insulin-stimulated Complex V activity was not impaired in the Akt1(-/-) myocardium, due to compensatory translocation of Akt2 to mitochondria. Akt1 is the primary isoform that relayed insulin signaling to mitochondria and modulated mitochondrial Complex V activity. Activation of mitochondrial Akt1 enhanced ATP production and increased phosphocreatine in cardiac muscle cells. Dysregulation of this signal pathway might impair mitochondrial bioenergetics in diabetic myocardium.

  8. Syndecan-4 proteoliposomes enhance fibroblast growth factor-2 (FGF-2)–induced proliferation, migration, and neovascularization of ischemic muscle

    PubMed Central

    Jang, Eugene; Albadawi, Hassan; Watkins, Michael T.; Edelman, Elazer R.; Baker, Aaron B.

    2012-01-01

    Ischemia of the myocardium and lower limbs is a common consequence of arterial disease and a major source of morbidity and mortality in modernized countries. Inducing neovascularization for the treatment of ischemia is an appealing therapeutic strategy for patients for whom traditional treatment modalities cannot be performed or are ineffective. In the past, the stimulation of blood vessel growth was pursued using direct delivery of growth factors, angiogenic gene therapy, or cellular therapy. Although therapeutic angiogenesis holds great promise for treating patients with ischemia, current methods have not found success in clinical trials. Fibroblast growth factor-2 (FGF-2) was one of the first growth factors to be tested for use in therapeutic angiogenesis. Here, we present a method for improving the biological activity of FGF-2 by codelivering the growth factor with a liposomally embedded coreceptor, syndecan-4. This technique was shown to increase FGF-2 cellular signaling, uptake, and nuclear localization in comparison with FGF-2 alone. Delivery of syndecan-4 proteoliposomes also increased endothelial proliferation, migration, and angiogenic tube formation in response to FGF-2. Using an animal model of limb ischemia, syndecan-4 proteoliposomes markedly improved the neovascularization following femoral artery ligation and recovery of perfusion of the ischemic limb. Taken together, these results support liposomal delivery of syndecan-4 as an effective means to improving the potential of using growth factors to achieve therapeutic neovascularization of ischemic tissue. PMID:22307630

  9. An iso-integral mapping technique using magnetocardiogram, and its possible use for diagnosis of ischemic heart disease.

    PubMed

    Tsukada, K; Miyashita, T; Kandori, A; Mitsui, T; Terada, Y; Sato, M; Shiono, J; Horigome, H; Yamada, S; Yamaguchi, I

    2000-02-01

    We have developed an iso-integral mapping technique that uses magneto-cardiogram (MCG) data to obtain a map as projected total current image on the torso from the heart. We have also investigated the applicability of iso-integral mapping to the diagnosis of ischemic heart disease. We simulated and measured the characteristics of two types of iso-integral maps: one using tangential (Bxy) components, and one using the normal component (Bz). Each vector component was measured by two types of superconducting quantum interference device (SQUID) system to determine the tangential and normal components. The tangential component of the magnetic field appeared to be equivalent to the current image in the myocardium projected on the observing plane, and we were able to obtain a projected total current image by integration of the tangential components during the depolarization and repolarization processes. And we found that the iso-integral maps of normal hearts showed similar pattern in both processes; however, those of ischemic hearts showed different patterns.

  10. Resilience in Patients with Ischemic Heart Disease

    PubMed Central

    de Lemos, Conceição Maria Martins; Moraes, David William; Pellanda, Lucia Campos

    2016-01-01

    Background Resilience is a psychosocial factor associated with clinical outcomes in chronic diseases. The relationship between this protective factor and certain diseases, such heart diseases, is still under-explored. Objective The present study sought to investigate the frequency of resilience in individuals with ischemic heart disease. Method This was a cross-sectional study with 133 patients of both genders, aged between 35 and 65 years, treated at Rio Grande do Sul Cardiology Institute - Cardiology University Foundation, with a diagnosis of ischemic heart disease during the study period. Sixty-seven patients had a history of acute myocardial infarction. The individuals were interviewed and evaluated by the Wagnild & Young resilience scale and a sociodemographic questionnaire. Results Eighty-one percent of patients were classified as resilient according to the scale. Conclusion In the sample studied, resilience was identified in high proportion among patients with ischemic heart disease. PMID:26815312

  11. Mitral valve repair for ischemic mitral regurgitation.

    PubMed

    Mohebali, Jahan; Chen, Frederick Y

    2015-05-01

    Mitral valve repair for ischemic mitral valve regurgitation remains controversial. In moderate mitral regurgitation (MR), controversy exists whether revascularization alone will be adequate to restore native valve geometry or whether intervention on the valve (repair) should be performed concomitantly. When MR is severe, the need for valve intervention is not disputed. Rather, the controversy is whether repair versus replacement should be undertaken. In contrast to degenerative or myxomatous disease that directly affects leaflet integrity and morphology, ischemic FMR results from a distortion and dilation of native ventricular geometry that normally supports normal leaflet coaptation. To address this, the first and most crucial step in successful valve repair is placement of an undersized, complete remodeling annuloplasty ring to restore the annulus to its native geometry. The following article outlines the steps for repair of ischemic mitral regurgitation.

  12. Spectroscopic monitoring of kidney tissue ischemic injury

    NASA Astrophysics Data System (ADS)

    Fitzgerald, Jason T.; Michalopoulou, Andromachi P.; Troppmann, Christoph; Demos, Stavros G.

    2004-07-01

    Noninvasive evaluation of tissue viability of donor kidneys used for transplantation is an issue that current technology is not able to address. In this work, we explore optical spectroscopy for its potential to assess the degree of ischemic damage in kidney tissue. We hypothesized that ischemic damage to kidney tissue will give rise to changes in its optical properties which in turn may be used to asses the degree of tissue injury. The experimental results demonstrate that the autofluorescence intensity of the injured kidney is decreasing as a function of time exposed to ischemic injury. Changes were also observed in the NIR light scattering intensities most probably arising from changes due to injury and death of the tissue.

  13. Spectroscopic Monitoring of Kidney Tissue Ischemic Injury

    SciTech Connect

    Demos, S G; Fitzgerald, J T; Michalopoulou, A P; Troppmann, C

    2004-03-11

    Noninvasive evaluation of tissue viability of donor kidneys used for transplantation is an issue that current technology is not able to address. In this work, we explore optical spectroscopy for its potential to assess the degree of ischemic damage in kidney tissue. We hypothesized that ischemic damage to kidney tissue will give rise to changes in its optical properties which in turn may be used to asses the degree of tissue injury. The experimental results demonstrate that the autofluorescence intensity of the injured kidney is decreasing as a function of time exposed to ischemic injury. Changes were also observed in the NIR light scattering intensities most probably arising from changes due to injury and death of the tissue.

  14. Abnormalities of capillary microarchitecture in a rat model of coronary ischemic congestive heart failure.

    PubMed

    Chen, Jiqiu; Yaniz-Galende, Elisa; Kagan, Heather J; Liang, Lifan; Hekmaty, Saboor; Giannarelli, Chiara; Hajjar, Roger

    2015-04-15

    The aim of the present study is to explore the role of capillary disorder in coronary ischemic congestive heart failure (CHF). CHF was induced in rats by aortic banding plus ischemia-reperfusion followed by aortic debanding. Coronary arteries were perfused with plastic polymer containing fluorescent dye. Multiple fluorescent images of casted heart sections and scanning electric microscope of coronary vessels were obtained to characterize changes in the heart. Cardiac function was assessed by echocardiography and in vivo hemodynamics. Stenosis was found in all levels of the coronary arteries in CHF. Coronary vasculature volume and capillary density in remote myocardium were significantly increased in CHF compared with control. This occurred largely in microvessels with a diameter of ≤3 μm. Capillaries in CHF had a tortuous structure, while normal capillaries were linear. Capillaries in CHF had inconsistent diameters, with assortments of narrowed and bulged segments. Their surfaces appeared rough, potentially indicating endothelial dysfunction in CHF. Segments of main capillaries between bifurcations were significantly shorter in length in CHF than in control. Transiently increasing preload by injecting 50 μl of 30% NaCl demonstrated that the CHF heart had lower functional reserve; this may be associated with congestion in coronary microcirculation. Ischemic coronary vascular disorder is not limited to the main coronary arteries, as it occurs in arterioles and capillaries. Capillary disorder in CHF included stenosis, deformed structure, proliferation, and roughened surfaces. This disorder in the coronary artery architecture may contribute to the reduction in myocyte contractility in the setting of heart failure.

  15. Myocardial regeneration by activation of multipotent cardiac stem cells in ischemic heart failure

    NASA Astrophysics Data System (ADS)

    Urbanek, Konrad; Torella, Daniele; Sheikh, Farooq; de Angelis, Antonella; Nurzynska, Daria; Silvestri, Furio; Beltrami, C. Alberto; Bussani, Rossana; Beltrami, Antonio P.; Quaini, Federico; Bolli, Roberto; Leri, Annarosa; Kajstura, Jan; Anversa, Piero

    2005-06-01

    In this study, we tested whether the human heart possesses a cardiac stem cell (CSC) pool that promotes regeneration after infarction. For this purpose, CSC growth and senescence were measured in 20 hearts with acute infarcts, 20 hearts with end-stage postinfarction cardiomyopathy, and 12 control hearts. CSC number increased markedly in acute and, to a lesser extent, in chronic infarcts. CSC growth correlated with the increase in telomerase-competent dividing CSCs from 1.5% in controls to 28% in acute infarcts and 14% in chronic infarcts. The CSC mitotic index increased 29-fold in acute and 14-fold in chronic infarcts. CSCs committed to the myocyte, smooth muscle, and endothelial cell lineages increased 85-fold in acute infarcts and 25-fold in chronic infarcts. However, p16INK4a-p53-positive senescent CSCs also increased and were 10%, 18%, and 40% in controls, acute infarcts, and chronic infarcts, respectively. Old CSCs had short telomeres and apoptosis involved 0.3%, 3.8%, and 9.6% of CSCs in controls, acute infarcts, and chronic infarcts, respectively. These variables reduced the number of functionally competent CSCs from 26,000/cm3 of viable myocardium in acute to 7,000/cm3 in chronic infarcts, respectively. In seven acute infarcts, foci of spontaneous myocardial regeneration that did not involve cell fusion were identified. In conclusion, the human heart possesses a CSC compartment, and CSC activation occurs in response to ischemic injury. The loss of functionally competent CSCs in chronic ischemic cardiomyopathy may underlie the progressive functional deterioration and the onset of terminal failure. cardiac progenitor cells | human heart | myocardial infarction

  16. Role of platelet-activating factor in polymorphonuclear neutrophil recruitment in reperfused ischemic rabbit heart.

    PubMed Central

    Montrucchio, G.; Alloatti, G.; Mariano, F.; Comino, A.; Cacace, G.; Polloni, R.; De Filippi, P. G.; Emanuelli, G.; Camussi, G.

    1993-01-01

    This study investigated the role of platelet-activating factor in the recruitment of polymorphonuclear neutrophils (PMN) in a rabbit model of cardiac ischemia and reperfusion. The accumulation of PMN was evaluated 2 and 24 hours after removal of 40 minutes of coronary occlusion by morphometric analysis and 111In-labeled PMN infiltration. The administration of two structurally unrelated platelet-activating factor-receptor antagonists (SDZ 63-675, 5 mg/kg body weight, and WEB 2170, 5 mg/kg body weight) before reperfusion significantly reduced the accumulation of PMN, as well as the hemodynamic alterations and the size of necrotic area. Two hours after reperfusion, the percentage of increase of 111In-labeled PMN in transmural central ischemic zone was significantly reduced in rabbits pretreated with SDZ 63-675 (51.4 +/- 7.9) or WEB 2170 (32.4 +/- 8.8) with respect to untreated rabbits (107.6 +/- 13.5). The morphometric analysis of myocardial sections confirmed the reduction of PMN infiltration at 2 hours and demonstrated that at 24 hours the phenomenon was even more significant. In addition, SDZ 63-675 and WEB 2170 prevented early transient bradycardia and hypotension and reduced the infarct size, judged by staining with tetrazolium at 2 and 24 hours after reperfusion, and by histological examination at 24 hours. These results suggest that platelet-activating factor is involved in the accumulation of PMN in the reperfused ischemic myocardium and contributes to the evolution of myocardial injury. Images Figure 5 Figure 6 PMID:8434642

  17. Abnormalities of capillary microarchitecture in a rat model of coronary ischemic congestive heart failure

    PubMed Central

    Chen, Jiqiu; Yaniz-Galende, Elisa; Kagan, Heather J.; Liang, Lifan; Hekmaty, Saboor; Giannarelli, Chiara

    2015-01-01

    The aim of the present study is to explore the role of capillary disorder in coronary ischemic congestive heart failure (CHF). CHF was induced in rats by aortic banding plus ischemia-reperfusion followed by aortic debanding. Coronary arteries were perfused with plastic polymer containing fluorescent dye. Multiple fluorescent images of casted heart sections and scanning electric microscope of coronary vessels were obtained to characterize changes in the heart. Cardiac function was assessed by echocardiography and in vivo hemodynamics. Stenosis was found in all levels of the coronary arteries in CHF. Coronary vasculature volume and capillary density in remote myocardium were significantly increased in CHF compared with control. This occurred largely in microvessels with a diameter of ≤3 μm. Capillaries in CHF had a tortuous structure, while normal capillaries were linear. Capillaries in CHF had inconsistent diameters, with assortments of narrowed and bulged segments. Their surfaces appeared rough, potentially indicating endothelial dysfunction in CHF. Segments of main capillaries between bifurcations were significantly shorter in length in CHF than in control. Transiently increasing preload by injecting 50 μl of 30% NaCl demonstrated that the CHF heart had lower functional reserve; this may be associated with congestion in coronary microcirculation. Ischemic coronary vascular disorder is not limited to the main coronary arteries, as it occurs in arterioles and capillaries. Capillary disorder in CHF included stenosis, deformed structure, proliferation, and roughened surfaces. This disorder in the coronary artery architecture may contribute to the reduction in myocyte contractility in the setting of heart failure. PMID:25659485

  18. Mapping lubricin in canine musculoskeletal tissues.

    PubMed

    Sun, Yulong; Berger, Evelyn J; Zhao, Chunfeng; An, Kai-Nan; Amadio, Peter C; Jay, Gregory

    2006-01-01

    Lubricin, also known as superficial zone protein or PRG4, has many distinct biological functions, including lubrication, antiadhesion, and as a regulator of cell growth. This study investigated lubricin in canine musculoskeletal tissues using RT-PCR and immunohistochemistry. One or more variants were noted in canine flexor digitorum profundus (FDP) tendon, Achilles tendon, patellar tendon, A2 pulley, anterior cruciate ligament (ACL), knee lateral collateral ligament (LCL), articular cartilage, meniscus, muscle, and skin. We found 6 N-terminal lubricin splicing variants. The variants with larger sizes were identified in FDP tendon, ACL, LCL, A2 pulley, and cartilage. Lubricin was distributed both on the tissue surfaces and at the interface of fiber bundles within tissues, but this distribution varied by tissue type. We conclude that lubricin is present in many tissues; variations in splicing and physical distribution suggest that the variants of lubricin may play different roles in different locations.

  19. Reevaluating canine perspective-taking behavior.

    PubMed

    Udell, Monique A R; Wynne, Clive D L

    2011-12-01

    Udell, Dorey, and Wynne (2011) demonstrated that both domesticated and nondomesticated canids-specifically, gray wolves-have the capacity to succeed on perspective-taking tasks, suggesting that dogs' ability to respond to the human attentional state is not a by-product of domestication alone. Furthermore, not all dogs were successful on the task. Instead, the occluder type used was a strong predictor of performance, indicating the important role of environment and experience for tasks of this type. Here, we address several commentaries reflecting on the methods and design of that study, as well as the interpretation of the results. We also discuss the positive shift toward more interactive approaches in the field of canine behavior and cognition. Finally, we question the functionality of describing canine social behavior in terms of theory of mind.

  20. Drug Delivery to the Ischemic Brain

    PubMed Central

    Thompson, Brandon J.; Ronaldson, Patrick T.

    2014-01-01

    Cerebral ischemia occurs when blood flow to the brain is insufficient to meet metabolic demand. This can result from cerebral artery occlusion that interrupts blood flow, limits CNS supply of oxygen and glucose, and causes an infarction/ischemic stroke. Ischemia initiates a cascade of molecular events inneurons and cerebrovascular endothelial cells including energy depletion, dissipation of ion gradients, calcium overload, excitotoxicity, oxidative stress, and accumulation of ions and fluid. Blood-brain barrier (BBB) disruption is associated with cerebral ischemia and leads to vasogenic edema, a primary cause of stroke-associated mortality. To date, only a single drug has received US Food and Drug Administration (FDA) approval for acute ischemic stroke treatment, recombinant tissue plasminogen activator (rt-PA). While rt-PA therapy restores perfusion to ischemic brain, considerable tissue damage occurs when cerebral blood flow is re-established. Therefore, there is a critical need for novel therapeutic approaches that can “rescue” salvageable brain tissue and/or protect BBB integrity during ischemic stroke. One class of drugs that may enable neural cell rescue following cerebral ischemia/reperfusion injury is the HMG-CoA reductase inhibitors (i.e., statins). Understanding potential CNS drug delivery pathways for statins is critical to their utility in ischemic stroke. Here, we review molecular pathways associated with cerebral ischemia and novel approaches for delivering drugs to treat ischemic disease. Specifically, we discuss utility of endogenous BBB drug uptake transporters such as organic anion transporting polypeptides (OATPs/Oatps) and nanotechnology-based carriers for optimization of CNS drug delivery. Overall, this chapter highlights state-of-the-art technologies that may improve pharmacotherapy of cerebral ischemia. PMID:25307217

  1. Serologic investigations of canine parvovirus and canine distemper in relation to wolf (Canis lupus) pup mortalities.

    PubMed

    Johnson, M R; Boyd, D K; Pletscher, D H

    1994-04-01

    Twenty-one serum samples from 18 wolves (Canis lupus) were collected from 1985 to 1990 from northwestern Montana (USA) and southeastern British Columbia, Canada, and evaluated for antibodies to canine parvovirus (CPV), canine distemper (CD), infectious canine hepatitis, and Lyme disease; we found prevalences of 13 (65%) of 19, five (29%) of 17, seven (36%) of 19, and 0 of 20 wolves for these diseases, respectively. Pups died or disappeared in three of the eight packs studied. In these three packs, adult pack members had CPV titers > or = 1,600 or CD titers > or = 1,250. In packs that successfully raised pups, CPV and CD titers were low. We propose that CPV or CD may have caused some pup mortalities.

  2. [Restoration of canine guidance using bonded prostheses].

    PubMed

    Maroto García, J; Maroto García, F

    1989-11-01

    The aim of this paper is to offer an easy, accurate and aesthetical solution to the problem of the loss, by wastage, of anterior guides in those patients who show facets in initial stages of bruxism (central of peripheral). Using the acid-etch non-precious metals(Cr-Ni-Be) technique we make a metalic plaque covering the posterior face of the upper canines, on which we place a porcelain incisal rim. All of this is fixed with a composed material.

  3. Tyrosine Kinase Receptor Expression in Canine Liposarcoma.

    PubMed

    Avallone, G; Pellegrino, V; Roccabianca, P; Lepri, E; Crippa, L; Beha, G; De Tolla, L; Sarli, G

    2017-03-01

    The expression of tyrosine kinase receptors is attracting major interest in human and veterinary oncological pathology because of their role as targets for adjuvant therapies. Little is known about tyrosine kinase receptor (TKR) expression in canine liposarcoma (LP), a soft tissue sarcoma. The aim of this study was to evaluate the immunohistochemical expression of the TKRs fibroblast growth factor receptor 1 (FGFR1) and platelet-derived growth factor receptor-β (PDGFRβ); their ligands, fibroblast growth factor 2 (FGF2) and platelet-derived growth factor B (PDGFB); and c-kit in canine LP. Immunohistochemical labeling was categorized as high or low expression and compared with the mitotic count and MIB-1-based proliferation index. Fifty canine LPs were examined, classified, and graded. Fourteen cases were classified as well differentiated, 7 as myxoid, 25 as pleomorphic, and 4 as dedifferentiated. Seventeen cases were grade 1, 26 were grade 2, and 7 were grade 3. A high expression of FGF2, FGFR1, PDGFB, and PDGFRβ was identified in 62% (31/50), 68% (34/50), 81.6% (40/49), and 70.8% (34/48) of the cases, respectively. c-kit was expressed in 12.5% (6/48) of the cases. Mitotic count negatively correlated with FGF2 ( R = -0.41; P < .01), being lower in cases with high FGF2 expression, and positively correlated with PDGFRβ ( R = 0.33; P < .01), being higher in cases with high PDGFRβ expression. No other statistically significant correlations were identified. These results suggest that the PDGFRβ-mediated pathway may have a role in the progression of canine LP and may thus represent a promising target for adjuvant cancer therapies.

