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Jens Haggstrom - One of the best experts on this subject based on the ideXlab platform.
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longitudinal analysis of quality of life clinical radiographic echocardiographic and laboratory variables in dogs with preclinical myxomatous mitral valve disease receiving pimobendan or placebo the epic study
Journal of Veterinary Internal Medicine, 2018Co-Authors: A Boswood, Bruce W Keene, Sonya G Gordon, Jens Haggstrom, Gerhard Wess, Rebecca L Stepien, Mark A Oyama, John D Bonagura, Kristin A Macdonald, M PattesonAbstract:Background Changes in clinical variables associated with the administration of pimobendan to dogs with preclinical myxomatous mitral valve disease (MMVD) and cardiomegaly have not been described. Objectives To investigate the effect of pimobendan on clinical variables and the relationship between a change in Heart Size and the time to congestive Heart failure (CHF) or cardiac-related death (CRD) in dogs with MMVD and cardiomegaly. To determine whether pimobendan-treated dogs differ from dogs receiving placebo at onset of CHF. Animals Three hundred and fifty-four dogs with MMVD and cardiomegaly. Materials and methods Prospective, blinded study with dogs randomized (ratio 1:1) to pimobendan (0.4-0.6 mg/kg/d) or placebo. Clinical, laboratory, and Heart-Size variables in both groups were measured and compared at different time points (day 35 and onset of CHF) and over the study duration. Relationships between short-term changes in echocardiographic variables and time to CHF or CRD were explored. Results At day 35, Heart Size had reduced in the pimobendan group: median change in (Δ) LVIDDN -0.06 (IQR: -0.15 to +0.02), P Conclusions and clinical importance Pimobendan treatment reduces Heart Size. Reduced Heart Size is associated with improved outcome. At the onset of CHF, dogs treated with pimobendan were indistinguishable from those receiving placebo.
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longitudinal analysis of quality of life clinical radiographic echocardiographic and laboratory variables in dogs with myxomatous mitral valve disease receiving pimobendan or benazepril the quest study
Journal of Veterinary Internal Medicine, 2013Co-Authors: Jens Haggstrom, Michael R Ogrady, Olaf Jons, A Boswood, Sarah Smith, Simon Swift, M Borgarelli, B Gavaghan, Jangerd Kresken, M PattesonAbstract:BACKGROUND: Myxomatous mitral valve disease (MMVD) is an important cause of morbidity and mortality in dogs. OBJECTIVES: To compare, throughout the period of follow-up of dogs that had not yet reached the primary endpoint, the longitudinal effects of pimobendan versus benazepril hydrochloride treatment on quality-of-life (QoL) variables, concomitant congestive Heart failure (CHF) treatment, and other outcome variables in dogs suffering from CHF secondary to MMVD. ANIMALS: A total of 260 dogs in CHF because of MMVD. METHODS: A prospective single-blinded study with dogs randomized to receive pimobendan (0.4-0.6 mg/kg/day) or benazepril hydrochloride (0.25-1.0 mg/kg/day). Differences in outcome variables and time to intensification of CHF treatment were compared. RESULTS: A total of 124 dogs were randomized to pimobendan and 128 to benazepril. No difference was found between groups in QoL variables during the trial. Time from inclusion to 1st intensification of CHF treatment was longer in the pimobendan group (pimobendan 98 days, IQR 30-276 days versus benazepril 59 days, IQR 11-121 days; P = .0005). Postinclusion, dogs in the pimobendan group had smaller Heart Size based on VHS score (P = .013) and left ventricular diastolic (P = .035) and systolic (P = .0044) dimensions, higher body temperature (P = .030), serum sodium (P = .0027), and total protein (P = .0003) concentrations, and packed cell volume (P = .030). Incidence of arrhythmias was similar in treatment groups. CONCLUSIONS AND CLINICAL IMPORTANCE: Pimobendan versus benazepril resulted in similar QoL during the study, but conferred increased time before intensification of CHF treatment. Pimobendan treatment resulted in smaller Heart Size, higher body temperature, and less retention of free water.