  4. The treatment of canine demodecosis with amitraz.

    PubMed

    Davis, D A

    1985-03-01

    The treatment of a series of 27 clinical cases of canine demodecosis is reported. Three of 4 applications of a wash containing 0,025% amitraz, together with antimicrobial and antipruritic therapy where necessary, were sufficient to effect clinical cure in 25 out of 26 cases mildly to severely affected. In one case, very severely affected, 9 weekly applications, together with antimicrobial and antipruritic therapy, effected clinical and parasitological cure.

  5. Anterior ischemic optic neuropathy following dengue fever.

    PubMed

    Ramakrishnan, Reshma; Shrivastava, Saurabh; Deshpande, Shrikant; Patkar, Priyanka

    2016-01-01

    Dengue fever is caused by a flavivirus. This infection is endemic in the tropics and warm temperate regions of the world. Ocular manifestations of dengue fever include subconjunctival, vitreous, and retinal haemorrhages; posterior uveitis; optic neuritis; and maculopathies, haemorrhage, and oedema. However anterior ischemic optic neuropathy is a rare presentation. Optic nerve ischemia most frequently occurs at the optic nerve head, where structural crowding of nerve fibers and reduction of the vascular supply may combine to impair perfusion to a critical degree and produce optic disc oedema. Here we present a case of anterior ischemic optic neurapathy associated with dengue fever.

  6. Anterior ischemic optic neuropathy following dengue fever

    PubMed Central

    Ramakrishnan, Reshma; Shrivastava, Saurabh; Deshpande, Shrikant; Patkar, Priyanka

    2016-01-01

    Dengue fever is caused by a flavivirus. This infection is endemic in the tropics and warm temperate regions of the world. Ocular manifestations of dengue fever include subconjunctival, vitreous, and retinal haemorrhages; posterior uveitis; optic neuritis; and maculopathies, haemorrhage, and oedema. However anterior ischemic optic neuropathy is a rare presentation. Optic nerve ischemia most frequently occurs at the optic nerve head, where structural crowding of nerve fibers and reduction of the vascular supply may combine to impair perfusion to a critical degree and produce optic disc oedema. Here we present a case of anterior ischemic optic neurapathy associated with dengue fever. PMID:27843231

  7. Ischemic Gastropathic Ulcer Mimics Gastric Cancer

    PubMed Central

    Daher, Saleh; Lahav, Ziv; Rmeileh, Ayman Abu; Mizrahi, Meir

    2016-01-01

    Gastric ulcer due to mesenteric ischemia is a rare clinical finding. As a result, few reports of ischemic gastric ulcers have been reported in the literature. The diagnosis of ischemic gastropathy is seldom considered in patients presenting with abdominal pain and gastric ulcers. In this case report, we describe a patient with increasing abdominal pain, weight loss, and gastric ulcers, who underwent extensive medical evaluation and whose symptoms were resistant to medical interventions. Finally he was diagnosed with chronic mesenteric ischemia, and his clinical and endoscopic abnormalities resolved after surgical revascularization of both the superior mesenteric artery and the celiac trunk. PMID:27579191

  8. Ischemic Gastropathic Ulcer Mimics Gastric Cancer.

    PubMed

    Daher, Saleh; Lahav, Ziv; Rmeileh, Ayman Abu; Mizrahi, Meir; Khoury, Tawfik

    2016-01-01

    Gastric ulcer due to mesenteric ischemia is a rare clinical finding. As a result, few reports of ischemic gastric ulcers have been reported in the literature. The diagnosis of ischemic gastropathy is seldom considered in patients presenting with abdominal pain and gastric ulcers. In this case report, we describe a patient with increasing abdominal pain, weight loss, and gastric ulcers, who underwent extensive medical evaluation and whose symptoms were resistant to medical interventions. Finally he was diagnosed with chronic mesenteric ischemia, and his clinical and endoscopic abnormalities resolved after surgical revascularization of both the superior mesenteric artery and the celiac trunk.

  9. Increasing Incidence of Canine Leptospirosis in Switzerland

    PubMed Central

    Major, Andrea; Schweighauser, Ariane; Francey, Thierry

    2014-01-01

    A marked increase in canine leptospirosis was observed in Switzerland over 10 years with a peak incidence of 28.1 diagnosed cases/100,000 dogs/year in the most affected canton. With 95% affected dogs living at altitudes <800 m, the disease presented a seasonal pattern associated with temperature (r2 0.73) and rainfall (r2 0.39), >90% cases being diagnosed between May and October. The increasing yearly incidence however was only weakly correlated with climatic data including number of summer (r2 0.25) or rainy days (r2 0.38). Serovars Australis and Bratislava showed the highest seropositivity rates with 70.5% and 69.1%, respectively. Main clinical manifestations included renal (99.6%), pulmonary (76.7%), hepatic (26.0%), and hemorrhagic syndromes (18.2%), leading to a high mortality rate (43.3%). Similar to the human disease, liver involvement had the strongest association with negative outcome (OR 16.3). Based on these data, canine leptospirosis presents similar features and severity as the human infection for which it therefore can be considered a model. Its re-emergence in a temperate country with very high incidence rates in canines should thus be viewed as a warning and emphasize the need for increased awareness in other species. PMID:25032740

  10. Enhancing stem cell survival in an ischemic heart by CRISPR-dCas9-based gene regulation.

    PubMed

    Pan, Alexander; Weintraub, Neal L; Tang, Yaoliang

    2014-12-01

    Ischemic heart disease has remained the number one killer around the world for over the past 20 years. While stem cell therapy has become a promising new frontier to repair the damaged heart, limited stem cell survivability post-transplantation has precluded widespread use of this therapy. Strategies to genetically modify stem cells to activate pro-survival and anti-apoptotic and anti-inflammatory pathways, such as Akt and heme oxygenase-1, have been shown to improve the lifespan of transplanted stem cells within the ischemic myocardium, but constitutive overexpression of these pathways at high levels has been shown to have side effects. Therefore, more specific and controlled gene activation would be necessary. Current techniques used for gene regulation include zinc finger and TALE proteins, but there are still disadvantages to each of these methods, such as ease and cost of use. Also, those methods use synthesized promoters to express synthesized cDNA, which lack regulatory elements, including introns and 3' untranslated regions for microRNA mediated post-transcriptional regulation. A new novel technique, the CRISPR/dCas9 system, was recently developed as a simple and efficient method for endogenous gene regulation. With its use of single guide chimeric RNA's (sgRNA's), this system has been shown to provide a high level of specificity and efficiency. When targeting different loci, past studies have found that the CRISPR/dCas9 system can activate gene expression at varying levels. In addition, this system makes use of the genome's endogenous regulatory elements, such as the aforementioned introns and 3' UTR's, which can help provide a safer method of gene activation. If targeted to a gene promoting cellular survival or decreasing cell death, it could potentially improve stem cell longevity in a more efficient and controllable manner. As a result, our hypothesis is to use the CRISPR/dCas9 system to activate expression of an anti-inflammatory and anti

  11. Transgenic mice expressing the human heat shock protein 70 have improved post-ischemic myocardial recovery.

    PubMed Central

    Plumier, J C; Ross, B M; Currie, R W; Angelidis, C E; Kazlaris, H; Kollias, G; Pagoulatos, G N

    1995-01-01

    Heat shock treatment induces expression of several heat shock proteins and subsequent post-ischemic myocardial protection. Correlations exist between the degree of stress used to induce the heat shock proteins, the amount of the inducible heat shock protein 70 (HSP70) and the level of myocardial protection. The inducible HSP70 has also been shown to be protective in transfected myogenic cells. Here we examined the role of human inducible HSP70 in transgenic mouse hearts. Overexpression of the human HSP70 does not appear to affect normal protein synthesis or the stress response in transgenic mice compared with nontransgenic mice. After 30 min of ischemia, upon reperfusion, transgenic hearts versus nontransgenic hearts showed significantly improved recovery of contractile force (0.35 +/- 0.08 versus 0.16 +/- 0.05 g, respectively, P < 0.05), rate of contraction, and rate of relaxation. Creatine kinase, an indicator of cellular injury, was released at a high level (67.7 +/- 23.0 U/ml) upon reperfusion from nontransgenic hearts, but not transgenic hearts (1.6 +/- 0.8 U/ml). We conclude that high level constitutive expression of the human inducible HSP70 plays a direct role in the protection of the myocardium from ischemia and reperfusion injury. Images PMID:7706492

  12. A Mouse Model for Fetal Maternal Stem Cell Transfer During Ischemic Cardiac Injury

    PubMed Central

    Kara, Rina J.; Bolli, Paola; Matsunaga, Iwao; Tanweer, Omar; Altman, Perry; Chaudhry, Hina W.

    2012-01-01

    Fetal cells enter the maternal circulation during pregnancies and can persist in blood and tissues for decades, creating a state of physiologic microchimerism. Microchimerism refers to acquisition of cells from another individual and can be due to bi-directional cell traffic between mother and fetus during pregnancy. Peripartum cardiomyopathy, a rare cardiac disorder associated with high mortality rates has the highest recovery rate amongst all etiologies of heart failure although the reason is unknown. Collectively, these observations led us to hypothesize that fetal cells enter the maternal circulation and may be recruited to the sites of myocardial disease or injury. The ability to genetically modify mice makes them an ideal system for studying the phenomenon of microchimerism in cardiac disease. Described here is a mouse model for ischemic cardiac injury during pregnancy designed to study microchimerism. Wild-type virgin female mice mated with eGFP male mice underwent ligation of the left anterior descending artery to induce a myocardial infarction at gestation day 12. We demonstrate the selective homing of eGFP cells to the site of cardiac injury without such homing to nonfinjured tissues suggesting the presence of precise signals sensed by fetal cells enabling them to target diseased myocardium specifically. PMID:22883609

  13. Restoration of myocardial bioenergetic metabolism in swine after periods of ischemic ventricular fibrillation.

    PubMed

    Skinner, F P; Levitzky, M G; Scott, R F; Fricks, J

    1975-05-01

    Myocardial mitochondrial function and high energy phosphate levels were measured in normal swine, in swine after either 5 or 10 minutes of ischemic ventricular fibrillation (IVF) while on cardiopulmonary bypass, and in swine defibrillated after either 5 or 10 minutes of IVE. The damage to myocardial mitochondria induced by IVF, such as partial uncoupling, decreased oxygen uptake, and loss of cytochrome oxidase activity, was completely reversed almost instantly by coronary artery perfusion and the restoration of sinus rhythm. After either 5 or 10 minutes of IVF followed by coronary artery reperfusion and defibrillation, myocardial creatine phosphate (CP), adenosine monophosphate (AMP) and adenosine diphosphate (ADP) return to normal levels very rapidly. However, adenosine triphosphate (ATP) levels remain significantly lower than control levels. If the bioenergetic mechanisms of swine and human myocardium are similar, it appears that IVF at least for a 10 minute period produces no damage to myocardial mitochondria that is not corrected by perfusion of the coronary arteries and re-establishment of sinus rhythm. Furthermore, sinus rhythm can be re-established and maintained despite signficantly lower levels of myocardial ATP.

  14. In-vivo assessment of normal T1 values of the right-ventricular myocardium by cardiac MRI.

    PubMed

    Kawel-Boehm, N; Dellas Buser, T; Greiser, A; Bieri, O; Bremerich, J; Santini, F

    2014-02-01

    To test feasibility of myocardial T1 mapping of the right ventricle (RV) at systole when myocardium is more compact and to determine the most appropriate imaging plane. 20 healthy volunteers (11 men; 33 ± 8 years) were imaged on a 1.5T scanner (MAGNETOM Avanto, Siemens AG, Erlangen, Germany). A modified look-locker inversion-recovery sequence was acquired at mid-ventricular short axis (SAX), as horizontal long-axis view and as transversal view at systole (mean trigger time 363 ± 37 ms). Myocardial T1 time of the left-ventricular and RV myocardium was measured within a region of interest (ROI) on generated T1-maps. The most appropriate imaging plane for the RV was determined by the ability to draw a ROI including the largest amount of myocardium without including adjacent tissue or blood. At systole, when myocardium is thicker, measurements of the RV myocardium were feasible in 18/20 subjects. Average size of the ROI was 0.42 ± 0.28 cm(2). In 10/18 subjects, short axis was the most appropriate imaging plane to obtain measurements (p = 0.034). Average T1 time of the RV myocardium was 1,016 ± 61 ms, and average T1 of the left-ventricular (LV) was 956 ± 25 ms (p < 0.001). T1 mapping of the RV myocardium is feasible during systole in the majority of healthy subjects but with a small ROI only. SAX plane was the optimal imaging plane in the majority of subjects. Native myocardial T1 time of the RV is significantly longer compared to the LV, which might be explained by the naturally higher collagen content of the RV.

  15. Luxury perfusion following anterior ischemic optic neuropathy.

    PubMed

    Friedland, S; Winterkorn, J M; Burde, R M

    1996-09-01

    We present five patients who developed luxury perfusion following anterior ischemic optic neuropathy in whom fluorescein angiography was misinterpreted as "capillary hemangioma" or neovascularization of the disc. In each case, the segment of disc hyperemia corresponded to a spared region of visual field. Luxury perfusion represents a reparative autoregulatory reaction to ischemia.

  16. 9 CFR 113.317 - Parvovirus Vaccine (Canine).

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 9 Animals and Animal Products 1 2014-01-01 2014-01-01 false Parvovirus Vaccine (Canine). 113.317... Virus Vaccines § 113.317 Parvovirus Vaccine (Canine). Parvovirus Vaccine recommended for use in dogs... pure, safe, and immunogenic shall be used for preparing seeds for vaccine production. All serials...

  17. 9 CFR 113.317 - Parvovirus Vaccine (Canine).

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 9 Animals and Animal Products 1 2012-01-01 2012-01-01 false Parvovirus Vaccine (Canine). 113.317... Virus Vaccines § 113.317 Parvovirus Vaccine (Canine). Parvovirus Vaccine recommended for use in dogs... pure, safe, and immunogenic shall be used for preparing seeds for vaccine production. All serials...

  18. 9 CFR 113.317 - Parvovirus Vaccine (Canine).

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Parvovirus Vaccine (Canine). 113.317... Virus Vaccines § 113.317 Parvovirus Vaccine (Canine). Parvovirus Vaccine recommended for use in dogs... pure, safe, and immunogenic shall be used for preparing seeds for vaccine production. All serials...

  19. 9 CFR 113.317 - Parvovirus Vaccine (Canine).

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 9 Animals and Animal Products 1 2013-01-01 2013-01-01 false Parvovirus Vaccine (Canine). 113.317... Virus Vaccines § 113.317 Parvovirus Vaccine (Canine). Parvovirus Vaccine recommended for use in dogs... pure, safe, and immunogenic shall be used for preparing seeds for vaccine production. All serials...

  20. 9 CFR 113.317 - Parvovirus Vaccine (Canine).

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 9 Animals and Animal Products 1 2011-01-01 2011-01-01 false Parvovirus Vaccine (Canine). 113.317... Virus Vaccines § 113.317 Parvovirus Vaccine (Canine). Parvovirus Vaccine recommended for use in dogs... pure, safe, and immunogenic shall be used for preparing seeds for vaccine production. All serials...

  1. Sex differences in anthropoid mandibular canine lateral enamel formation.

    PubMed

    Guatelli-Steinberg, Debbie; Ferrell, Rebecca J; Spence, Jennifer; Talabere, Tiffany; Hubbard, Amelia; Schmidt, Stacey

    2009-10-01

    Previous research has demonstrated that great ape and macaque males achieve large canine crown sizes primarily through extended canine growth periods. Recent work has suggested, however, that platyrrhine males may achieve larger canine sizes by accelerating rather than prolonging growth. This study tested the hypothesis that the ontogenetic pathway leading to canine sexual dimorphism in catarrhines differs from that of platyrrhines. To test this hypothesis, males and females of several catarrhine genera (Hylobates, Papio, Macaca, Cercopithecus, and Cercocebus) and three platyrrhine genera (Cebus, Ateles, and Callicebus) were compared in the number and spacing of perikymata (enamel growth increments) on their canine crowns. In addition, perikymata periodicities (the number of days of growth perikymata represent) were determined for five genera (Hylobates, Papio, Macaca, Cebus, and Ateles) using previously published as well as original data gathered for this study. The central findings are as follows: 1) males have more perikymata than females for seven of eight genera (in five of the seven, the differences are statistically significant); 2) in general, the greater the degree of sexual dimorphism, the greater the sex difference in male and female perikymata numbers; 3) there is no evidence of a systematic sex difference in primate periodicities; and 4) there is some evidence that sex differences in enamel formation rates may make a minor contribution to canine sexual dimorphism in Papio and Cercopithecus. These findings strongly suggest that in both catarrhines and platyrrhines prolongation of male canine growth is the primary mechanism by which canine crown sexual dimorphism is achieved.

  2. Canine tooth size and fitness in male mandrills (Mandrillus sphinx).

    PubMed

    Leigh, Steven R; Setchell, Joanna M; Charpentier, Marie; Knapp, Leslie A; Wickings, E Jean

    2008-07-01

    Sexual selection theory explains the evolution of exaggerated male morphologies and weaponry, but the fitness consequences of developmental and age-related changes in these features remain poorly understood. This long-term study of mandrill monkeys (Mandrillus sphinx) demonstrates how age-related changes in canine tooth weaponry and adult canine size correlate closely with male lifetime reproductive success. Combining long-term demographic and morphometric data reveals that male fitness covaries simply and directly with canine ontogeny, adult maximum size, and wear. However, fitness is largely independent of other somatometrics. Male mandrills sire offspring almost exclusively when their canines exceed approximately 30 mm, or two-thirds of average adult value (45 mm). Moreover, sires have larger canines than nonsires. The tooth diminishes through wear as animals age, corresponding with, and perhaps influencing, reproductive senescence. These factors combine to constrain male reproductive opportunities to a brief timespan, defined by the period of maximum canine length. Sexually-selected weaponry, especially when it is nonrenewable like the primate canine tooth, is intimately tied to the male life course. Our analyses of this extremely dimorphic species indicate that sexual selection is closely intertwined with growth, development, and aging, pointing to new directions for sexual selection theory. Moreover, the primate canine tooth has potential as a simple mammalian system for testing genetically-based models of aging. Finally, the tooth may record details of life histories in fossil primates, especially when sexual selection has played a role in the evolution of dimorphism.

  3. Limitations of the mandibular canine index in sex assessment.

    PubMed

    Acharya, Ashith B; Mainali, Sneedha

    2009-02-01

    Measuring teeth is a useful adjunct in sex assessment. Canines, in particular, have the greatest degree of sexual dimorphism, resist disease and survive postmortem trauma, rendering them highly valuable in identification. Hence, their exclusive use in odontometric sex assessment using the Mandibular Canine Index (MCI) has been advocated before. The MCI is derived as the ratio of the mesiodistal (MD) dimension of canines and the inter-canine arch width. This study has tested the use of the MCI in assessing sex on a sample from Nepal and compared its accuracy to that of absolute canine measurements. Measurements were obtained from one hundred-and-seventeen dental stone casts that belonged to 63 males and 54 females, all young adults in the age-group 19-28 years. Independent samples t-test revealed no significant sexual dimorphism in the MCI. In addition, discriminant analysis of the MCI also had poor ability to differentiate the sexes. In contrast, the absolute canine measurements revealed statistically significant male-female difference and superior ability to differentiate sex using discriminant analysis. The poor ability of the MCI in sex assessment is attributed to it being a relative value-it is obtained as the ratio of two absolute measurements (MD dimension of canines and inter-canine arch width) and does not reflect sex differences that exist in the absolute measurements per se.