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short term hemodynamic and neuroendocrine effects of pimobendan and benazapril in dogs with myxomatous mitral valve disease and congestive Heart failure
Journal of Veterinary Internal Medicine, 2013Co-Authors: Jens Haggstrom, Olaf Jons, P Lord, Katja Hoglund, I Ljungvall, C Kvart, Kerstin HanssonAbstract:Background Pimobendan and benazepril are frequently used with diuretics to treat dogs in congestive Heart failure (CHF) caused by myxomatous mitral valve disease (MMVD). Aim To compare the short-term effects of pimobendan versus benazepril on pump function, Heart Size, and neuroendocrine profile in dogs with CHF caused by MMVD. Animals Sixteen client-owned dogs. Material and methods Seven-day prospective single-blinded study of dogs stabilized on furosemide monotherapy, randomized to pimobendan (0.4–0.6 mg/kg/day) or benazepril (0.25–1.0 mg/kg/day). Dogs had first-pass radionuclide angiocardiography, and Heart Size was measured by radiography and echocardiography. Circulating neuroendocrine hormones were measured. Results Baseline variables did not differ between treatment groups. Greater decreases in the pimobendan than in the benazepril group were found for Heart rate (P = .001), Heart rate-normalized pulmonary transit time (P = .02), left atrial Size (P = .03), and systolic and diastolic left ventricular diameters (P < .001 and P = .03, respectively) and volumes (P < .001 and P = .02, respectively), whereas ejection fraction increased more (P = .02) in the pimobendan group. Of the neuroendocrine hormones, only N-terminal proatrial natriuretic peptide (NT-ProANP) differed (P = .04) between groups. Within groups, plasma aldosterone increased (P = .01), and NT-proANP (P = .01) and NT-proB-type (P = .02) natriuretic peptide decreased in the pimobendan group, and NT-proANP (P = .02) and plasma vasopressin (P = .01) decreased in the benazepril group. Conclusions and Clinical Importance Pimobendan improves short-term cardiac function more than benazepril in dogs with CHF caused by MMVD. Pimobendan treatment enables the Heart to work at smaller end-systolic and diastolic dimensions while maintaining adequate forward stroke volume. Some of the treatment responses found in neuroendocrine profile might have therapeutic relevance.
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rate of change of Heart Size before congestive Heart failure in dogs with mitral regurgitation
Journal of Small Animal Practice, 2010Co-Authors: Peter Lord, Kerstin Hansson, C Kvart, Jens HaggstromAbstract:Objectives: The objective of the study was to examine the changes in vertebral Heart scale, and left atrial and ventricular dimensions before and at onset of congestive Heart failure in cavalier King Charles spaniels with mitral regurgitation. Methods: Records and radiographs from 24 cavalier King Charles spaniels with mitral regurgitation were used. Vertebral Heart scale (24 dogs), and left atrial dimension and left ventricular end diastolic and end systolic diameters (18 dogs) and their rate of increase were measured at intervals over years to the onset of congestive Heart failure. They were plotted against time to onset of congestive Heart failure. Results: Dimensions and rates of change of all parameters were highest at onset of congestive Heart failure, the difference between observed and chance outcome being highly significant using a two-tailed chi-square test (P<0·001). Clinical significance: The left Heart chambers increase in Size rapidly only in the last year before the onset of congestive Heart failure. Increasing left ventricular end systolic dimension is suggestive of myocardial failure before the onset of congestive Heart failure. Rate of increase of Heart dimensions may be a useful indicator of impending congestive Heart failure.
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interobserver variability of vertebral Heart Size measurements in dogs with normal and enlarged Hearts
Veterinary Radiology & Ultrasound, 2005Co-Authors: Kerstin Hansson, Jens Haggstrom, C Kvart, Peter LordAbstract:The vertebral Heart Size (VHS) method by Buchanan is based on anatomic landmarks. A potential source of variation among observers is differences in the selection of measurement points. The objective was to test variability between observers with different levels of training in thoracic radiology and small animal clinical practice. Fifty sets of thoracic radiographs of cavalier King Charles spaniels, were divided into five groups; (Normal) normal cardiopulmonary structures, (I) slight cardiomegaly, (II) moderate cardiomegaly, (II +) moderate cardiomegaly with congestive Heart failure, and (III +) severe cardiomegaly with congestive Heart failure. Cardiomegaly was confirmed by echocardiography to be caused by mitral regurgitation because of myxomatous mitral valve disease. Sixteen observers representing four levels of experience (four observers/level) evaluated the radiographs; (1) European Diplomates in Veterinary Diagnostic Imaging, (2) Experienced small animal clinicians, (3) Trainees in small animal clinical practice (4) Veterinary students. Almost identical mean VHS values were found among the four experience levels for each of the five groups of radiographs with a low coefficient of variation, range 1.5-3.2%. Mean difference among the 16 observers was 1.05 +/- 0.32 vertebrae (v). Mean difference among individuals in each observer group was approximately 0.5 v for all but the groups of trainees were the difference was 0.6-0.9 v. The conclusion is that VHS method for Heart Size is independent of observer experience but dependent of individual observers selection of reference points and transformation of long and short axis dimensions into VHS units.