  4. First detection of canine parvovirus type 2c in Brazil

    PubMed Central

    Streck, André Felipe; de Souza, Carine Kunzler; Gonçalves, Karla Rathje; Zang, Luciana; Pinto, Luciane Dubina; Canal, Cláudio Wageck

    2009-01-01

    The presence of canine parvovirus type 2 (CPV-2), 2a and 2b has been described in Brazil, however, the type 2c had not been reported until now. In the current study, seven out of nine samples from dogs with diarrhea were characterized as CPV-2c, indicating that this virus is already circulating in the Brazilian canine population. PMID:24031389

  5. Canine evolution in sabretoothed carnivores: natural selection or sexual selection?

    PubMed

    Randau, Marcela; Carbone, Chris; Turvey, Samuel T

    2013-01-01

    The remarkable elongated upper canines of extinct sabretoothed carnivorous mammals have been the subject of considerable speculation on their adaptive function, but the absence of living analogues prevents any direct inference about their evolution. We analysed scaling relationships of the upper canines of 20 sabretoothed feliform carnivores (Nimravidae, Barbourofelidae, Machairodontinae), representing both dirk-toothed and scimitar-toothed sabretooth ecomorphs, and 33 non-sabretoothed felids in relation to body size in order to characterize and identify the evolutionary processes driving their development, using the scaling relationships of carnassial teeth in both groups as a control. Carnassials display isometric allometry in both sabretooths and non-sabretooths, supporting their close relationship with meat-slicing, whereas the upper canines of both groups display positive allometry with body size. Whereas there is no statistical difference in allometry of upper canine height between dirk-toothed and scimitar-toothed sabretooth ecomorphs, the significantly stronger positive allometry of upper canine height shown by sabretooths as a whole compared to non-sabretooths reveals that different processes drove canine evolution in these groups. Although sabretoothed canines must still have been effective for prey capture and processing by hypercarnivorous predators, canine morphology in these extinct carnivores was likely to have been driven to a greater extent by sexual selection than in non-sabretooths. Scaling relationships therefore indicate the probable importance of sexual selection in the evolution of the hypertrophied sabretooth anterior dentition.

  6. Adult treatment with removal of all four permanent canines.

    PubMed

    Freeman, R S

    1994-11-01

    The permanent canines-especially in the maxillary arch-have always been considered of prime importance, even before the "cuspid protection" hypothesis became well known to most orthodontists in the 1960s. In the adult case presented, periodontal considerations and other factors led to the unconventional (and likely controversial) extraction of all four canines.

  7. Morphology and immunoreactivity of canine and feline extramedullary plasmacytomas.

    PubMed

    Mikiewicz, M; Otrocka-Domagała, I; Paździor-Czapula, K; Gesek, M

    2016-01-01

    The aim of the study was the evaluation of morphology and immunophenotype of canine (19 cases) and feline (7 cases) extramedullary plasmacytomas. Tumours, located in skin, oral cavity and spleen were surgically excised, fixed and processed for histopathology and immunohistochemistry (CD79α, CD18, proliferating cell nuclear antigen, metallothionein). Histologically, tumours were classified into mature, cleaved, asynchronous, polymorphous blastic, hyalin, or monomorphous blastic type. All evaluated tumours showed cytoplasmic expression of CD79α antigen. The expression of CD18 was observed in canine cutaneous and splenic tumours. In canine tumours expression of metallothionein was low to moderate, while in feline plasmacytomas - absent or low. In canine tumours, the mitotic index and proliferating cell nuclear antigen index were positively correlated with the expression of metallothionein. In feline tumours no correlation between mitotic index, proliferating cell nuclear antigen and metallothionein was found. This is the first study describing expression of metallothionein in canine and feline extramedullary plasmacytoma.

  8. RAS gene hot-spot mutations in canine neoplasias.

    PubMed

    Richter, A; Murua Escobar, H; Günther, K; Soller, J T; Winkler, S; Nolte, I; Bullerdiek, J

    2005-01-01

    Point mutations in the cellular homologues HRAS, KRAS2, and NRAS of the viral Harvey and Kirsten rat sarcoma virus oncogenes are commonly involved in the onset of malignancies in humans and other species such as dog, mouse, and rat. Most often, three particular hot-spot codons are affected, with one amino acid exchange being sufficient for the induction of tumor growth. While RAS genes have been shown to play an important role in canine tumors such as non-small lung cell carcinomas, data about RAS mutations in canine fibrosarcomas as well as KRAS2 mutations in canine melanomas is sparse. To increase the number of tumors examined, we recently screened 13 canine fibrosarcomas and 11 canine melanomas for point mutations, particularly within the mutational hot spots. The results were compared to the already existing data from other studies about these tumors in dogs.

  9. Canine brain tumours: a model for the human disease?

    PubMed

    Hicks, J; Platt, S; Kent, M; Haley, A

    2017-03-01

    Canine brain tumours are becoming established as naturally occurring models of disease to advance diagnostic and therapeutic understanding successfully. The size and structure of the dog's brain, histopathology and molecular characteristics of canine brain tumours, as well as the presence of an intact immune system, all support the potential success of this model. The limited success of current therapeutic regimens such as surgery and radiation for dogs with intracranial tumours means that there can be tremendous mutual benefit from collaboration with our human counterparts resulting in the development of new treatments. The similarities and differences between the canine and human diseases are described in this article, emphasizing both the importance and limitations of canines in brain tumour research. Recent clinical veterinary therapeutic trials are also described to demonstrate the areas of research in which canines have already been utilized and to highlight the important potential benefits of translational research to companion dogs.

  10. Reliability of mandibular canine and mandibular canine index in sex determination: A study using Uyghur population.

    PubMed

    Iqbal, Raza; Zhang, Shuang; Mi, Congbo

    2015-07-01

    Sex determination is a key process that is required to establish the forensic profile of an individual. Mandibular canine index (MCI) method yields fairly positive results for sex determination. However, this method has been challenged by a few authors. This study aimed to examine the reliability of MCI in Chinese Uyghur population and to establish its normal value for this ethnic group. Dental casts of 216 students (117 males and 119 females) from the College of Stomatology of Xinjiang Medical University in China were used to determine the sexing accuracy of MCI. The mesiodistal (MD) dimension of mandibular canine crowns, the inter-canine distance, and the MCI were calculated. The accuracy of the standard MCI derived from the current data was compared with that of the standard MCIs derived from previous data. Results were statistically described using the independent-samples t-test. The MD dimension of mandibular crown, the inter-canine distance, and the MCI exhibited statistically significant sexual dimorphism. Sex determination using the MCI derived from the current data revealed fairly reliable results. Therefore, MCI is a reliable method for sex determination for Uyghur population, with 0.248 as standard MCI value.

  11. Recombinant canine distemper virus serves as bivalent live vaccine against rabies and canine distemper.

    PubMed

    Wang, Xijun; Feng, Na; Ge, Jinying; Shuai, Lei; Peng, Liyan; Gao, Yuwei; Yang, Songtao; Xia, Xianzhu; Bu, Zhigao

    2012-07-20

    Effective, safe, and affordable rabies vaccines are still being sought. Attenuated live vaccine has been widely used to protect carnivores from canine distemper. In this study, we generated a recombinant canine distemper virus (CDV) vaccine strain, rCDV-RVG, expressing the rabies virus glycoprotein (RVG) by using reverse genetics. The recombinant virus rCDV-RVG retained growth properties similar to those of vector CDV in Vero cell culture. Animal studies demonstrated that rCDV-RVG was safe in mice and dogs. Mice inoculated intracerebrally or intramuscularly with rCDV-RVG showed no apparent signs of disease and developed a strong rabies virus (RABV) neutralizing antibody response, which completely protected mice from challenge with a lethal dose of street virus. Canine studies showed that vaccination with rCDV-RVG induced strong and long-lasting virus neutralizing antibody responses to RABV and CDV. This is the first study demonstrating that recombinant CDV has the potential to serve as bivalent live vaccine against rabies and canine distemper in animals.

  12. Nosocomial Outbreak of Serious Canine Infectious Tracheobronchitis (Kennel Cough) Caused by Canine Herpesvirus Infection▿

    PubMed Central

    Kawakami, Kazuo; Ogawa, Hiroyuki; Maeda, Ken; Imai, Ayako; Ohashi, Emi; Matsunaga, Satoru; Tohya, Yukinobu; Ohshima, Takahisa; Mochizuki, Masami

    2010-01-01

    Canine herpesvirus (CHV; Canid herpesvirus 1) is principally a perinatal pathogen of pregnant bitches and newborn pups and secondarily a respiratory tract pathogen of older pups and dogs. Infectious disease of the canine respiratory tract frequently occurs among dogs in groups, in which it is called “ infectious tracheobronchitis” (ITB). Mortality from ITB is generally negligible, and the clinical importance of CHV as an ITB pathogen is considered to be low. The present report describes a novel ITB outbreak accompanied by death among aged dogs in an animal medical center. Most inpatient dogs had received medications that could induce immunosuppression. CHV was the only pathogen identified, and several CHV isolates were recovered in cell culture. No other viral pathogens or significant bacterial pathogens were found. Molecular and serological analyses revealed that the causative CHV isolates were from a single source but that none was a peculiar strain when the strains were compared with previous CHV strains. The virus had presumably spread among the dogs predisposed to infection in the center. The present results serve as a warning to canine clinics that, under the specific set of circumstances described, such serious CHV outbreaks may be expected wherever canine ITB occurs. PMID:20107103

  13. Cardiomyocyte-specific ablation of CD36 improves post-ischemic functional recovery.

    PubMed

    Nagendran, Jeevan; Pulinilkunnil, Thomas; Kienesberger, Petra C; Sung, Miranda M; Fung, David; Febbraio, Maria; Dyck, Jason R B

    2013-10-01

    Although pre-clinical evidence has suggested that partial inhibition of myocardial fatty acid oxidation (FAO) and subsequent switch to greater glucose oxidation for ATP production can prevent ischemia/reperfusion injury, controversy about this approach persists. For example, mice with germline deletion of the FA transporter CD36, exhibited either impaired or unchanged post-ischemic functional recovery despite a 40-60% reduction in FAO rates. Because there are limitations to cardiac studies utilizing whole body CD36 knockout (totalCD36KO) mice, we have now generated an inducible and cardiomyocyte-specific CD36 KO (icCD36KO) mouse to better address the role of cardiomyocyte CD36 and its regulation of FAO and post-ischemic functional recovery. Four to six weeks following CD36 ablation, hearts from icCD36KO mice had significantly decreased FA uptake compared to controls, which was paralleled by significant reductions in intramyocardial triacylglycerol content. Analysis of cardiac energy metabolism using ex vivo working heart perfusions showed that reduced FAO rates were compensated by enhanced glucose oxidation in the hearts from icCD36KO mice. In contrast to the totalCD36KO mice, hearts from icCD36KO mice exhibited significantly improved functional recovery following ischemia/reperfusion (18min of global no-flow ischemia followed by 40min of aerobic reperfusion). This improved recovery was associated with lower calculated proton production prior to and following ischemia compared to controls. Moreover, the amount of ATP generated relative to cardiac work was significantly lower in the hearts from icCD36KO mice compared to controls, indicating significantly increased cardiac efficiency in the hearts from icCD36KO mice. These data provide genetic evidence that reduced FAO as a result of diminished CD36-mediated FA uptake improves post-ischemic cardiac efficiency and functional recovery. As such, targeting cardiomyocyte FA uptake and FAO via inhibition of CD36 in the

  14. Analysis of immune cell populations in atrial myocardium of patients with atrial fibrillation or sinus rhythm

    PubMed Central

    Smorodinova, Natalia; Bláha, Martin; Melenovský, Vojtěch; Rozsívalová, Karolína; Přidal, Jaromír; Ďurišová, Mária; Pirk, Jan; Kautzner, Josef; Kučera, Tomáš

    2017-01-01

    Background Atrial fibrillation (AF) is the most common arrhythmia and despite obvious clinical importance remains its pathogenesis only partially explained. A relation between inflammation and AF has been suggested by findings of increased inflammatory markers in AF patients. Objective The goal of this study was to characterize morphologically and functionally CD45-positive inflammatory cell populations in atrial myocardium of patients with AF as compared to sinus rhythm (SR). Methods We examined 46 subjects (19 with AF, and 27 in SR) undergoing coronary bypass or valve surgery. Peroperative bioptic samples of the left and the right atrial tissue were examined using immunohistochemistry. Results The number of CD3+ T-lymphocytes and CD68-KP1+ cells were elevated in the left atrial myocardium of patients with AF compared to those in SR. Immune cell infiltration of LA was related to the rhythm, but not to age, body size, LA size, mitral regurgitation grade, type of surgery, systemic markers of inflammation or presence of diabetes or hypertension. Most of CD68-KP1+ cells corresponded to dendritic cell population based on their morphology and immunoreactivity for DC-SIGN. The numbers of mast cells and CD20+ B-lymphocytes did not differ between AF and SR patients. No foci of inflammation were detected in any sample. Conclusions An immunohistochemical analysis of samples from patients undergoing open heart surgery showed moderate and site-specific increase of inflammatory cells in the atrial myocardium of patients with AF compared to those in SR, with prevailing population of monocyte-macrophage lineage. These cells and their cytokine products may play a role in atrial remodeling and AF persistence. PMID:28225836

  15. Sympathetic denervation of peri-infarct myocardium requires the p75 neurotrophin receptor.

    PubMed

    Lorentz, Christina U; Parrish, Diana C; Alston, Eric N; Pellegrino, Michael J; Woodward, William R; Hempstead, Barbara L; Habecker, Beth A

    2013-11-01

    Development of cardiac sympathetic heterogeneity after myocardial infarction contributes to ventricular arrhythmias and sudden cardiac death. Regions of sympathetic hyperinnervation and denervation appear in the viable myocardium beyond the infarcted area. While elevated nerve growth factor (NGF) is implicated in sympathetic hyperinnervation, the mechanisms underlying denervation are unknown. Recent studies show that selective activation of the p75 neurotrophin receptor (p75(NTR)) in sympathetic neurons causes axon degeneration. We used mice that lack p75(NTR) to test the hypothesis that activation of p75(NTR) causes peri-infarct sympathetic denervation after cardiac ischemia-reperfusion. Wild type hearts exhibited sympathetic denervation adjacent to the infarct 24h and 3 days after ischemia-reperfusion, but no peri-infarct sympathetic denervation occurred in p75(NTR)-/- mice. Sympathetic hyperinnervation was found in the distal peri-infarct myocardium in both genotypes 3 days after MI, and hyperinnervation was increased in the p75(NTR)-/- mice. By 7 days after ischemia-reperfusion, cardiac sympathetic innervation density returned back to sham-operated levels in both genotypes, indicating that axonal pruning did not require p75(NTR). Prior studies revealed that proNGF is elevated in the damaged left ventricle after ischemia-reperfusion, as is mRNA encoding brain-derived neurotrophic factor (BDNF). ProNGF and BDNF preferentially bind p75(NTR) rather than TrkA on sympathetic neurons. Immunohistochemistry using Bdnf-HA mice confirmed the presence of BDNF or proBDNF in the infarct after ischemia-reperfusion. Thus, at least two p75(NTR) ligands are elevated in the left ventricle after ischemia-reperfusion where they may stimulate p75(NTR)-dependent denervation of peri-infarct myocardium. In contrast, NGF-induced sympathetic hyperinnervation in the distal peri-infarct ventricle is attenuated by p75(NTR).

  16. Cyclooxygenase blockade limits blood flow to collateral-dependent myocardium during exercise.

    PubMed

    Altman, J D; Klassen, C L; Bache, R J

    1995-11-01

    Cyclooxygenase blockade has been found to cause vasoconstriction of coronary collateral vessels in open-chest animals. This study was carried out to determine whether cyclooxygenase blockade can limit blood flow to collateral-dependent myocardium during exercise. Studies were performed in 8 adult mongrel dogs in which intermittent followed by permanent occlusion of the left anterior descending coronary artery produced an area of collateral-dependent myocardium. Myocardial blood flow was measured with radioactive microspheres at rest and during treadmill exercise to produce heart rates of 215 +/-0 7 beats/min. At rest collateral zone blood flow (1.00 +/- 0.10 ml/min per g) was significantly less than normal zone flow (1.23 +/- 0.14) (P < 0.05). During control exercise blood flow increased 91 +/- 22% in the collateral zone and 102 +/- 28% in the normal zone (each P < 0.05). Thirty minutes after cyclooxygenase blockade with indomethacin (5 mg/kg i.v.) blood flow in the normal zone and the collateral zone was not different from control during resting conditions. Indomethacin did not change heart rate or arterial pressure during exercise, but significantly increased the aortic-to-distal coronary pressure gradient from 33 +/- 3 to 40 +/- 5 mmHg (P < 0.05). Indomethacin increased transcollateral resistance during exercise by 42 +/- 10% (P < 0.05); this was associated with a 27 +/- 11% decrease in subendocardial flow in the collateral zone (P < 0.05) with no significant change in subepicardial flow, and no change in normal zone blood flow. These findings demonstrate that in the intact awake animal cyclooxygenase blockade causes coronary collateral vasoconstriction which can impair blood flow to the dependent myocardium during exercise.

  17. Electrophysiological studies of the interaction between ventricular myocardium and coronary artery in monkeys.

    PubMed Central

    Mekata, F

    1994-01-01

    1. The electrical influence of the coronary arteries on ventricular muscle was investigated using strips of ventricle that included a section of coronary artery (cardiac preparation) and isolated coronary arteries dissected from the ventricle (arterial preparation). 2. In cardiac preparations, a hyperpolarizing response was recorded from the epicardial surface of the ventricular muscle when acetylcholine (ACh) was added to the organ bath, on condition that the internal diameter of the coronary artery was between 0.15 and 0.6 mm, that the vessel ran at a depth of 0.2 mm or less below the surface of the preparation, and that the recording microelectrode was immediately adjacent to the artery. 3. ACh-induced hyperpolarization was not detected in cardiac preparations which had no detectable arteries, or at sites distant from visible arteries. 4. In arterial preparations, a similar hyperpolarizing response was evoked by ACh in all vessels with an i.d. of 0.15-1.2 mm. 5. In a preparation combining ventricular muscle and a strip of coronary artery (with the vascular endothelium in direct contact with the epicardial surface of the ventricular myocardium), hyperpolarization was also observed from the ventricular muscle after application of ACh. 6. The hyperpolarizing response of the ventricular myocardium in the cardiac preparation and in combined preparations of ventricular muscle and coronary artery was weakened or abolished by removal of the arterial endothelium. 7. These results indicate that some substance released from the coronary arterial endothelium after stimulation by ACh induces hyperpolarization of the ventricular myocardium. PMID:7869248

  18. Effects of acute and chronic uremia on active cation transport in rat myocardium

    SciTech Connect

    Druml, W.; Kelly, R.A.; England, B.K.; O'Hara, D.S.; Mitch, W.E. )

    1990-12-01

    As abnormalities of active cation transport could contribute to the genesis of uremic cardiomyopathy, we investigated myocardial sodium pump function in rats with acute renal failure (ARF) and with a model of experimental chronic renal failure (CRF) that has metabolic similarities to advanced chronic uremia in humans. CRF rats were hypertensive and had left ventricular hypertrophy (33% higher heart:body weight ratio; P less than 0.01) at four weeks compared to pair-fed sham-operated rats. Importantly, both ouabain- and furosemide-sensitive 86Rb uptake rates were unchanged in left ventricular myocardial slices from CRF, and the intracellular sodium concentration was not different from that of control rats even though skeletal muscle sodium was increased, as we found previously. Insulin-stimulated, ouabain-sensitive 86Rb influx was also preserved. There also were no abnormalities in myocardium cation transport in rats with ARF. However, (3H)ouabain binding was decreased 45% in CRF rats (P less than 0.01); it was unchanged in acute uremia. Decreased ouabain binding in chronic uremia was due entirely to fewer low affinity (3H)ouabain binding sites (the binding affinity for ouabain was unaffected). We conclude that in chronic, (but not acute) renal failure, sodium pump number is reduced in myocardium but intracellular sodium is unchanged and active cation flux rates are maintained. These results emphasize that in rats with chronic uremia, intracellular sodium homeostasis is preserved in myocardium, despite the presence of marked abnormalities of active cation transport in skeletal muscle that are characteristic of chronic uremia.

  19. Anisotropic physical properties of myocardium characterized by ultrasonic measurements of backscatter, attenuation, and velocity

    NASA Astrophysics Data System (ADS)

    Baldwin, Steven L.

    The goal of elucidating the physical mechanisms underlying the propagation of ultrasonic waves in anisotropic soft tissue such as myocardium has posed an interesting and largely unsolved problem in the field of physics for the past 30 years. In part because of the vast complexity of the system being studied, progress towards understanding and modeling the mechanisms that underlie observed acoustic parameters may first require the guidance of careful experiment. Knowledge of the causes of observed ultrasonic properties in soft tissue including attenuation, speed of sound, and backscatter, and how those properties are altered with specific pathophysiologies, may lead to new noninvasive approaches to the diagnosis of disease. The primary aim of this Dissertation is to contribute to an understanding of the physics that underlies the mechanisms responsible for the observed interaction of ultrasound with myocardium. To this end, through-transmission and backscatter measurements were performed by varying acoustic properties as a function of angle of insonification relative to the predominant myofiber direction and by altering the material properties of myocardium by increased protein cross-linking induced by chemical fixation as an extreme form of changes that may occur in certain pathologies such as diabetes. Techniques to estimate acoustic parameters from backscatter were broadened and challenges to implementing these techniques in vivo were addressed. Provided that specific challenges identified in this Dissertation can be overcome, techniques to estimate attenuation from ultrasonic backscatter show promise as a means to investigate the physical interaction of ultrasound with anisotropic biological media in vivo. This Dissertation represents a step towards understanding the physics of the interaction of ultrasonic waves with anisotropic biological media.

  20. Effects of hypodynamia on the hemocoagulative properties of the vascular wall and myocardium

    NASA Technical Reports Server (NTRS)

    Inchina, V. I.

    1980-01-01

    The hemocoagulative properties of the aorta (laminar), myocardium, hollow veins, and fibrinolytic capacity of tissues were studied in 14 rabbits subjected to 7 days of restricted mobility and compared to those of 10 control animals. Two tables of results show that, as a result of hypodynamia, the thromboplastic activity of the inner and middle layers of the aorta together with the destruction of endothelium increases the hemocoagulative potential and creates the threat of thrombogenesis. There is also an increase in fibrin-stabilizing activity for all tissues.

  1. [The aspects of adenylate cyclase activity regulation in myocardium cell membranes during hypokinesia].

    PubMed

    Bulanova, K Ia; Komar, E S; Lobanok, L M

    1999-01-01

    Nonstimulated and isoproterenol, GTF, GITF, NaF stimulated activities of the adenylate cyclase in sarcolemma in white rats' myocardium was studied after two weeks of hypokinesia. As was established, in restrained animals the sensitivity of adenylate cyclase to the specified agents was increased and transition to the bimodal GTF regulation took place. It is hypothesised that involvement of membrane-bound Gi-proteins in the adrenergic effects on cardiomyocytes is one of mechanisms of the cardiotropic effects of restraint and heart distresses.

  2. Regional Stress-Induced Ischemia in Non-fibrotic Hypertrophied Myocardium in Young HCM Patients.

    PubMed

    Jablonowski, Robert; Fernlund, Eva; Aletras, Anthony H; Engblom, Henrik; Heiberg, Einar; Liuba, Petru; Arheden, Håkan; Carlsson, Marcus

    2015-12-01

    The relationship between hypertrophy, perfusion abnormalities and fibrosis is unknown in young patients with hypertrophic cardiomyopathy (HCM). Since mounting evidence suggests causal relationship between myocardial ischemia and major adverse cardiac events, we sought to investigate whether (1) regional myocardial perfusion is decreased in young HCM patients and in individuals at risk of HCM, and (2) hypoperfused areas are larger than areas with fibrosis. HCM patients (n = 12), HCM-risk subjects (n = 15) and controls (n = 9) were imaged on a 1.5 T MRI scanner. Myocardial hypertrophy was assessed on cine images. Perfusion images were acquired during adenosine hyperemia and at rest. Maximum upslope ratios of perfusion (stress/rest) were used for semiquantitative analysis. Fibrosis was assessed by late gadolinium enhancement (LGE). Results are presented as median and range. Perfusion in HCM-risk subjects and in non-hypertrophied segments in HCM patients showed no difference compared to controls (P = ns). Hypertrophic segments in HCM patients without LGE showed decreased perfusion compared to segments without hypertrophy [1.5 (1.1-2.3) vs. 2.0 (1.8-2.6), P < 0.001], and hypertrophic segments with LGE showed even lower perfusion using a segmental analysis [0.9 (0.6-1.8), P < 0.05]. The extent of hypoperfused myocardium in HCM patients during adenosine exceeded the extent of fibrosis on LGE [20 (0-48) vs. 4 (0-7) % slice area, P < 0.05] and hypoperfused areas at rest (P < 0.001). Regional perfusion is decreased in hypertrophied compared to non-hypertrophied myocardium and is lowest in fibrotic myocardium in young HCM patients but does not discriminate HCM-risk subjects from controls. The stress-induced hypoperfused regions exceed regions with LGE, indicating that hypoperfusion precedes fibrosis and may be a more sensitive marker of diseased myocardium in HCM.

  3. Viscoelastic properties of pressure overload hypertrophied myocardium: effect of serine protease treatment

    NASA Technical Reports Server (NTRS)

    Stroud, Jason D.; Baicu, Catalin F.; Barnes, Mary A.; Spinale, Francis G.; Zile, Michael R.

    2002-01-01

    To determine whether and to what extent one component of the extracellular matrix, fibrillar collagen, contributes causally to abnormalities in viscoelasticity, collagen was acutely degraded by activation of endogenous matrix metalloproteinases (MMPs) with the serine protease plasmin. Papillary muscles were isolated from normal cats and cats with right ventricular pressure overload hypertrophy (POH) induced by pulmonary artery banding. Plasmin treatment caused MMP activation, collagen degradation, decreased the elastic stiffness constant, and decreased the viscosity constant in both normal and POH muscles. Thus, whereas many mechanisms may contribute to the abnormalities in myocardial viscoelasticity in the POH myocardium, changes in fibrillar collagen appear to play a predominant role.

  4. Challenging mitral valve repair for double-orifice mitral valve with noncompaction of left ventricular myocardium.

    PubMed

    Yamasaki, Manabu; Misumi, Hiroyasu; Abe, Kohei; Kawazoe, Kohei

    2017-02-25

    Double-orifice mitral valve (DOMV) is a relatively rare cardiac anomaly. Although usually associated with various cardiac anomalies, co-presence of DOMV and noncompaction of left ventricular myocardium (NCLVM) is extremely rare. Here, we present a 24-year-old male who underwent mitral valve repair using artificial chordae and annuloplasty at the posterior commissure for severe mitral regurgitation (MR), resulting from flail anterior leaflet of the larger postero-medial orifice and dilatation of left ventricle with NCLVM. One year later, he underwent second mitral valve repair for recurrence of MR. Further endoscopic evaluation of the left ventricle, and reinforcement via artificial ring, enabled us to achieve repair.

  5. [Antihypoxic effects of various derivatives of 3-hydroxypyridine on isolated rat myocardium].

    PubMed

    Luk'ianova, L D; Atabaeva, R E; Shepeleva, S Iu

    1993-04-01

    Antihypoxic effect of a succinate-containing derivative of hydroxypyridine = --mexidol and its analog--emoxipin on contractile function and energy exchange of rats' myocard was investigated. It was shown reliably that mexidole have more expressed protective properties in myocardium of low-resistant (but not high-resistant) rats. In case of antihypoxant emoxipin prohypoxic properties prevail. It have been proposed that antihypoxic activity of mexidol was linked with presence of succinate in composition of the substance, which can be oxidated in this conditions.

  6. Three-year duration of immunity in dogs following vaccination against canine adenovirus type-1, canine parvovirus, and canine distemper virus.

    PubMed

    Gore, Thomas C; Lakshmanan, Nallakannu; Duncan, Karen L; Coyne, Michael J; Lum, Melissa A; Sterner, Frank J

    2005-01-01

    A challenge-of-immunity study was conducted to demonstrate immunity in dogs 3 years after their second vaccination with a new multivalent, modified-live vaccine containing canine adenovirus type 2 (CAV-2), canine parvovirus (CPV), and canine distemper virus (CDV). Twenty-three seronegative pups were vaccinated at 7 and 11 weeks of age. Eighteen seronegative pups, randomized into groups of six dogs, served as challenge controls. Dogs were kept in strict isolation for 3 years following the vaccination and then challenged sequentially with virulent canine adenovirus type 1 (CAV-1), CPV, and CDV. For each viral challenge, a separate group of six control dogs was also challenged. Clinical signs of CAV-1, CPV, and CDV infections were prevented in 100% of vaccinated dogs, demonstrating that the multivalent, modified-live test vaccine provided protection against virulent CAV-1, CPV, and CDV challenge in dogs 7 weeks of age or older for a minimum of 3 years following second vaccination.

  7. Cloning and characterization of canine SHARP1 and its evaluation as a positional candidate for canine early retinal degeneration (erd).

    PubMed

    Kukekova, Anna V; Aguirre, Gustavo D; Acland, Gregory M

    2003-07-17

    Canine early retinal degeneration (erd) is an early onset form of canine progressive retinal atrophy phenotypically similar to human retinitis pigmentosa. In a previous study, the locus responsible for erd was mapped to canine chromosome 27 in the region corresponding to HSA12p, a region where no human retinal degeneration loci have been mapped. Canine SHARP1 gene has been localized on CFA27 in the erd interval by RH mapping, and considered as a positional candidate gene for erd. SHARP1 was cloned and sequenced from normal and erd affected dogs, and no disease-causing mutations were identified. Genotyping of 117 dogs from informative pedigrees did not reveal any recombinants between SHARP1 and erd. To date SHARP1 gene is the closest gene-specific marker to erd; genotyping additional informative pedigrees, and sequencing SHARP1 upstream regions from normal and affected dogs will be necessary to establish if SHARP1 is involved in this canine retinal disease.

  8. Extraglandular and intraglandular vascularization of canine prostate.

    PubMed

    Stefanov, Miroslav

    2004-03-01

    The literature on the vascularization of the canine prostate is reviewed and the clinical significance of prostate morphology is described. Scanning Electron Microscopy (SEM), combined with improved corrosion casting methods, reveal new morphological details that promise better diagnostics and treatment but also require expansion of clinical nomenclature. A proposal is made for including two previously unnamed veins in Nomina Anatomica Veterinaria (NAV). The canine prostate has two lobes with independent vascularization. Each lobe is supplied through the left and right a. prostatica, respectively. The a. prostatica sprouts three small vessels (cranial, middle, and caudal) towards the prostate gland. A. prostatica is a small-size artery whose wall structure is similar to the arteries of the muscular type. V. prostatica is a small-size valved vein. The canine prostate has capsular, parenchymal, and urethral vascular zones. The surface vessels of the capsule are predominantly veins and the diameter of arterial vessels is larger than that of the veins. The trabecular vessels are of two types: direct and branched. The prostate parenchyma is supplied by branches of the trabecular vessels. The periacinary capillaries are fenestrated and form a net in a circular pattern. The processes of the myoepithelial cells embrace both the acins and the periacinar capillaries. In the prostate ductal system. there are spermatozoa. The prostatic part of the urethra is supplied by an independent branch of a. prostatica. The prostatic urethral part is drained by v. prostatica, the vein of the urethral bulb and the ventral prostate veins. M. urethralis begins as early as the urethral prostatic part. The greater part of the white muscle fibers in m. urethralis suggest an enhanced anaerobic metabolism.

  9. Sarcolemmal Ca(2+)-entry through L-type Ca(2+) channels controls the profile of Ca(2+)-activated Cl(-) current in canine ventricular myocytes.

    PubMed

    Horváth, Balázs; Váczi, Krisztina; Hegyi, Bence; Gönczi, Mónika; Dienes, Beatrix; Kistamás, Kornél; Bányász, Tamás; Magyar, János; Baczkó, István; Varró, András; Seprényi, György; Csernoch, László; Nánási, Péter P; Szentandrássy, Norbert

    2016-08-01

    Ca(2+)-activated Cl(-) current (ICl(Ca)) mediated by TMEM16A and/or Bestrophin-3 may contribute to cardiac arrhythmias. The true profile of ICl(Ca) during an actual ventricular action potential (AP), however, is poorly understood. We aimed to study the profile of ICl(Ca) systematically under physiological conditions (normal Ca(2+) cycling and AP voltage-clamp) as well as in conditions designed to change [Ca(2+)]i. The expression of TMEM16A and/or Bestrophin-3 in canine and human left ventricular myocytes was examined. The possible spatial distribution of these proteins and their co-localization with Cav1.2 was also studied. The profile of ICl(Ca), identified as a 9-anthracene carboxylic acid-sensitive current under AP voltage-clamp conditions, contained an early fast outward and a late inward component, overlapping early and terminal repolarizations, respectively. Both components were moderately reduced by ryanodine, while fully abolished by BAPTA, but not EGTA. [Ca(2+)]i was monitored using Fura-2-AM. Setting [Ca(2+)]i to the systolic level measured in the bulk cytoplasm (1.1μM) decreased ICl(Ca), while application of Bay K8644, isoproterenol, and faster stimulation rates increased the amplitude of ICl(Ca). Ca(2+)-entry through L-type Ca(2+) channels was essential for activation of ICl(Ca). TMEM16A and Bestrophin-3 showed strong co-localization with one another and also with Cav1.2 channels, when assessed using immunolabeling and confocal microscopy in both canine myocytes and human ventricular myocardium. Activation of ICl(Ca) in canine ventricular cells requires Ca(2+)-entry through neighboring L-type Ca(2+) channels and is only augmented by SR Ca(2+)-release. Substantial activation of ICl(Ca) requires high Ca(2+) concentration in the dyadic clefts which can be effectively buffered by BAPTA, but not EGTA.

  10. Creation of distal canine limb lymphedema

    SciTech Connect

    Chen, H.C.; Pribaz, J.J.; O'Brien, B.M.; Knight, K.R.; Morrison, W.A.

    1989-06-01

    A canine model of distal limb lymphedema was established in order to study the treatment of this condition by lymph node transfer. This model was more difficult to establish than whole-limb lymphedema. Significant edema was achieved by a combination of preoperative irradiation and circumferential removal of skin from the irradiated areas followed by removal of the contents of the popliteal fossa. Despite these measures, it was not possible to produce lymphedema in every case, possibly because of the presence of lymphaticovenous shunts and panvascular compensation mechanisms.

  11. Definition, Classification, and Pathophysiology of Canine Glaucoma.

    PubMed

    Pizzirani, Stefano

    2015-11-01

    Glaucoma is a common ocular condition in humans and dogs leading to optic nerve degeneration and irreversible blindness. Primary glaucoma is a group of spontaneous heterogeneous diseases. Multiple factors are involved in its pathogenesis and these factors vary across human ethnic groups and canine breeds, so the clinical phenotypes are numerous and their classification can be challenging and remain superficial. Aging and oxidative stress are major triggers for the manifestation of disease. Multiple, intertwined inflammatory and biochemical cascades eventually alter cellular and extracellular physiology in the optic nerve and trabecular meshwork and lead to vision loss.

  12. Maxillary canine restoration: a case report.

    PubMed

    Morris, G A; Lehman, G A

    1999-09-01

    The replacement of a single tooth with osseointegrated dental implants presents a unique challenge to both the prosthodontist and the surgeon. When anterior teeth are replaced, it is difficult to design an occlusal scheme that will direct forces down the long axis of an implant. This is especially true when the canine is involved. Wide-diameter implants offer advantages, such as increased surface area of implant to bone, stronger prosthetics, stronger implants, and less screw loosening or breakage when compared to standard-diameter implants. The single-stage technique is advantageous in terms of soft-tissue predictability, and it eliminates the need for second-stage surgery.

  13. Beneficial effect of medicinal plants on the contractility of post-hypoxic isolated guinea pig atria - Potential implications for the treatment of ischemic-reperfusion injury.

    PubMed

    Bipat, Robbert; Toelsie, Jerry R; Magali, Indira; Soekhoe, Rubaina; Stender, Karin; Wangsawirana, Angelique; Oedairadjsingh, Krishan; Pawirodihardjo, Jennifer; Mans, Dennis R A

    2016-08-01

    Context Ischemic-reperfusion injury is accompanied by a decreased contractility of the myocardium. Positive-inotropic agents have proven useful for treating this condition but may exert serious side-effects. Objective In this study, aqueous preparations from Abelmoschus esculentus L. Moench (Malvaceae), Annona muricata L. (Annonaceae), Bixa orellana L. (Bixaceae), Cecropia peltata L. (Moraceae), Erythrina fusca Lour. (Fabaceae), Psidium guajava L. (Myrtaceae) and Terminalia catappa L. (Combretaceae) were evaluated for their ability to improve the decreased contractility of isolated guinea pig atria after hypoxic stress. Materials and methods Guinea pig atria isolated in Ringer-Locke buffer gassed with 100% O2 at 30 °C were exposed for 5 min to hypoxia, then allowed to recover in oxygenated buffer alone or containing a single plant extract (0.001-1 mg/mL). The contractility (g/s) and beating frequency (beats/min), as well as troponin C contents of the bathing solution (ng/mL), were determined and expressed as means ± SDs. Results The extracts of A. muricata, B. orellana, C. peltata and T. catappa caused an increase in the contractility compared to untreated atria of 340 ± 102%, 151 ± 13%, 141 ± 14% and 238 ± 44%, respectively. However, the latter two preparations increased the troponin C contents of the bathing solution to 36 ± 11 and 69 ± 33, compared to the value of 11 ± 3 ng/mL found with untreated atria. Conclusions Preparations from A. muricata and B. orellana may possess positive-inotropic properties which may improve the contractility of the post-hypoxic myocardium. Studies to assess their usefulness in ischemic-reperfusion injury are warranted.