M Patteson - One of the best experts on this subject based on the ideXlab platform.
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longitudinal analysis of quality of life clinical radiographic echocardiographic and laboratory variables in dogs with preclinical myxomatous mitral valve disease receiving pimobendan or placebo the epic study
Journal of Veterinary Internal Medicine, 2018Co-Authors: A Boswood, Bruce W Keene, Sonya G Gordon, Jens Haggstrom, Gerhard Wess, Rebecca L Stepien, Mark A Oyama, John D Bonagura, Kristin A Macdonald, M PattesonAbstract:Background Changes in clinical variables associated with the administration of pimobendan to dogs with preclinical myxomatous mitral valve disease (MMVD) and cardiomegaly have not been described. Objectives To investigate the effect of pimobendan on clinical variables and the relationship between a change in Heart Size and the time to congestive Heart failure (CHF) or cardiac-related death (CRD) in dogs with MMVD and cardiomegaly. To determine whether pimobendan-treated dogs differ from dogs receiving placebo at onset of CHF. Animals Three hundred and fifty-four dogs with MMVD and cardiomegaly. Materials and methods Prospective, blinded study with dogs randomized (ratio 1:1) to pimobendan (0.4-0.6 mg/kg/d) or placebo. Clinical, laboratory, and Heart-Size variables in both groups were measured and compared at different time points (day 35 and onset of CHF) and over the study duration. Relationships between short-term changes in echocardiographic variables and time to CHF or CRD were explored. Results At day 35, Heart Size had reduced in the pimobendan group: median change in (Δ) LVIDDN -0.06 (IQR: -0.15 to +0.02), P Conclusions and clinical importance Pimobendan treatment reduces Heart Size. Reduced Heart Size is associated with improved outcome. At the onset of CHF, dogs treated with pimobendan were indistinguishable from those receiving placebo.
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longitudinal analysis of quality of life clinical radiographic echocardiographic and laboratory variables in dogs with myxomatous mitral valve disease receiving pimobendan or benazepril the quest study
Journal of Veterinary Internal Medicine, 2013Co-Authors: Jens Haggstrom, Michael R Ogrady, Olaf Jons, A Boswood, Sarah Smith, Simon Swift, M Borgarelli, B Gavaghan, Jangerd Kresken, M PattesonAbstract:BACKGROUND: Myxomatous mitral valve disease (MMVD) is an important cause of morbidity and mortality in dogs. OBJECTIVES: To compare, throughout the period of follow-up of dogs that had not yet reached the primary endpoint, the longitudinal effects of pimobendan versus benazepril hydrochloride treatment on quality-of-life (QoL) variables, concomitant congestive Heart failure (CHF) treatment, and other outcome variables in dogs suffering from CHF secondary to MMVD. ANIMALS: A total of 260 dogs in CHF because of MMVD. METHODS: A prospective single-blinded study with dogs randomized to receive pimobendan (0.4-0.6 mg/kg/day) or benazepril hydrochloride (0.25-1.0 mg/kg/day). Differences in outcome variables and time to intensification of CHF treatment were compared. RESULTS: A total of 124 dogs were randomized to pimobendan and 128 to benazepril. No difference was found between groups in QoL variables during the trial. Time from inclusion to 1st intensification of CHF treatment was longer in the pimobendan group (pimobendan 98 days, IQR 30-276 days versus benazepril 59 days, IQR 11-121 days; P = .0005). Postinclusion, dogs in the pimobendan group had smaller Heart Size based on VHS score (P = .013) and left ventricular diastolic (P = .035) and systolic (P = .0044) dimensions, higher body temperature (P = .030), serum sodium (P = .0027), and total protein (P = .0003) concentrations, and packed cell volume (P = .030). Incidence of arrhythmias was similar in treatment groups. CONCLUSIONS AND CLINICAL IMPORTANCE: Pimobendan versus benazepril resulted in similar QoL during the study, but conferred increased time before intensification of CHF treatment. Pimobendan treatment resulted in smaller Heart Size, higher body temperature, and less retention of free water.
Henning Gall - One of the best experts on this subject based on the ideXlab platform.