  14. Amelioration of Isoproterenol-Induced Oxidative Damage in Rat Myocardium by Withania somnifera Leaf Extract

    PubMed Central

    Khalil, Md. Ibrahim; Ahmmed, Istiyak; Ahmed, Romana; Tanvir, E. M.; Afroz, Rizwana; Paul, Sudip; Gan, Siew Hua; Alam, Nadia

    2015-01-01

    We investigated the protective role of Withania somnifera leaf extract (WSLEt) on isoproterenol- (ISO-) induced myocardial infarction (MI) in rats. Subcutaneous injection of ISO (85 mg/kg body weight (b.w.)) administered to rats for two consecutive days caused a significant increase in cardiac troponin I (cTnI) levels and serum lipid profiles, as well as the activities of some marker enzymes. In addition to these diagnostic markers, there were increased levels of lipid peroxidation (LPO) and decreased activities of enzymatic antioxidants (superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GRx), and glutathione-S-transferase (GST)) in the myocardium. However, oral pretreatment (100 mg/kg b.w.) with WSLEt for 4 weeks elicited a significant cardioprotective activity by lowering the levels of cTnI, lipid profiles, and marker enzymes. The levels of LPO products were also significantly decreased. Elevated activities of antioxidant enzymes were also observed in rats pretreated with WSLEt. As further confirmed histopathologically, our findings strongly suggest that the cardioprotective effect of WSLEt on myocardium experiencing ISO-induced oxidative damage may be due to an augmentation of the endogenous antioxidant system and an inhibition of LPO in the myocardial membrane. We conclude that WSLEt confers some protection against oxidative damage in ISO-induced MI in rats. PMID:26539517

  15. Functional antagonism of β-adrenoceptor subtypes in the catecholamine-induced automatism in rat myocardium

    PubMed Central

    Boer, DC; Bassani, JWM; Bassani, RA

    2011-01-01

    BACKGROUND AND PURPOSE Myocardial automatism and arrhythmias may ensue during strong sympathetic stimulation. We sought to investigate the relevant types of adrenoceptor, as well as the role of phosphodiesterase (PDE) activity, in the production of catecholaminergic automatism in atrial and ventricular rat myocardium. EXPERIMENTAL APPROACH The effects of adrenoceptor agonists on the rate of spontaneous contractions (automatic response) and the amplitude of electrically evoked contractions (inotropic response) were determined in left atria and ventricular myocytes isolated from Wistar rats. KEY RESULTS Catecholaminergic automatism was Ca2+-dependent, as it required a functional sarcoplasmic reticulum to be exhibited. Although both α- and β-adrenoceptor activation caused inotropic stimulation, only β1-adrenoceptors seemed to mediate the induction of spontaneous activity. Catecholaminergic automatism was enhanced and suppressed by β2-adrenoceptor blockade and stimulation respectively. Inhibition of either PDE3 or PDE4 (by milrinone and rolipram, respectively) potentiated the automatic response of myocytes to catecholamines. However, only rolipram abolished the attenuation of automatism produced by β2-adrenoceptor stimulation. CONCLUSIONS AND IMPLICATIONS α- and β2-adrenoceptors do not seem to be involved in the mediation of catecholaminergic stimulation of spontaneous activity in atrial and ventricular myocardium. However, a functional antagonism of β1- and β2-adrenoceptor activation was identified, the former mediating catecholaminergic myocardial automatism and the latter attenuating this effect. Results suggest that hydrolysis of cAMP by PDE4 is involved in the protective effect mediated by β2-adrenoceptor stimulation. PMID:21091648

  16. Ultrasmall superparamagnetic particles of iron oxide (USPIO) MR imaging of infarcted myocardium in pigs.

    PubMed

    Kroft, L J; Doornbos, J; van der Geest, R J; van der Laarse, A; van der Meulen, H; de Roos, A

    1998-09-01

    The purpose of this study is to assess the potential value of ultrasmall superparamagnetic iron oxide (USPIO) for the detection of acute myocardial infarction by magnetic resonance (MR) imaging. Spin-echo magnetic resonance imaging of the heart was performed before, immediately after, and approximately 35 and 90 min after 30 micromol Fe/kg of USPIO administration in seven pigs with surgically induced myocardial infarction. Gradient-echo sequences were used to identify contraction abnormalities at the site of infarction. Myocardial signal intensities were measured using region-of-interest analysis in normal and infarcted myocardium. In addition, liver and lung signal intensities were measured. Pathologic correlation was performed after sacrificing the animals. The infarct area was located with wall-motion analysis. The site of infarction was confirmed at pathologic examination. The signal-intensity ratio between infarcted and normal myocardium was not significantly changed after USPIO administration at equilibrium stages (immediately after injection p = 0.64, at 35 min p = 0.32, at 90 min p = 0.73). The signal intensity of the liver decreased significantly after contrast administration (p < 0.05). For the lung, the change in signal intensity after USPIO administration was not significant. This pig model is well suited to study wall motion abnormalities after induction of acute myocardial infarction. USPIO-enhanced magnetic resonance imaging does not improve the visualization of acute myocardial infarction at equilibrium stage.

  17. Case report. Isolated left ventricular myocardium non-compaction: MR imaging findings from three cases.

    PubMed

    Junqueira, F P; Fernandes, F D B; Coutinho, A C; De Pontes, P V; Domingues, R C

    2009-02-01

    The purpose of this study is to report three cases of left ventricular myocardium non-compaction (LVNC), with emphasis on the MRI findings. From May 2006 to February 2007, three patients -- 2 females (6 years and 42 years of age) and 1 male (18 years of age) -- presented to our radiology department, two of them with fatigue, shortness of breath and episodes of syncope and arrhythmia, for further investigation by cardiac MRI because an apparent asymmetrical pattern of hypertrophy of the left ventricular myocardium was suspected by transthoracic echocardiography. The 18-year-old patient was only experiencing arrhythmia, and arrhythmogenic right ventricular dysplasia was suspected. The images (produced by a 1.5T MRI system) were interpreted by two experienced radiologists and post-processed with Argus software (Siemens, Germany) for ejection fraction calculation. In all three patients, MRI aided in the correct identification of prominent ventricular myocardial trabeculations and deep intertrabecular recesses communicating with the ventricular cavity, as well as areas of hypokinesia with depressed systolic function, and showed the absence of myocardial delayed enhancement and other structural heart defects. In conclusion, cardiac MRI was useful for correctly identifying this rare congenital heart disorder and appears to increase diagnostic accuracy. Although considered a rare anomaly, radiologists should be capable of recognizing LVNC, as current non-invasive imaging methods have increased the frequency of this diagnosis and timely detection is vital in considering early-stage transplantation.

  18. Myosin types and fiber types in cardiac muscle. II. Atrial myocardium

    PubMed Central

    1982-01-01

    Antibodies were produced against myosins isolated from the left atrial myocardium (anti-bAm) and the left ventricular myocardium (anti-bVm) of the bovine heart. Cross-reactive antibodies were removed by cross- absorption. Absorbed anti-bAm and anti-bVm were specific for the myosin heavy chains when tested by enzyme immunoassay combined with SDS gel electrophoresis. Indirect immunofluorescence was used to determine the reactivity of atrial muscle fibers to the two antibodies. Three populations of atrial muscle fibers were distinguished in the bovine heart: (a) fibers reactive with anti-bAm and unreactive with anti-bVm, like most fibers in the left atrium; (b) fibers reactive with both antibodies, especially numerous in the right atrium; (c) fibers reactive with anti-bVm and unreactive with anti-bAm, present only in the interatrial septum and in specific regions of the right atrium, such as the crista terminalis. These findings can be accounted for by postulating the existence of two distinct types of atrial myosin heavy chains, one of which is antigenically related to ventricular myosin. The tendency for fibers labeled by anti-bVm to occur frequently in bundles and their preferential distribution in the crista terminalis, namely along one of the main conduction pathways between the sinus node and the atrioventricular node, and in the interatrial septum, where different internodal tracts are known to converge, suggests that these fibers may be specialized for faster conduction. PMID:6218175

  19. Impairment of energy metabolism in intact residual myocardium of rat hearts with chronic myocardial infarction.

    PubMed Central

    Neubauer, S; Horn, M; Naumann, A; Tian, R; Hu, K; Laser, M; Friedrich, J; Gaudron, P; Schnackerz, K; Ingwall, J S

    1995-01-01

    The purpose of this study was to test the hypothesis that energy metabolism is impaired in residual intact myocardium of chronically infarcted rat heart, contributing to contractile dysfunction. Myocardial infarction (MI) was induced in rats by coronary artery ligation. Hearts were isolated 8 wk later and buffer-perfused isovolumically. MI hearts showed reduced left ventricular developed pressure, but oxygen consumption was unchanged. High-energy phosphate contents were measured chemically and by 31P-NMR spectroscopy. In residual intact left ventricular tissue, ATP was unchanged after MI, while creatine phosphate was reduced by 31%. Total creatine kinase (CK) activity was reduced by 17%, the fetal CK isoenzymes BB and MB increased, while the "adult" mitochondrial CK isoenzyme activity decreased by 44%. Total creatine content decreased by 35%. Phosphoryl exchange between ATP and creatine phosphate, measured by 31P-NMR magnetization transfer, fell by 50% in MI hearts. Thus, energy reserve is substantially impaired in residual intact myocardium of chronically infarcted rats. Because phosphoryl exchange was still five times higher than ATP synthesis rates calculated from oxygen consumption, phosphoryl transfer via CK may not limit baseline contractile performance 2 mo after MI. In contrast, when MI hearts were subjected to acute stress (hypoxia), mechanical recovery during reoxygenation was impaired, suggesting that reduced energy reserve contributes to increased susceptibility of MI hearts to acute metabolic stress. PMID:7883957

  20. Elevated expression of liver X receptor alpha (LXRα) in myocardium of streptozotocin-induced diabetic rats.

    PubMed

    Cheng, Yongxia; Liu, Guibo; Pan, Qian; Guo, Sufen; Yang, Xianghong

    2011-12-01

    The present study was designed to investigate the myocardial expression of liver X receptor alpha (LXRα) in a streptozotocin (STZ)-induced diabetic rat model. Immunohistochemical staining, quantitative real-time RT-PCR, and Western blot analysis were used to determine the expression of LXRα in the myocardium of STZ-induced diabetic rats. The myocardial expression of LXRα target genes, long-chain acyl-CoA synthetase 3 (ACSL3), fatty acid transporter protein (FAT/CD36), ATP-binding cassette transporter A1 (ABCA1), and ABCG1 were also detected. Bisulfite sequencing analysis was employed to examine the methylation status of the CpG island at the LXRα promoter region in the myocardium of STZ-induced diabetic rats. We found that LXRα mRNA and protein expression in the left ventricles, right ventricles, and atria of diabetic rats were gradually increased during the progression of diabetic cardiomyopathy (DCM). The mRNA expression levels of ACSL3 and FAT/CD36 and the protein expression levels of ABCA1 and ABCG1 were also markedly increased in different heart chambers of diabetic rats. Moreover, there was a significant difference in the methylation status of LXRα gene between the ventricles of control and diabetic rats (P < 0.05). Our findings suggest that elevated expression of LXRα may be involved in the progression of DCM, and demethylation of LXRα is likely to be responsible for its increased expression in myocardial tissues.

  1. ULTRASTRUCTURAL ALTERATIONS PRODUCED IN MAMMALIAN MYOCARDIUM BY VARIATION IN PERFUSATE IONIC COMPOSITION

    PubMed Central

    Legato, Marianne J.; Spiro, David; Langer, Glenn A.

    1968-01-01

    This study describes the changes produced in the subcellular morphology of mammalian myocardium when perfusate sodium, calcium, and chloride concentrations are varied. By means of a recently developed perfusion technique, functioning dog papillary muscles were perfused with isotonic solutions of varying ionic compositions. Examination of the tissue in the electron microscope revealed that control muscles showed satisfactory preservation of ultrastructure, demonstrating that the protocol itself did not create significant morphological artefact. Low sodium chloride perfusion produced dilatation of both transverse tubules and longitudinal sarcoplasmic reticulum elements. Low sodium or high calcium concentrations produced dilation of tubular elements of the longitudinal sarcoplasmic reticulum while leaving transverse tubules intact. High calcium perfusion produced mitochondrial swelling and vacuolization. Mitochondrial precipitate, both crystalline and amorphous in form, was observed and presumed to be calcium phosphate, either alone or mixed with calcium carbonate. The possibility that the morphological changes observed might indicate subcellular loci of specific ion permeability is discussed. A correlation of the known kinetic behavior of sodium and calcium ions in mammalian myocardium with the ultrastructural alterations produced is suggested. PMID:5650905

  2. Interrelationships of ultrastructure and function in the microvasculature of normal and ischaemic myocardium.

    PubMed

    Gavin, J B; Maxwell, L; Sage, M D

    1991-12-01

    This paper reviews various methods involving electron microscopy that have been used to investigate the ultrastructure of the vasculature of the normal and diseased heart. Whereas scanning electron microscopy is more commonly employed to record surface topography, it can be used to examine freeze-fracture planes within the myocardium and, using heavy-metal staining and back-scattered electron imaging, to examine large 2-mu-thick resin-embedded sections through the heart. The latter technique allows the comparison of structural alterations across the wall of the heart and thus accurate definition of the transmural progression of pathological processes. Transmission electron microscopy can then be used to provide more detailed information from precisely localised regions. Human myocardium can be usefully studied up to 12 hours post-mortem provided that suitable control material is included. Intravascular tracers including low-viscosity resin and nuclear track emulsion can be used to determine whether or not particular vessels allow flow at the time of fixation, and thus changes in the pattern of flow through the microvasculature due to ischaemia and reperfusion can be quantified and defined. Particular care is required in the fixation of ischaemic tissues because oxygen dissolved in the fixative can lead to the rapid formation of oxygen-free radicals on contact with the tissue. This produces artefactual reoxygenation damage characterised by membrane disruption and cell and organelle swelling, which has previously been attributed to ischaemic injury per se. Bubbling glutaraldehyde with nitrogen substantially reduces this artefact.

  3. Effects of inhibition of. beta. -oxidation on tissue kinetics of C-11 palmitate in normal myocardium

    SciTech Connect

    Wijns, W.; Schwaiger, M.; Huang, S.C.; Selin, C.; Grover-McKay, M.; Hansen, H.; Phelps, M.; Schelbert, H.R.

    1985-05-01

    C-11 palmitate (CPA) clears from myocardium biexponentially. The late slow tissue clearance curve component is thought to represent tracer deposited in the endogenous lipid pool. The early rapid component is thought to be related to oxidation of CPA. The nature of the curve components can be clarified by specific inhibition of individual metabolic steps, e.g., ..beta..-oxidation. Therefore, 11 dogs were studied at control and again after inhibition of carnitine acyltransferase I with iv. tetradecylglycidic acid (TDGA; 10 mg/kg). CPA was injected into the coronary circulation. Myocardial time activity curves (TAC) were analyzed by least square fitting. After TDGA, the late slow phase was unchanged (RS=32 +- 9%; T=336 +- 146 min) but the early rapid phase was reduced (RS=18 +- 8%; T=2.9 +- 1.4 min) while 50 +- 9% of extracted CPA diffused back (T=10.8 +- 3.6 sec). Thus, inhibition of ..beta..-oxidation shifted substrate usage from FFA to carbohydrates, had no effect on esterification of CPA but enhanced its back diffusion from myocardium. As discussed in this paper the decline of the early rapid phase indicates its relationship to CPA oxidation.

  4. Effects of allocryptopine on outward potassium current and slow delayed rectifier potassium current in rabbit myocardium

    PubMed Central

    Fu, Yi-Cheng; Zhang, Yu; Tian, Liu-Yang; Li, Nan; Chen, Xi; Cai, Zhong-Qi; Zhu, Chao; Li, Yang

    2016-01-01

    Objective Allocryptopine (ALL) is an effective alkaloid of Corydalis decumbens (Thunb.) Pers. Papaveraceae and has proved to be anti-arrhythmic. The purpose of our study is to investigate the effects of ALL on transmural repolarizing ionic ingredients of outward potassium current (Ito) and slow delayed rectifier potassium current (IKs). Methods The monophasic action potential (MAP) technique was used to record the MAP duration of the epicardium (Epi), myocardium (M) and endocardium (Endo) of the rabbit heart and the whole cell patch clamp was used to record Ito and IKs in cardiomyocytes of Epi, M and Endo layers that were isolated from rabbit ventricles. Results The effects of ALL on MAP of Epi, M and Endo layers were disequilibrium. ALL could effectively reduce the transmural dispersion of repolarization (TDR) in rabbit transmural ventricular wall. ALL decreased the current densities of Ito and IKs in a voltage and concentration dependent way and narrowed the repolarizing differences among three layers. The analysis of gating kinetics showed ALL accelerated the channel activation of Ito in M layers and partly inhibit the channel openings of Ito in Epi, M and Endo cells. On the other hand, ALL mainly slowed channel deactivation of IKs channel in Epi and Endo layers without affecting its activation. Conclusions Our study gives partially explanation about the mechanisms of transmural inhibition of Ito and IKs channels by ALL in rabbit myocardium. These findings provide novel perspective regarding the anti-arrhythmogenesis application of ALL in clinical settings. PMID:27403141

  5. Anisotropic engineered heart tissue made from laser-cut decellularized myocardium

    PubMed Central

    Schwan, Jonas; Kwaczala, Andrea T.; Ryan, Thomas J.; Bartulos, Oscar; Ren, Yongming; Sewanan, Lorenzo R.; Morris, Aaron H.; Jacoby, Daniel L.; Qyang, Yibing; Campbell, Stuart G.

    2016-01-01

    We have developed an engineered heart tissue (EHT) system that uses laser-cut sheets of decellularized myocardium as scaffolds. This material enables formation of thin muscle strips whose biomechanical characteristics are easily measured and manipulated. To create EHTs, sections of porcine myocardium were laser-cut into ribbon-like shapes, decellularized, and mounted in specialized clips for seeding and culture. Scaffolds were first tested by seeding with neonatal rat ventricular myocytes. EHTs beat synchronously by day five and exhibited robust length-dependent activation by day 21. Fiber orientation within the scaffold affected peak twitch stress, demonstrating its ability to guide cells toward physiologic contractile anisotropy. Scaffold anisotropy also made it possible to probe cellular responses to stretch as a function of fiber angle. Stretch that was aligned with the fiber direction increased expression of brain natriuretic peptide, but off-axis stretches (causing fiber shear) did not. The method also produced robust EHTs from cardiomyocytes derived from human embryonic stem cells and induced pluripotent stem cells (hiPSC). hiPSC-EHTs achieved maximum peak stress of 6.5 mN/mm2 and twitch kinetics approaching reported values from adult human trabeculae. We conclude that laser-cut EHTs are a viable platform for novel mechanotransduction experiments and characterizing the biomechanical function of patient-derived cardiomyoctyes. PMID:27572147

  6. Impact of decellularization on porcine myocardium as scaffold for tissue engineered heart tissue.

    PubMed

    Ye, Xiaofeng; Wang, Haozhe; Gong, Wenhui; Li, Shen; Li, Haiqing; Wang, Zhe; Zhao, Qiang

    2016-04-01

    Decellularized myocardium has been proposed to construct tissue engineered heart tissue, providing the advantage of natural extracellular architecture. Various decellularization protocols have been developed, but the impact of individual decellularization reagent in the protocol remains unclear. The aim of this study is to evaluate the structural impact of three commonly used decellularization reagents on the porcine myocardium. We decellularized porcine heart tissue with trypsin, Triton X-100 or SDS, and analyzed the morphological characteristics of the remaining tissue by SEM, AFM and two-photon LSM. We further recellularized the scaffold with rat myocardial fibroblasts and cardiomyocytes separately. According to the H&E staining and DNA quantification, SDS decellularized more efficiently in comparison to the other two reagents. Moreover, we found distinct surface microarchitecture differences among groups. The changed structure of tissue might result in varied proliferation myocardial fibroblasts and biophysical performance of the engineered heart tissue. This study demonstrated that the microstructure of decellularized porcine heart tissue vary with decellularization agents. Compared to trypsin and Triton X-100, SDS not only decellularized more efficiently but also preserved the biocompatible microstructure of ECM for recellularization.

  7. [The morphological changes in the myocardium associated with the craniocerebral injury].

    PubMed

    Boyarinov, G A; Deryugina, A V; Zaitsev, R R; Yakovleva, E I; Nikol'sky, V O; Boyarinova, L V; Galkina, M V

    2017-01-01

    The objective of the present study was to evaluate the structural changes in the capillaries, arterioles, venules, and cardiomyocytes in the myocardium of the rats following the craniocerebral injury (CCI). Eighteen non-pedigree white female rats with the craniocerebral injury were used as the CCI model. All the animals were given an intraperitoneal injection of sodium thiopental (100 mg/kg b.w.) within 3, 7, and 12 days after the injury. The heart was removed after thoracotomy and the myocardial tissue was examined with the light and electron microscopes. It was shown that the rats with the craniocerebral injury developed well apparent changes in the myocardial tissue during the early post-traumatic period that affected not only the blood vessels themselves (capillaries, arterioles, venules) but also the intra- and extravascular structures. Changes in the microcirculatory system included damages to the mitochondria, myofibrils, cell nuclei, sarcoplasmic reticulum, and cardiomyocytes. It is concluded that the morphological changes in the myocardium of the animals associated with the craniocerebral injury can induce the development of functional disorders in the cardiovascular system during the early post-traumatic period.

  8. Pathways for ischemic cytoprotection: Role of sirtuins in caloric restriction, resveratrol, and ischemic preconditioning

    PubMed Central

    Morris, Kahlilia C; Lin, Hung Wen; Thompson, John W; Perez-Pinzon, Miguel A

    2011-01-01

    Caloric restriction (CR), resveratrol, and ischemic preconditioning (IPC) have been shown to promote protection against ischemic injury in the heart and brain, as well as in other tissues. The activity of sirtuins, which are enzymes that modulate diverse biologic processes, seems to be vital in the ability of these therapeutic modalities to prevent against cellular dysfunction and death. The protective mechanisms of the yeast Sir2 and the mammalian homolog sirtuin 1 have been extensively studied, but the involvement of other sirtuins in ischemic protection is not yet clear. We examine the roles of mammalian sirtuins in modulating protective pathways against oxidative stress, energy depletion, excitotoxicity, inflammation, DNA damage, and apoptosis. Although many of these sirtuins have not been directly implicated in ischemic protection, they may have unique roles in enhancing function and preventing against stress-mediated cellular damage and death. This review will include in-depth analyses of the roles of CR, resveratrol, and IPC in activating sirtuins and in mediating protection against ischemic damage in the heart and brain. PMID:21224864

  9. Cost and Outcome in Pediatric Ischemic Stroke.

    PubMed

    Hamilton, William; Huang, Haijuan; Seiber, Eric; Lo, Warren

    2015-10-01

    The cost of childhood stroke receives little notice. The authors examined potential drivers of cost and outcome to test whether (1) neonatal strokes cost less than childhood strokes, (2) associated diseases influence cost, (3) arterial ischemic stroke is more costly than sinovenous thrombosis, and (4) cost correlates with outcome. The authors reviewed records of 111 children who sustained arterial ischemic stroke or sinovenous thrombosis between 2005 and 2010 to identify costs for the following year. They assessed outcomes in 46 with the Recovery and Recurrence Questionnaire and the Pediatric Quality of Life Inventory. Neonatal strokes cost less than childhood stroke. Strokes associated with congenital heart disease or vasculopathy cost the most, while perinatal or idiopathic strokes cost the least. Higher costs are correlated with worse impairment and poorer quality of life. Stroke etiology significantly influences the cost of pediatric stroke. Future cost-benefit studies must consider etiology when estimating the incremental costs associated with stroke.

  10. Aspirin resistant patients with recent ischemic stroke.

    PubMed

    Castilla-Guerra, L; Navas-Alcántara, M S; Fernández-Moreno, M C

    2014-04-01

    Some patients with a recent ischemic stroke who are being treated with aspirin as an antiaggregant suffer a new ischemic stroke. These patients (15-25%) have been called unresponsive to aspirin or aspirin resistant. The aspirin-resistant patients have a four-time greater risk of suffering a stroke. Furthermore, these strokes are generally more severe, with increased infarct volume and greater risk of recurrence. There is currently no ideal laboratory test to detect the resistance to the antiaggregant effect of aspirin. The study of resistance to aspirin would only be indicated in selected cases. In these patients, one should first rule out any "pseudo-resistance" to aspirin (lack of compliance, concomitant treatments that interfere with the action of the aspirin).

  11. Isolated naratriptan-associated ischemic colitis

    PubMed Central

    Nissan, George; Chaudhry, Priyanka; Rangasamy, Priya; Mudrovich, Steven

    2016-01-01

    We report a 41-year-old woman who developed histology- and colonoscopy-proven ischemic colitis with the use of naratriptan not exceeding the maximum 2 doses a day and 3 days per week and without a known medical or cardiovascular history. By exclusion of other causes of colonic ischemia, naratriptan was considered the sole causal agent. Discontinuation of naratriptan resulted in a complete clinical recovery. To date, our patient is the youngest known patient to develop ischemic colitis on isolated naratriptan in the setting of no known medical risk factors or predisposing medical condition. Even though triptans are commonly used for the abortive treatment of migraine headaches, such a reported side effect is rare; however, careful assessment and individual patient-based treatment is advised. PMID:27695179

  12. Molecular chaperones and hypoxic-ischemic encephalopathy

    PubMed Central

    Hua, Cong; Ju, Wei-na; Jin, Hang; Sun, Xin; Zhao, Gang

    2017-01-01

    Hypoxic-ischemic encephalopathy (HIE) is a disease that occurs when the brain is subjected to hypoxia, resulting in neuronal death and neurological deficits, with a poor prognosis. The mechanisms underlying hypoxic-ischemic brain injury include excitatory amino acid release, cellular proteolysis, reactive oxygen species generation, nitric oxide synthesis, and inflammation. The molecular and cellular changes in HIE include protein misfolding, aggregation, and destruction of organelles. The apoptotic pathways activated by ischemia and hypoxia include the mitochondrial pathway, the extrinsic Fas receptor pathway, and the endoplasmic reticulum stress-induced pathway. Numerous treatments for hypoxic-ischemic brain injury caused by HIE have been developed over the last half century. Hypothermia, xenon gas treatment, the use of melatonin and erythropoietin, and hypoxic-ischemic preconditioning have proven effective in HIE patients. Molecular chaperones are proteins ubiquitously present in both prokaryotes and eukaryotes. A large number of molecular chaperones are induced after brain ischemia and hypoxia, among which the heat shock proteins are the most important. Heat shock proteins not only maintain protein homeostasis; they also exert anti-apoptotic effects. Heat shock proteins maintain protein homeostasis by helping to transport proteins to their target destinations, assisting in the proper folding of newly synthesized polypeptides, regulating the degradation of misfolded proteins, inhibiting the aggregation of proteins, and by controlling the refolding of misfolded proteins. In addition, heat shock proteins exert anti-apoptotic effects by interacting with various signaling pathways to block the activation of downstream effectors in numerous apoptotic pathways, including the intrinsic pathway, the endoplasmic reticulum-stress mediated pathway and the extrinsic Fas receptor pathway. Molecular chaperones play a key role in neuroprotection in HIE. In this review, we

  13. Hypoxic Ischemic Encephalopathy in the Term Infant

    PubMed Central

    Fatemi, Ali; Wilson, Mary Ann; Johnston, Michael V.

    2010-01-01

    Synopsis Hypoxia-ischemia in the perinatal period is an important cause of cerebral palsy and associated disabilities in children. There has been significant research progress in hypoxic-ischemic encephalopathy over the last two decades and many new molecular mechanisms have been identified. Despite all these advances, therapeutic interventions are still limited. In this review paper, we discuss a number of molecular pathways involved in hypoxia-ischemia, and potential therapeutic targets. PMID:19944838

  14. Hydrophilic Polymer-associated Ischemic Enterocolitis.

    PubMed

    Chavez, Jesus A; Chen, Wei; Frankel, Wendy L; Arnold, Christina A

    2017-02-01

    Hydrophilic polymer coating of medical devices serves to lubricate the device and prevent device-related complications. The coating can be mechanically disrupted and result in downstream injury via presumed thromboembolism. This process has been reported in the brain, heart, lung, and skin, and has been replicated through animal studies and in vitro histologic processing of the polymer coating. We report the first description of hydrophilic polymer-associated ischemic enterocolitis in a series of 7 specimens (small bowel=2, colon=4, aortic thrombus=1) from 3 patients. We report a 4% incidence among all patients with an ischemic bowel resection between April 29, 2014 and August 8, 2016. All patients developed bowel ischemia within 1 day of aortic repair, and all bowel resection specimens showed polymers, mainly in the submucosal vessels in areas of extensive ischemia. The polymers appeared as basophilic, intravascular, serpiginous structures. In a patient who developed acute paralysis after the aortic repair, identical polymers were identified in the aortic thrombus and the ischemic bowel segment. We demonstrate that the polymers display an altered morphology over time and with various graft types, and that the degrading polymers are associated with a foreign body giant cell reaction. Special stains can aid in diagnosis, with the polymers turquoise on a colloidal iron stain, pink on von Kossa and mucicarmine stains, and pale blue on trichrome. Clinical follow-up was available up to 115 weeks: 1 patient died, and 2 are alive and well. In summary, we report a new diagnostic entity to be considered in the differential diagnosis of iatrogenic ischemic injuries in the gastrointestinal tract. Awareness of this entity is important to elucidate the cause of ischemia and to prevent misdiagnosis of the polymers and their associated giant cell reaction as a parasitic infection, granulomatous vasculitis, sarcoidosis, and idiopathic inflammatory bowel disease.

  15. Ischemic Colitis in an Endurance Runner

    PubMed Central

    Grames, Chase; Berry-Cabán, Cristóbal S.

    2012-01-01

    A 20-year-old female running the Marine Corps Marathon developed diarrhea at mile 12. After finishing the race she noted that she was covered in bloody stool. A local emergency department suspected ischemic colitis. After discharge, her primary care physician instructed her to discontinue the use of all nonsteroidal anti-inflammatory drugs. Her symptoms resolved and she returned to running without any complications. This paper describes the pathophysiology, diagnostic approach, and management options. PMID:23091744

  16. Intracellular route of canine parvovirus entry.

    PubMed

    Vihinen-Ranta, M; Kalela, A; Mäkinen, P; Kakkola, L; Marjomäki, V; Vuento, M

    1998-01-01

    The present study was designed to investigate the endocytic pathway involved in canine parvovirus (CPV) infection. Reduced temperature (18 degrees C) or the microtubule-depolymerizing drug nocodazole was found to inhibit productive infection of canine A72 cells by CPV and caused CPV to be retained in cytoplasmic vesicles as indicated by immunofluorescence microscopy. Consistent with previously published results, these data indicate that CPV enters a host cell via an endocytic route and further suggest that microtubule-dependent delivery of CPV to late endosomes is required for productive infection. Cytoplasmic microinjection of CPV particles was used to circumvent the endocytosis and membrane fusion steps in the entry process. Microinjection experiments showed that CPV particles which were injected directly into the cytoplasm, thus avoiding the endocytic pathway, were unable to initiate progeny virus production. CPV treated at pH 5.0 prior to microinjection was unable to initiate virus production, showing that factors of the endocytic route other than low pH are necessary for the initiation of infection by CPV.

  17. Intracellular Route of Canine Parvovirus Entry

    PubMed Central

    Vihinen-Ranta, Maija; Kalela, Anne; Mäkinen, Päivi; Kakkola, Laura; Marjomäki, Varpu; Vuento, Matti

    1998-01-01

    The present study was designed to investigate the endocytic pathway involved in canine parvovirus (CPV) infection. Reduced temperature (18°C) or the microtubule-depolymerizing drug nocodazole was found to inhibit productive infection of canine A72 cells by CPV and caused CPV to be retained in cytoplasmic vesicles as indicated by immunofluorescence microscopy. Consistent with previously published results, these data indicate that CPV enters a host cell via an endocytic route and further suggest that microtubule-dependent delivery of CPV to late endosomes is required for productive infection. Cytoplasmic microinjection of CPV particles was used to circumvent the endocytosis and membrane fusion steps in the entry process. Microinjection experiments showed that CPV particles which were injected directly into the cytoplasm, thus avoiding the endocytic pathway, were unable to initiate progeny virus production. CPV treated at pH 5.0 prior to microinjection was unable to initiate virus production, showing that factors of the endocytic route other than low pH are necessary for the initiation of infection by CPV. PMID:9420290

  18. Expression of Bcl-2 in canine osteosarcoma

    PubMed Central

    Piro, F.; Leonardi, L.

    2015-01-01

    Osteosarcoma (OS) is the most common primary malignancy of bone. It is responsible for 80-85% of the primary bone tumors affecting dogs and it is characterized by aggressive and invasive behavior, with a high metastatic potential. Several studies on cancer and related tumorigenesis, show an involvement of the mechanisms of programmed cell death and cell survival. Many signals seem to be involved in the related mechanism of autophagy and in particular, our interest is focused on the expression of a family of Bcl-2 that seems to be involved either in the control of biomolecular mechanisms like autophagy and apoptosis. In this study we investigated the expression of Bcl-2 in different cases of spontaneous canine osteosarcoma and the related preliminary results are described. We found Bcl-2 activity was increased in OS tissue compared to normal bone tissue. These results suggested that Bcl-2 activity may play an important role in the formation of OS and as a diagnostic for neoplastic activity. However, further research is needed to confirm the role of Bcl-2 activity in OS in canines. PMID:26623359

  19. Canine Models for Copper Homeostasis Disorders

    PubMed Central

    Wu, Xiaoyan; Leegwater, Peter A. J.; Fieten, Hille

    2016-01-01

    Copper is an essential trace nutrient metal involved in a multitude of cellular processes. Hereditary defects in copper metabolism result in disorders with a severe clinical course such as Wilson disease and Menkes disease. In Wilson disease, copper accumulation leads to liver cirrhosis and neurological impairments. A lack in genotype-phenotype correlation in Wilson disease points toward the influence of environmental factors or modifying genes. In a number of Non-Wilsonian forms of copper metabolism, the underlying genetic defects remain elusive. Several pure bred dog populations are affected with copper-associated hepatitis showing similarities to human copper metabolism disorders. Gene-mapping studies in these populations offer the opportunity to discover new genes involved in copper metabolism. Furthermore, due to the relatively large body size and long life-span of dogs they are excellent models for development of new treatment strategies. One example is the recent use of canine organoids for disease modeling and gene therapy of copper storage disease. This review addresses the opportunities offered by canine genetics for discovery of genes involved in copper metabolism disorders. Further, possibilities for the use of dogs in development of new treatment modalities for copper storage disorders, including gene repair in patient-derived hepatic organoids, are highlighted. PMID:26861285

  20. Canine Models for Copper Homeostasis Disorders.

    PubMed

    Wu, Xiaoyan; Leegwater, Peter A J; Fieten, Hille

    2016-02-04

    Copper is an essential trace nutrient metal involved in a multitude of cellular processes. Hereditary defects in copper metabolism result in disorders with a severe clinical course such as Wilson disease and Menkes disease. In Wilson disease, copper accumulation leads to liver cirrhosis and neurological impairments. A lack in genotype-phenotype correlation in Wilson disease points toward the influence of environmental factors or modifying genes. In a number of Non-Wilsonian forms of copper metabolism, the underlying genetic defects remain elusive. Several pure bred dog populations are affected with copper-associated hepatitis showing similarities to human copper metabolism disorders. Gene-mapping studies in these populations offer the opportunity to discover new genes involved in copper metabolism. Furthermore, due to the relatively large body size and long life-span of dogs they are excellent models for development of new treatment strategies. One example is the recent use of canine organoids for disease modeling and gene therapy of copper storage disease. This review addresses the opportunities offered by canine genetics for discovery of genes involved in copper metabolism disorders. Further, possibilities for the use of dogs in development of new treatment modalities for copper storage disorders, including gene repair in patient-derived hepatic organoids, are highlighted.

  1. White matter injury in ischemic stroke.

    PubMed

    Wang, Yuan; Liu, Gang; Hong, Dandan; Chen, Fenghua; Ji, Xunming; Cao, Guodong

    2016-06-01

    Stroke is one of the major causes of disability and mortality worldwide. It is well known that ischemic stroke can cause gray matter injury. However, stroke also elicits profound white matter injury, a risk factor for higher stroke incidence and poor neurological outcomes. The majority of damage caused by stroke is located in subcortical regions and, remarkably, white matter occupies nearly half of the average infarct volume. Indeed, white matter is exquisitely vulnerable to ischemia and is often injured more severely than gray matter. Clinical symptoms related to white matter injury include cognitive dysfunction, emotional disorders, sensorimotor impairments, as well as urinary incontinence and pain, all of which are closely associated with destruction and remodeling of white matter connectivity. White matter injury can be noninvasively detected by MRI, which provides a three-dimensional assessment of its morphology, metabolism, and function. There is an urgent need for novel white matter therapies, as currently available strategies are limited to preclinical animal studies. Optimal protection against ischemic stroke will need to encompass the fortification of both gray and white matter. In this review, we discuss white matter injury after ischemic stroke, focusing on clinical features and tools, such as imaging, manifestation, and potential treatments. We also briefly discuss the pathophysiology of WMI and future research directions.

  2. Neurovascular Regulation in the Ischemic Brain

    PubMed Central

    Jackman, Katherine

    2015-01-01

    Abstract Significance: The brain has high energetic requirements and is therefore highly dependent on adequate cerebral blood supply. To compensate for dangerous fluctuations in cerebral perfusion, the circulation of the brain has evolved intrinsic safeguarding measures. Recent Advances and Critical Issues: The vascular network of the brain incorporates a high degree of redundancy, allowing the redirection and redistribution of blood flow in the event of vascular occlusion. Furthermore, active responses such as cerebral autoregulation, which acts to maintain constant cerebral blood flow in response to changing blood pressure, and functional hyperemia, which couples blood supply with synaptic activity, allow the brain to maintain adequate cerebral perfusion in the face of varying supply or demand. In the presence of stroke risk factors, such as hypertension and diabetes, these protective processes are impaired and the susceptibility of the brain to ischemic injury is increased. One potential mechanism for the increased injury is that collateral flow arising from the normally perfused brain and supplying blood flow to the ischemic region is suppressed, resulting in more severe ischemia. Future Directions: Approaches to support collateral flow may ameliorate the outcome of focal cerebral ischemia by rescuing cerebral perfusion in potentially viable regions of the ischemic territory. Antioxid. Redox Signal. 22, 149–160. PMID:24328757

  3. [Ischemic stroke in the young adult].

    PubMed

    Calvet, D

    2016-01-01

    Ischemic stroke is not rare in young adults since one in ten stroke patients are less than 50 years old. This incidence increased over the past last years, mainly due to the rise in the prevalence of traditional vascular risk factors in this sub-group of age but also of illegal drug use. Even though both survival and functional outcome of young stroke patients are better than those observed in older patients, socio-economic and quality of life consequences make this disease a main objective in terms of primary and secondary prevention. Identifying the cause of ischemic stroke in young adults is of major importance to prevent stroke recurrence. However, given the wide variety of potential underlying causes, the etiologic work-up of stroke in young adults requires a different approach from that in the elderly. In this context, a sequential diagnostic work-up is needed in order to optimize the yield of diagnostic tests, to reduce their cost and risks for the patient. Arterial dissection is the most frequent cause of stroke in young adults but other less frequent causes are numerous. Despite a comprehensive work-up, about one third of cases remains unexplained leading to the diagnosis of cryptogenic ischemic stroke.

  4. Applicability of biomarkers in ischemic stroke.

    PubMed

    Castellanos, Mar; Serena, Joaquín

    2007-01-01

    Cerebral ischemia results in the activation of a cascade of molecular events as a result of which several substances with the potential characteristics of biomarkers are released into the peripheral blood. Although still in the research phase, the analysis of these biomarkers in the serum has proved to be useful for stroke diagnosis, as well as for the prediction of the evolution of the ischemic lesion and the clinical prognosis. In fact, the feasibility and applicability of a panel of biomarkers for the diagnosis of stroke has recently been tested. Biomarkers of excitotoxicity, inflammation and oxidative stress have been demonstrated as being useful in the prediction of ischemic lesion enlargement and secondary neurological deterioration. On the other hand, biomarkers of endothelial damage have been shown to be especially helpful in the prediction of hemorrhagic transformation of the ischemic lesion, both spontaneously and after the administration of thrombolytic therapy, as well as in the prediction of brain edema with the secondary development of malignant middle-cerebral-artery infarction. Moreover, coagulation and fibrinolytic-cascade markers have been reported as being correlated with the recanalization rate after the administration of thrombolysis, and they might therefore be useful in estimating the effectiveness of thrombolytic therapy. However, for these biomarkers to become applicable to routine clinical practice, faster tests to perform the analyses are required and further studies must be undertaken to validate and generalize the results.

  5. Canine mammary tumour cell lines established in vitro.

    PubMed

    Hellmén, E

    1993-01-01

    Mammary tumours are the most common tumours in the female dog. The tumours have a complex histology and exist in epithelial, mixed and mesenchymal forms. To study the biology of canine mammary tumours, five cell lines have been established and characterized. The results indicate that canine mammary tumours might be derived from mammary stem cells and that the tumour growth is independent of oestrogens. The established canine mammary tumour cell lines will be valuable tools in further studies of the histogenesis and pathogenesis of these tumours.

  6. Intranasal vaccine trial for canine infectious tracheobronchitis (kennel cough).

    PubMed

    Glickman, L T; Appel, M J

    1981-08-01

    Two field trials were conducted during periods of endemic (summer) and epizootic (winter) canine infectious tracheobronchitis activity to evaluate the efficacy of three intranasal vaccines in a closed commercial beagle breeding kennel. A trivalent vaccine containing Bordetella bronchiseptica, canine parainfluenza, and canine adenovirus-2 was administered at 3 weeks of age. The vaccine was 71.2% and 81.8% effective in decreasing the incidence of coughing during the winter and summer trials, respectively. The number of deaths was lower in each of the vaccine groups than in the placebo groups. No adverse reactions were observed with any of the intranasal vaccines.

  7. Cardioprotection by remote ischemic conditioning: Mechanisms and clinical evidences

    PubMed Central

    Aimo, Alberto; Borrelli, Chiara; Giannoni, Alberto; Pastormerlo, Luigi Emilio; Barison, Andrea; Mirizzi, Gianluca; Emdin, Michele; Passino, Claudio

    2015-01-01

    In remote ischemic conditioning (RIC), several cycles of ischemia and reperfusion render distant organ and tissues more resistant to the ischemia-reperfusion injury. The intermittent ischemia can be applied before the ischemic insult in the target site (remote ischemic preconditioning), during the ischemic insult (remote ischemic perconditioning) or at the onset of reperfusion (remote ischemic postconditioning). The mechanisms of RIC have not been completely defined yet; however, these mechanisms must be represented by the release of humoral mediators and/or the activation of a neural reflex. RIC has been discovered in the heart, and has been arising great enthusiasm in the cardiovascular field. Its efficacy has been evaluated in many clinical trials, which provided controversial results. Our incomplete comprehension of the mechanisms underlying the RIC could be impairing the design of clinical trials and the interpretation of their results. In the present review we summarize current knowledge about RIC pathophysiology and the data about its cardioprotective efficacy. PMID:26516416

  8. Kinetics of canine dental calculus crystallization: an in vitro study on the influence of inorganic components of canine saliva.

    PubMed

    Borah, Ballav M; Halter, Timothy J; Xie, Baoquan; Henneman, Zachary J; Siudzinski, Thomas R; Harris, Stephen; Elliott, Matthew; Nancollas, George H

    2014-07-01

    This work identifies carbonated hydroxyapatite (CAP) as the primary component of canine dental calculus, and corrects the long held belief that canine dental calculus is primarily CaCO3 (calcite). CAP is known to be the principal crystalline component of human dental calculus, suggesting that there are previously unknown similarities in the calcification that occurs in these two unique oral environments. In vitro kinetic experiments mimicking the inorganic components of canine saliva have examined the mechanisms of dental calculus formation. The solutions were prepared so as to mimic the inorganic components of canine saliva; phosphate, carbonate, and magnesium ion concentrations were varied individually to investigate the roll of these ions in controlling the nature of the phases that is nucleated. To date, the inorganic components of the canine oral systems have not been investigated at concentrations that mimic those in vivo. The mineral composition of the synthetic calculi grown under these conditions closely resembled samples excised from canines. This finding adds new information about calculus formation in humans and canines, and their sensitivity to chemicals used to treat these conditions.

  9. Canine Visceral Leishmaniasis in Wild Canines (Fox, Jackal, and Wolf) in Northeastern Iran Using Parasitological, Serological, and Molecular Methods

    PubMed Central

    Mohebali, Mehdi; Arzamani, Kourosh; Zarei, Zabiholah; Akhoundi, Behnaz; Hajjaran, Homa; Raeghi, Saber; Heidari, Zahra; Motavalli-Haghi, Seyed Mousa; Elikaee, Samira; Mousazadeh-Mojarrad, Ahmad; Kakoei, Zahra

    2016-01-01

    Background: Although many studies had been conducted on various aspects of canine visceral leishmaniasis (CVL) in domestic dogs in the endemic areas of Iran, investigations on CVL in wild canines are rare. Methods: This is a cross-sectional study was conducted from December 2012 to 2013 in northeast of Iran where human VL is endemic. Wild canines were trapped around the areas where human VL cases had been previously identified. Wild canines were collected and examined both clinically and serologically using direct agglutination test (DAT). Microscopically examinations were performed in all the seropositive wild canines for the presence of the amastigote form of Leishmania spp. Some Leishmania sp. which had been isolated from the spleens of wild canines, were examined analyzed by conventional PCR and sequencing techniques using α-tubulin and GAPDH genes. Results: Altogether, 84 wild canines including foxes (Vulpes vulpes, n=21), Jackals (Canis aureus, n=60) and wolves (Canis lupus, n=3) were collected. Four foxes and seven jackals showed anti-Leishmania infantum antibodies with titers of 1:320–1:20480 in DAT. Furthermore, one fox and one jackal were parasitologically (microscopy and culture) positive and L. infantum was confirmed by sequence analysis. Conclusion: The present study showed that sylvatic cycle of L. infantum had been established in the studied endemic areas of VL in northeastern Iran. PMID:28032106

  10. Arterial Spin Label Imaging of Acute Ischemic Stroke and Transient Ischemic Attack

    PubMed Central

    Zaharchuk, Greg

    2011-01-01

    Since acute ischemic stroke and transient ischemic attack (TIA) are fundamentally disruptions of brain hemodynamics, neuroimaging of brain perfusion might be expected to be of clinical utility. Recently, a noncontrast method of measuring CBF using arterial spin labeling (ASL) has become feasible in the clinical setting. It has advantages when compared to dynamic susceptibility contrast (DSC) bolus contrast perfusion-weighted imaging (PWI) that include lack of exposure to gadolinium-based contrast materials, improved quantitation, and decreased sensitivity to susceptibility artifacts and motion. Drawbacks of ASL include reduced signal-to-noise (SNR) and high sensitivity to arterial transit delays. While deleterious for quantitative perfusion measurements, the sensitivity of ASL to late arriving blood can be beneficial to visualize collateral flow. This chapter will discuss ASL imaging findings in patients presenting with acute ischemic stroke and TIA, focusing on typical appearances, common artifacts, and comparisons with bolus contrast PWI. PMID:21640300

  11. Gene expression profiling of human hibernating myocardium: increased expression of B-type natriuretic peptide and proenkephalin in hypocontractile vs normally-contracting regions of the heart.

    PubMed

    Prasad, Sanjay K; Clerk, Angela; Cullingford, Timothy E; Chen, Alexander W Y; Kemp, Timothy J; Cannell, Timothy M; Cowie, Martin R; Petrou, Mario

    2008-12-01

    A greater understanding of the molecular basis of hibernating myocardium may assist in identifying those patients who would most benefit from revascularization. Paired heart biopsies were taken from hypocontractile and normally-contracting myocardium (identified by cardiovascular magnetic resonance) from 6 patients with chronic stable angina scheduled for bypass grafting. Gene expression profiles of hypocontractile and normally-contracting samples were compared using Affymetrix microarrays. The data for patients with confirmed hibernating myocardium were analysed separately and a different, though overlapping, set (up to 380) of genes was identified which may constitute a molecular fingerprint for hibernating myocardium. The expression of B-type natriuretic peptide (BNP) was increased in hypocontractile relative to normally-contracting myocardium. The expression of BNP correlated most closely with the expression of proenkephalin and follistatin 3, which may constitute additional heart failure markers. Our data illustrate differential gene expression in hypocontractile and/hibernating myocardium relative to normally-contracting myocardium within individual human hearts. Changes in expression of these genes, including increased relative expression of natriuretic and other factors, may constitute a molecular signature for hypocontractile and/or hibernating myocardium.

  12. Clinical and serological response of wild dogs (Lycaon pictus) to vaccination against canine distemper, canine parvovirus infection and rabies.

    PubMed

    van Heerden, J; Bingham, J; van Vuuren, M; Burroughs, R E J; Stylianides, E

    2002-03-01

    Wild dogs Lycaon pictuis (n = 8) were vaccinated 4 times against canine distemper (n = 8) (initially with inactivated and subsequently with live attenuated strains of canine distemper) and canine parvovirus infection (n = 8) over a period of 360 days. Four of the wild dogs were also vaccinated 3 times against rabies using a live oral vaccine and 4 with an inactivated parenteral vaccine. Commercially-available canine distemper, canine parvovirus and parenteral rabies vaccines, intended for use in domestic dogs, were used. None of the vaccinated dogs showed any untoward clinical signs. The inactivated canine distemper vaccine did not result in seroconversion whereas the attenuated live vaccine resulted in seroconversion in all wild dogs. Presumably protective concentrations of antibodies to canine distemper virus were present in all wild dogs for at least 451 days. Canine parvovirus haemagglutination inhibition titres were present in all wild dogs prior to the administration of vaccine and protective concentrations persisted for at least 451 days. Vaccination against parvovirus infection resulted in a temporary increase in canine parvovirus haemagglutination inhibition titres in most dogs. Administration of both inactivated parenteral and live oral rabies vaccine initially resulted in seroconversion in 7 of 8 dogs. These titres, however, dropped to very low concentrations within 100 days. Booster administrations resulted in increased antibody concentrations in all dogs. It was concluded that the vaccines were safe to use in healthy subadult wild dogs and that a vaccination protocol in free-ranging wild dogs should at least incorporate booster vaccinations against rabies 3-6 months after the first inoculation.

  13. New Treatments for Nonarteritic Anterior Ischemic Optic Neuropathy.

    PubMed

    Foroozan, Rod

    2017-02-01

    Despite increasing knowledge about the risk factors and clinical findings of nonarteritic anterior ischemic optic neuropathy (NAION), the treatment of this optic neuropathy has remained limited and without clear evidence-based benefit. Historical treatments of NAION are reviewed, beginning with the Ischemic Optic Neuropathy Decompression Trial. More recent treatments are placed within the historical context and illustrate the need for evidence-based therapy for ischemic optic neuropathy.

  14. Effects of transient ischemia on nutrient flow and arteriovenous shunting in canine hindlimb.

    PubMed Central

    Kennedy, T J; Miller, S H; Nellis, S H; Buck, D; Flaim, S F; Graham, W P; Davis, T S

    1981-01-01

    A canine model was developed to simulate use of a pneumatic tourniquet in the clinical setting in order to study the acute and delayed effects of transient ischemia on limb and tissue blood flow, using radioactive microspheres and electromagnetic flow probes. Experimental femoral artery flow rose markedly after tourniquet ischemia, and remained significantly elevated for 24 hours (p less than 0.01). Blood flow to the rectus femoris and anterior tibial muscles rose significantly (p less than 0.05) immediately after tourniquet ischemia, and the latter remained significantly elevated at 24 hours (p less than 0.05). Blood flow to the skin of the experimental limbs was elevated significantly (p less than 0.05), immediately ater tourniquet ischemia, and at no other time. Blood flow to the nerves did not increase to its maximum until 15 minutes after tourniquet deflation, and by 24 hours was normal. Tibial and femoral marrow blood flow remained significantly lower in the experimental limb throughout the 24-hour period. Ater tourniquet ischemia (300 mmhg; 2 hours), greatly increased femoral artery flow was related to reactive hyperemia in skin, muscle, and nerve. Twenty-four hours after tourniquet deflation, there was a significant increase in femoral artery and anterior tibial muscle blood flow, and significant arteriovenous shunting from the experimental limb. These data suggest that the hemodynamic response to a transient ischemic injury is more prolonged and of greater magnitude than previously believed. PMID:7212787

  15. Regulated Synthesis and Functions of Laminin 5 in Polarized Madin-Darby Canine Kidney Epithelial Cells

    PubMed Central

    Mak, Grace Z.; Kavanaugh, Gina M.; Buschmann, Mary M.; Stickley, Shaun M.; Koch, Manuel; Goss, Kathleen Heppner; Waechter, Holly; Zuk, Anna

    2006-01-01

    Renal tubular epithelial cells synthesize laminin (LN)5 during regeneration of the epithelium after ischemic injury. LN5 is a truncated laminin isoform of particular importance in the epidermis, but it is also constitutively expressed in a number of other epithelia. To investigate the role of LN5 in morphogenesis of a simple renal epithelium, we examined the synthesis and function of LN5 in the spreading, proliferation, wound-edge migration, and apical–basal polarization of Madin-Darby canine kidney (MDCK) cells. MDCK cells synthesize LN5 only when subconfluent, and they degrade the existing LN5 matrix when confluent. Through the use of small-interfering RNA to knockdown the LN5 α3 subunit, we were able to demonstrate that LN5 is necessary for cell proliferation and efficient wound-edge migration, but not apical–basal polarization. Surprisingly, suppression of LN5 production caused cells to spread much more extensively than normal on uncoated surfaces, and exogenous keratinocyte LN5 was unable to rescue this phenotype. MDCK cells also synthesized laminin α5, a component of LN10, that independent studies suggest may form an assembled basal lamina important for polarization. Overall, our findings indicate that LN5 is likely to play an important role in regulating cell spreading, migration, and proliferation during reconstitution of a continuous epithelium. PMID:16775009

  16. Ischemic postconditioning protects against ischemic brain injury by up-regulation of acid-sensing ion channel 2a

    PubMed Central

    Duanmu, Wang-sheng; Cao, Liu; Chen, Jing-yu; Ge, Hong-fei; Hu, Rong; Feng, Hua

    2016-01-01

    Ischemic postconditioning renders brain tissue tolerant to brain ischemia, thereby alleviating ischemic brain injury. However, the exact mechanism of action is still unclear. In this study, a rat model of global brain ischemia was subjected to ischemic postconditioning treatment using the vessel occlusion method. After 2 hours of ischemia, the bilateral common carotid arteries were blocked immediately for 10 seconds and then perfused for 10 seconds. This procedure was repeated six times. Ischemic postconditioning was found to mitigate hippocampal CA1 neuronal damage in rats with brain ischemia, and up-regulate acid-sensing ion channel 2a expression at the mRNA and protein level. These findings suggest that ischemic postconditioning up-regulates acid-sensing ion channel 2a expression in the rat hippocampus after global brain ischemia, which promotes neuronal tolerance to ischemic brain injury. PMID:27212927

  17. Canine heartworm disease: a review and pilot study.

    PubMed

    Haddock, K C

    1987-01-01

    Canine heartworm disease is a mosquito vectored illness resulting from parasitization by the filariid worm Dirofilaria immitis. While presenting some danger to humans, the filariid has its greatest impact on the canine population. In recent years the disease has become established throughout much of the United States, perhaps as the result of diffusion from a suspected hearth in the southeastern coastal plain. While its distribution is known in general terms, much research remains to be done to assess the pattern of distribution as well as the impact of D. immitis on canine populations and their human owners for many locales. The present study provides a review of the literature on the parasite; on its distribution, particularly in the United States; and on the ecology of canine heartworm disease. A pilot study is presented which emphasizes the problems encountered in establishing a data base for observations on the disease at the local level.

  18. 41. overall view showing building 158, canine kennels on far ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    41. overall view showing building 158, canine kennels on far right, and building 156, Warhead Building, at far left, looking west - Nike Missile Battery MS-40, County Road No. 260, Farmington, Dakota County, MN

  19. A candidate gene study of canine joint diseases.

    PubMed

    Clements, Dylan N; Short, Andrea D; Barnes, Annette; Kennedy, Lorna J; Ferguson, John F; Butterworth, Steven J; Fitzpatrick, Noel; Pead, Matthew; Bennett, David; Innes, John F; Carter, Stuart D; Ollier, William E R

    2010-01-01

    Canine osteoarthritis (OA) commonly occurs in association with articular diseases, such as hip dysplasia (HD), elbow dysplasia (ED), or cranial cruciate ligament rupture (CCLR). We hypothesized that a common genomic risk for the development of canine joint disease and canine OA would be identified by evaluating the allele frequencies of candidate gene single nucleotide polymorphisms (SNPs) in dogs with OA associated with different articular diseases when compared with a general population of breed-matched dogs. DNA was extracted from blood samples obtained from Labrador Retrievers and Golden Retrievers surgically treated for ED, HD, and CCLR and confirmed to have radiographic evidence of OA. One hundred and thirteen SNPs in 20 candidate genes were genotyped. No significant associations were identified for SNPs or haplotypes in the candidate genes for the diseases evaluated. The candidate gene approach for the study of genetic association is unlikely to be successful for complex canine diseases such as OA without prior trait mapping evaluation.

  20. Death of a wild wolf from canine parvovirus enteritis

    USGS Publications Warehouse

    Mech, L.D.; Kurtz, H.J.; Goyal, S.

    1997-01-01

    A 9-mo-old female wolf (Canis lupus) in the Superior National Forest of Minnesota (USA) died from a canine parvovirus (CPV) infection. This is the first direct evidence that this infection effects free-ranging wild wolves.

  1. Management of Class II malocclusion with ectopic maxillary canines

    PubMed Central

    Mascarenhas, Rohan; Parveen, Shahista; Ansari, Tariq Aziz

    2015-01-01

    Correction of Class II relationship, deep bite and ectopically erupting canines is an orthodontic challenge for the clinician. A 13-year-old male patient presented with Class II malocclusion, ectopically erupting canines, and cross bite with maxillary left lateral incisor. He was treated with a combination of Headgear, Forsus™ fatigue resistant device [FFRD] with fixed mechanotherapy for the management of space deficiency and correction of Class II malocclusions. Headgear was used to distalize upper first molars and also to prevent further downward and forward growth of the maxilla. Then Forsus™ FFRD was used for the advancement of the mandible. The molar and canine relationship were corrected from a Class II to a Class I. The objectives were to establish good occlusion and enable eruption of unerupted canines. All these objectives were achieved and remained stable. PMID:26097371

  2. Bilateral agenesis of maxillary permanent canines: Review of the literature

    PubMed Central

    Borzabadi-Farahani, Ali

    2015-01-01

    Oligodontia, or agenesis of six or more teeth, excluding third molars, which involves canine agenesis is rare, and restorative management can be challenging. Bilateral agenesis of a permanent canine in the general population often indicates a several missing adult teeth. The most common sign of it is the primary canine retention beyond its exfoliation age. The multistage restorative management includes the early diagnosis, excluding associated medical problems as well as assessment of patient's malocclusion and facial skeletal pattern, life span of deciduous teeth, possibility of premolar substitution, minimum required number of prosthetic units, patient's preferences, and the cost of treatment. A 10-year-old boy with bilateral agenesis of maxillary permanent canines is described. Some thoughts on the multidisciplinary restorative management of this case are discussed. PMID:25657989

  3. Longitudinal study of viruses associated with canine infectious respiratory disease.

    PubMed

    Erles, Kerstin; Dubovi, Edward J; Brooks, Harriet W; Brownlie, Joe

    2004-10-01

    In this investigation a population of dogs at a rehoming center was monitored over a period of 2 years. Despite regular vaccination of incoming dogs against distemper, canine adenovirus type 2 (CAV-2), and canine parainfluenza virus (CPIV), respiratory disease was endemic. Tissue samples from the respiratory tract as well as paired serum samples were collected for analysis. The development of PCR assays for the detection of CPIV, canine adenovirus types 1 and 2, and canine herpesvirus (CHV) is described. Surprisingly, canine adenovirus was not detected in samples from this population, whereas 19.4% of tracheal and 10.4% of lung samples were positive for CPIV and 12.8% of tracheal and 9.6% of lung samples were positive for CHV. As reported previously, a novel canine respiratory coronavirus (CRCoV) was detected in this population (K. Erles, C. Toomey, H. W. Brooks, and J. Brownlie, Virology 310:216-223, 2003). Infections with CRCoV occurred mostly during the first week of a dog's stay at the kennel, whereas CPIV and CHV were detected at later time points. Furthermore, the evaluation of an enzyme-linked immunosorbent assay for detection of antibodies to CPIV and an immunofluorescence assay for detection of antibodies to CHV is described. This study shows that CPIV is present at kennels despite vaccination. In addition, other agents such as CHV and CRCoV may play a role in the pathogenesis of canine respiratory disease, whereas CAV-2 and canine distemper virus were not present in this population, indicating that their prevalence in the United Kingdom is low due to widespread vaccination of dogs.

  4. Effects of the zygoma anchorage system on canine retraction.

    PubMed

    Cetinsahin, Alev; Dinçer, Müfide; Arman-Ozçirpici, Ayça; Uçkan, Sina

    2010-10-01

    The aim of this study was to compare the effects of the Gjessing (PG) retraction spring used with and without the zygoma anchorage system (ZAS) on canine retraction. Thirty patients, with an Angle Class I or Class II malocclusion, whose upper first premolars were scheduled for extraction, were divided into two equal groups. Group 1 comprised maximum anchorage cases (nine females and six males with a mean age of 16 years 8 months) in which the ZAS was used to improve posterior anchorage and the PG retraction springs for canine retraction. Moderate anchorage cases (10 females and 5 males with a mean age of 15 years 5 month) were included in group 2 and canine retraction was achieved using only PG retraction springs. Study models and lateral cephalometric radiographs obtained at the initial and final stages of canine retraction were used for comparison of the groups to determine the effects of zygoma anchorage on canine retraction. All measurements were evaluated statistically using a Student's t-test, 2 × 2 repeated measures analysis of variance, Bonferroni-adjusted t-test, and Mann-Whitney U and Wilcoxon tests according to the normality of the distribution of the variables. Mesial crown movement of the molars was 0.63 mm (P < 0.05) in group 1 and 1.50 mm (P < 0.001) in group 2. There was a statistically significant difference (P < 0.05) between the groups. No significant difference was observed between the groups for the rate of canine retraction or sagittal and vertical movement of the canines. The ZAS is a reliable and successful anchorage reinforcement method for canine retraction in extraction cases.

  5. Alternative lengthening of telomeres does exist in various canine sarcomas.

    PubMed

    Kreilmeier, Theresa; Sampl, Sandra; Deloria, Abigail J; Walter, Ingrid; Reifinger, Martin; Hauck, Marlene; Borst, Luke B; Holzmann, Klaus; Kleiter, Miriam

    2017-03-01

    Alternative lengthening of telomeres (ALT) is a telomere maintenance mechanism (TMM) found in some human tumors such as sarcomas. Canine tumors are not characterized for ALT and the study aim was to identify if the ALT phenotype exists in canine sarcomas. Sixty-four canine sarcoma samples (20 snap-frozen, 44 FFPE) as well as six canine sarcoma cell lines were screened for ALT by C-circle assay. ALT was further evaluated by measuring telomere length via qPCR and telomere restriction-fragments including pulsed-field electrophoresis. ALT-associated proteins were validated by immunohistochemistry. Further, telomerase activity (TA) and gene expression were analyzed by TRAP and qPCR. DNA from 20 human neuroblastomas and 8 sarcoma cell lines served as comparative controls. ALT was detected in 9.4% (6/64) canine sarcomas including aggressive subtypes as hemangiosarcoma, osteosarcoma, and histiocytic sarcoma. C-circle levels were comparable with human ALT-positive controls. All ALT tumors demonstrated loss of ATRX expression and 5/6 showed strong p53 expression. TA was detected in 93% (14/15) snap-frozen samples including a sarcoma with ALT activity. This tumor showed long heterogeneous telomeres, and a high level of colocalization of DAXX with telomeres. One sarcoma was ALT and TA negative. All canine and human sarcoma cell lines were ALT negative. In this study, we demonstrated that canine sarcomas use ALT. As in humans, ALT was identified in aggressive sarcomas subtypes and coexisted with TA in one tumor. Overall, canine sarcomas seem to share many similarities with their human counterparts and appear an attractive model for comparative telomere research. © 2016 Wiley Periodicals, Inc.

  6. Longitudinal Study of Viruses Associated with Canine Infectious Respiratory Disease

    PubMed Central

    Erles, Kerstin; Dubovi, Edward J.; Brooks, Harriet W.; Brownlie, Joe

    2004-01-01

    In this investigation a population of dogs at a rehoming center was monitored over a period of 2 years. Despite regular vaccination of incoming dogs against distemper, canine adenovirus type 2 (CAV-2), and canine parainfluenza virus (CPIV), respiratory disease was endemic. Tissue samples from the respiratory tract as well as paired serum samples were collected for analysis. The development of PCR assays for the detection of CPIV, canine adenovirus types 1 and 2, and canine herpesvirus (CHV) is described. Surprisingly, canine adenovirus was not detected in samples from this population, whereas 19.4% of tracheal and 10.4% of lung samples were positive for CPIV and 12.8% of tracheal and 9.6% of lung samples were positive for CHV. As reported previously, a novel canine respiratory coronavirus (CRCoV) was detected in this population (K. Erles, C. Toomey, H. W. Brooks, and J. Brownlie, Virology 310:216-223, 2003). Infections with CRCoV occurred mostly during the first week of a dog's stay at the kennel, whereas CPIV and CHV were detected at later time points. Furthermore, the evaluation of an enzyme-linked immunosorbent assay for detection of antibodies to CPIV and an immunofluorescence assay for detection of antibodies to CHV is described. This study shows that CPIV is present at kennels despite vaccination. In addition, other agents such as CHV and CRCoV may play a role in the pathogenesis of canine respiratory disease, whereas CAV-2 and canine distemper virus were not present in this population, indicating that their prevalence in the United Kingdom is low due to widespread vaccination of dogs. PMID:15472304

  7. Three-year serologic immunity against canine parvovirus type 2 and canine adenovirus type 2 in dogs vaccinated with a canine combination vaccine.

    PubMed

    Larson, L J; Schultz, R D

    2007-01-01

    A group of client-owned dogs and a group of dogs at a commercial kennel were evaluated for duration of antibody responses against canine parvovirus type 2 (CPV-2) and canine adenovirus type 1 (CAV-1) after receiving a combination vaccine containing recombinant canarypox-vectored canine distemper virus (CDV) and modified-live CPV-2, CAV-2, and canine parainfluenza virus, with (C6) or without (C4) two serovars of Leptospira (Recombitek C4 or C6, Merial). Duration of antibody, which correlates with protective immunity, was found to be at least 36 months in both groups. Recombitek combination vaccines can confidently be given every 3 years with assurance of protection in immunocompetent dogs against CPV-2 and CAV-1 as well as CDV. This allows this combination vaccine, like other, similar modified- live virus combination products containing CDV, CAV-2, and CPV-2, to be administered in accordance with the recommendations of the American Animal Hospital Association Canine Vaccine Task Force.

  8. Acute Exercise-Induced Mitochondrial Stress Triggers an Inflammatory Response in the Myocardium via NLRP3 Inflammasome Activation with Mitophagy.

    PubMed

    Li, Haiying; Miao, Weiguo; Ma, Jingfen; Xv, Zhen; Bo, Hai; Li, Jianyu; Zhang, Yong; Ji, Li Li

    2016-01-01

    Increasing evidence has indicated that acute strenuous exercise can induce a range of adverse reactions including oxidative stress and tissue inflammation. However, little is currently known regarding the mechanisms that underlie the regulation of the inflammatory response in the myocardium during acute heavy exercise. This study evaluated the mitochondrial function, NLRP3 inflammasome activation, and mitochondrial autophagy-related proteins to investigate the regulation and mechanism of mitochondrial stress regarding the inflammatory response of the rat myocardium during acute heavy exercise. The results indicated that the mitochondrial function of the myocardium was adaptively regulated to meet the challenge of stress during acute exercise. The exercise-induced mitochondrial stress also enhanced ROS generation and triggered an inflammatory reaction via the NLRP3 inflammasome activation. Moreover, the mitochondrial autophagy-related proteins including Beclin1, LC3, and Bnip3 were all significantly upregulated during acute exercise, which suggests that mitophagy was stimulated in response to the oxidative stress and inflammatory response in the myocardium. Taken together, our data suggest that, during acute exercise, mitochondrial stress triggers the rat myocardial inflammatory response via NLRP3 inflammasome activation and activates mitophagy to minimize myocardial injury.

  9. A HPLC-fluorescence detection method for determination of phosphatidic acid phosphohydrolase activity: application in human myocardium.

    PubMed

    Burgdorf, Christof; Prey, Antje; Richardt, Gert; Kurz, Thomas

    2008-03-15

    Phosphatidic acid phosphohydrolase (PAP) catalyzes the dephosphorylation of phosphatidic acid (PA) to diacylglycerol, the second messenger responsible for activation of protein kinase C. Despite the crucial role of PAP lipid signaling, there are no data on PAP signaling function in the human heart. Here we present a nonradioactive assay for the investigation of PAP activity in human myocardium using a fluorescent derivative of PA, 2-(4,4-difluoro-5,7-dimethyl-4-bora-3a,4a-diaza-s-indacene-3-pentanoyl)-1-hexadecanoyl-sn-glycero-3-phosphate (BODIPY-PA), as substrate in an in vitro PAP-catalyzed reaction. Unreacted BODIPY-PA was resolved from the PAP products by a binary gradient HPLC system and BODIPY-diacylglycerol was detected by fluorimetry. The reaction proceeded at a linear rate for up to 60 min and increased linearly with increasing amounts of cardiac protein in a range of 0.25 to 8.0 microg. This assay proved to be sensitive for accurate quantitation of total PAP activity, PAP-1 activity, and PAP-2 activity in human atrial tissue and right ventricular endomyocardial biopsies. Total PAP activity was approximately fourfold higher in ventricular myocardium than in atrial tissue. There was negligible PAP-1 activity in atrial myocardium compared with ventricular myocardium, indicating regional differences in activities and distribution pattern of PAP-1 and PAP-2 in the human heart.

  10. [Levels of total hemolytic complement, C3, C4 and antibodies against the myocardium in rheumatic fever].

    PubMed

    Martinez, R D

    1978-01-01

    The levels of the hemolytic complement (UH 50%), C3, C4 and the antibodies against myocardium and against the antigenic fractions of myocardium precipitated with ammonium sulphate were studied in 8 patients with active rehumatic fever (ARF), 28 with inactive rheumatic fever (IRF) and 26 people without cardiopaties (NI). The UH 50% was low in 2 out of 36 patients with rheumatic fever (RF). C3 was normal and C4 low in 12.5% of the ARF patients. C3 had subnormal values in 25% and C4 in 33% of IRF patients, this last value had a stadistic significant decrease with respect to the values of C4 in normal people. The 36 patients with RF had antibodies against the myocardium and also against the heart antigenic fractions precipitated with 10% ammonium sulphate. 11.5% of the normal group had anti-myocardial antibodies and none had antibodies against the fractions. The levels of anti-streptolysin-O and C-reactive protein were higher in the ARF group than in the patients with IRF or the normal people. The participation of the hemolytic complement, the anti-myocardium antibodies, the anti-streptococcus antibodies and the cytophilic activity in the etiopathogeny of rheumatic fever is discussed.

  11. Liver X receptor activation protects against inflammation and enhances autophagy in myocardium of neonatal mouse challenged by lipopolysaccharides.

    PubMed

    Liu, Peng; He, Siyi; Gao, Junwei; Li, Jingwei; Fan, Xiaotang; Xiao, Ying-Bin

    2014-01-01

    Liver X receptors (LXRs) has been emerged as negative regulators of cardiomyocytic inflammation. The cellular process of autophagy is believed to play a protective role in myocardium during the inflammatory status. In this study, we investigated the role of LXRs agonist TO901317 (TO) on lipopolysaccharides (LPS)-induced myocardial inflammation and autophagy. The results showed that TO pretreatment significantly reduced the LPS-induced infiltration of inflammatory cells, elevation of NF-κB protein, TNF-α, and IL-6 mRNA levels in the myocardium. Moreover, LPS stimulated autophagy in neonatal mice heart, and this effect was further enhanced by TO pretreatment as evidenced by increased LC3-II/GAPDH ratio increment. Furthermore, TUNEL assay revealed LPS stimulation also increased the number of apoptotic cells in the myocardium, and the increment was inhibited by TO pretreatment. Our findings suggested that attenuation of inflammation and apoptosis, and enhancement of autophagy by TO may contribute to the protection of myocardium under inflammatory condition.

  12. Ultrasonographic evaluation of canine supraspinatus calcifying tendinosis.

    PubMed

    Mistieri, Maria Ligia A; Wigger, Antje; Canola, Julio C; Filho, João G P; Kramer, Martin

    2012-01-01

    Supraspinatus calcifying tendinosis is an uncommon finding in dogs. Although its radiographic appearance has been described previously, radiographs alone do not provide detailed information about the tendon parenchyma. Tendon ultrasonography has been widely applied for the diagnosis of human tendinosis, but it remains underused in dogs. This article reviews the ultrasonographic technique and variable appearance of canine supraspinatus calcifying tendinosis observed in 33 tendons. The ultrasonographic findings are described. The most common ultrasonographic finding was a hyperechoic area accompanied by distal acoustic shadowing. No relationship with bicipital tenosynovitis was found. A color Doppler examination was possible in only five of the tendons, revealing no blood flow in those tendons. There was evidence that the presence of a hypoechoic area surrounding the calcification was related to clinical signs of pain, suggesting an active inflammatory process. Ultrasonography was an excellent technique to evaluate lesions of the supraspinatus tendon and it revealed details not apparent on radiographs.

  13. Canine renal failure syndrome in three dogs.

    PubMed

    Jeong, Won Il; Do, Sun Hee; Jeong, Da Hee; Chung, Jae Yong; Yang, Hai Jie; Yuan, Dong Wei; Hong, Il Hwa; Park, Jin Kyu; Goo, Moon Jung; Jeong, Kyu Shik

    2006-09-01

    Three dead dogs were brought to the College of Veterinary Medicine, Kyungpook National University for study. Clinically, all the dogs showed emaciation, anorexia, depression, hemorrhagic vomiting and diarrhea for 7-10 days before death. All the clinical signs were first noted for about one month after feeding the dogs with commercial diets. At necropsy, all 3 dogs had severe renal damage with the same green-yellowish colored nephroliths in the renal pelvis. They also showed systemic hemorrhage and calcification of several organs, which might have been induced by uremia. Microscopically, necrosis, calcification and calculi were detected in the renal tubules, and especially in the proximal convoluted tubules and collecting ducts of the kidney. These findings were supportive of a mycotoxic effect, and especially on their kidneys. However, the precise cause of the toxic effect in these cases of canine renal failure could not be determined.

  14. Canine Distemper in Endangered Ethiopian Wolves

    PubMed Central

    Gordon, Christopher H.; Hussein, Alo; Laurenson, M. Karen; Malcolm, James R.; Marino, Jorgelina; Regassa, Fekede; Stewart, Anne-Marie E.; Fooks, Anthony R.; Sillero-Zubiri, Claudio

    2015-01-01

    The Ethiopian wolf (Canis simensis) is the world’s rarest canid; ≈500 wolves remain. The largest population is found within the Bale Mountains National Park (BMNP) in southeastern Ethiopia, where conservation efforts have demonstrated the negative effect of rabies virus on wolf populations. We describe previously unreported infections with canine distemper virus (CDV) among these wolves during 2005–2006 and 2010. Death rates ranged from 43% to 68% in affected subpopulations and were higher for subadult than adult wolves (83%–87% vs. 34%–39%). The 2010 CDV outbreak started 20 months after a rabies outbreak, before the population had fully recovered, and led to the eradication of several focal packs in BMNP’s Web Valley. The combined effect of rabies and CDV increases the chance of pack extinction, exacerbating the typically slow recovery of wolf populations, and represents a key extinction threat to populations of this highly endangered carnivore. PMID:25898177

  15. Canine distemper in endangered Ethiopian wolves.

    PubMed

    Gordon, Christopher H; Banyard, Ashley C; Hussein, Alo; Laurenson, M Karen; Malcolm, James R; Marino, Jorgelina; Regassa, Fekede; Stewart, Anne-Marie E; Fooks, Anthony R; Sillero-Zubiri, Claudio

    2015-05-01

    The Ethiopian wolf (Canis simensis) is the world's rarest canid; ≈500 wolves remain. The largest population is found within the Bale Mountains National Park (BMNP) in southeastern Ethiopia, where conservation efforts have demonstrated the negative effect of rabies virus on wolf populations. We describe previously unreported infections with canine distemper virus (CDV) among these wolves during 2005-2006 and 2010. Death rates ranged from 43% to 68% in affected subpopulations and were higher for subadult than adult wolves (83%-87% vs. 34%-39%). The 2010 CDV outbreak started 20 months after a rabies outbreak, before the population had fully recovered, and led to the eradication of several focal packs in BMNP's Web Valley. The combined effect of rabies and CDV increases the chance of pack extinction, exacerbating the typically slow recovery of wolf populations, and represents a key extinction threat to populations of this highly endangered carnivore.

  16. Muscle disorders and rehabilitation in canine athletes.

    PubMed

    Steiss, Janet E

    2002-01-01

    Muscle disorders associated with physical exertion in human athletes include delayed-onset muscle soreness, muscle strain, muscle tears, rhabdomyolysis, and acute and chronic compartment syndromes. Given that the structure of muscle is similar among different species, it is reasonable to expect that dogs experience the same phenomena. This article focuses on several of the muscle disorders of bird dogs, namely, coccygeal muscle injury and infraspinatus muscle contracture, and on those of dogs involved in tracking-obedience-protection training, namely, fibrotic myopathy, with an additional discussion of muscle strain. For injury prevention, one important area that can be adapted to canine athletes is the incorporation of warm-up and cool-down into the training program.

  17. Immunohistochemical characteristics of normal canine eyes.

    PubMed

    Labelle, P; Reilly, C M; Naydan, D K; Labelle, A L

    2012-09-01

    Immunohistochemistry is widely utilized in diagnostic laboratories to study neoplastic and nonneoplastic diseases. Knowledge of the immunohistochemical characteristics of normal tissue is essential for interpretation of immunoreactivity in pathologic conditions. In this study, immunohistochemistry was performed with a broad panel of diagnostically relevant antibodies on 4 normal canine globes--namely, vimentin, pan-cytokeratin (AE1/AE3), cytokeratin 7, cytokeratin 8/18, cytokeratin 20, α-smooth muscle actin, muscle specific actin, desmin, Melan-A, microphthalmia transcription factor, S-100, glial fibrillary acidic protein, triple neurofilaments, neuron-specific enolase, chromogranin A, synaptophysin, laminin and CD31. Results include cytokeratin immunoreactivity limited to the conjunctival epithelium, corneal epithelium, and retinal pigment epithelium; distinct patterns of immunopositivity of muscle markers; and widespread immunoreactivity for vimentin and most neural/neuroendocrine markers. These findings in normal eyes provide the basis for interpretation of ocular immunohistochemistry in dogs. Published immunophenotypes of primary ocular neoplasms are also reviewed.

  18. Canine vector-borne diseases in Brazil

    PubMed Central

    Dantas-Torres, Filipe

    2008-01-01

    Canine vector-borne diseases (CVBDs) are highly prevalent in Brazil and represent a challenge to veterinarians and public health workers, since some diseases are of great zoonotic potential. Dogs are affected by many protozoa (e.g., Babesia vogeli, Leishmania infantum, and Trypanosoma cruzi), bacteria (e.g., Anaplasma platys and Ehrlichia canis), and helminths (e.g., Dirofilaria immitis and Dipylidium caninum) that are transmitted by a diverse range of arthropod vectors, including ticks, fleas, lice, triatomines, mosquitoes, tabanids, and phlebotomine sand flies. This article focuses on several aspects (etiology, transmission, distribution, prevalence, risk factors, diagnosis, control, prevention, and public health significance) of CVBDs in Brazil and discusses research gaps to be addressed in future studies. PMID:18691408

  19. Calcareous degeneration of the canine cornea.

    PubMed

    Sansom, Jane; Blunden, Tony

    2010-07-01

    The purpose of this paper is to describe a specific presentation of canine corneal calcification. Fourteen cases are described. In seven cases the corneal lesions were bilaterally symmetrical. In five cases the corneal lesion was unilateral. Two dogs were uniocular, the contralateral eye had been enucleated between 1 and 3 months previously by the referring veterinary surgeon following corneal ulceration and perforation. Of a total of 21 eyes with corneal calcification, 16 eyes had associated ulceration. The ulceration presented as follows: two eyes had descemetocoeles, four eyes had corneal perforations, eight eyes had stromal ulceration, and two eyes had superficial punctate ulceration. The cause of the corneal mineralization remains undetermined but underlying systemic disease, particularly hyperadrenocorticism (Cushing's Syndrome), is suspected as a possible contributing factor in some of these cases. Histopathology was carried out on three cases following a keratectomy and placement of a conjunctival pedicle flap into the ulcerated lesion.

  20. Why segment the maxilla between laterals and canines?

    PubMed Central

    Esteves, Lucas Senhorinho; dos Santos, Jean Nunes; Sullivan, Steven M.; Martins, Luana Maria Rosário; Ávila, Carolina

    2016-01-01

    Introduction: Maxillary surgery on a bone segment enables movement in the sagittal and vertical planes. When performed on multiple segments, it further provides movement in the transverse plane. Typical sites for interdental osteotomies are between laterals and canines, premolars and canines, or between incisors. Additionally, osteotomies can be bilateral, unilateral or asymmetric. The ability to control intercanine width, buccolingual angulation of incisors, and correct Bolton discrepancy are some of the advantages of maxillary segmentation between laterals and canines. Objective: This article describes important features to be considered in making a clinical decision to segment the maxilla between laterals and canines when treating a dentoskeletal deformity. It further discusses the history of this surgical approach, the indications for its clinical use, the technique used to implement it, as well as its advantages, disadvantages, complications and stability. It is therefore hoped that this paper will contribute to disseminate information on this topic, which will inform the decision-making process of those professionals who wish to make use of this procedure in their clinical practice. Conclusions: Segmental maxillary osteotomy between laterals and canines is a versatile technique with several indications. Furthermore, it offers a host of advantages compared with single-piece osteotomy, or between canines and premolars. PMID:27007769