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right ventricular Size and function under riociguat in pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension the river study
Respiratory Research, 2018Co-Authors: Alberto M Marra, Michael Halank, Nicola Benjamin, Eduardo Bossone, Antonio Cittadini, Christina A Eichstaedt, Benjamin Egenlauf, Satenik Harutyunova, Christine Fischer, Henning GallAbstract:Riociguat is a soluble guanylate cyclase stimulator approved for pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTPEH). The objective of this study was to evaluate right Heart Size and function assessed by echocardiography during long term treatment with riociguat. Patients who started riociguat treatment (1.0–2.5 mg tid) within the trials phase II, PATENT, PATENTplus, EAS, CHEST and continued treatment for 3–12 months were included in this study. Echocardiography was analysed off-line at baseline, after 3, 6 and 12 months by investigators who were blinded to clinical data. Last and baseline observation carried forward method (LOCF, BOCF) were performed as sensitivity analysis. Seventy-one patients (45% PAH, 55% CTEPH; 53.5% female; 60 ± 13 years, mean pulmonary arterial pressure 46 ± 10 mmHg, mean PVR 700 ± 282dynes·sec·cm-5) were included. After 6 months, RA and RV area, RV thickness tricuspid regurgitation velocity showed a significant reduction. After 12 months, patients receiving riociguat therapy showed a significant reduction in right atrial (− 2.6 ± 4.4 cm2, 95% CI -3.84, − 1.33; p < 0.001, n = 49) and right ventricular (RV) area (− 3.5 ± 5.2 cm2, 95% CI -5.1, − 1.9; p < 0.001; n = 44), RV thickness (− 0.76 ± 2.2 mm, 95% CI -1.55, 0.03; n = 32), and a significant increase in TAPSE (2.95 ± 4.78 mm, 95% CI 1.52, 4.39; n = 45) and RV fractional area change (8.12 ± 8.87 mm, 95% CI 4.61, 11.62; n = 27). Both LOCF and BOCF showed similar results but lower effect Sizes. Patients under long-term treatment with riociguat show significantly reduced right Heart Size and improved RV function in PAH and CTEPH. Further controlled prospective studies are needed to confirm these results.
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change of right Heart Size and function by long term therapy with riociguat in patients with pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension
International Journal of Cardiology, 2015Co-Authors: Alberto M Marra, Michael Halank, Eduardo Bossone, Antonio Cittadini, Christina A Eichstaedt, Benjamin Egenlauf, Christine Fischer, Nicola Ehlken, Christian Nagel, Henning GallAbstract:Abstract Background Riociguat is a soluble guanylate cyclase stimulator approved for pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH). The objective of this study was to evaluate the change of right Heart Size and function assessed by echocardiography during long-term treatment with riociguat. Methods We assessed patients who started riociguat treatment (1.0–2.5mg tid) within the trials PATENT, PATENTplus, EAS and CHEST and continued for 3–12months. Echocardiography, 6-minute walking distance (6MWD) and further clinical parameters were analyzed at baseline, after 3, 6 and 12months. Right Heart catheterization was performed at baseline and after 3months. For missing data we performed the last and baseline observation carried forward (LOCF, BOCF) method as sensitivity analyses. Results Thirty-nine patients (21 PAH, 18 CTEPH, mean pulmonary arterial pressure 43±2mmHg, PVR 600±43dyn∗s∗cm −5 , 56.4% treatment-naive) were included. Mean right ventricular (RV) area significantly decreased after 3 (−2.1±3.9cm 2 , equals −7.4±15.3%, p=0.002), 6 (−4.2±3.2cm 2 , equals −16.1±11.5%, p 2 , equals −22.1±14.2%, p 2 , equals −16.8±19.2%, p Conclusion Long-term treatment with riociguat significantly reduced right Heart Size and improved RV function in PAH and CTEPH. Further prospective studies are needed to confirm these results.
Karl A Nibbelink - One of the best experts on this subject based on the ideXlab platform.
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characterization of Heart Size and blood pressure in the vitamin d receptor knockout mouse
The Journal of Steroid Biochemistry and Molecular Biology, 2007Co-Authors: Robert U Simpson, Steven H Hershey, Karl A NibbelinkAbstract:Abstract Our previous studies showed vitamin D deficiency results in increased cardiac contractility, hypertrophy and fibrosis and has profound effects on Heart proteomics, structure and function in rat. In this study we found that the Heart in vitamin D receptor knockout (VDR-KO) mice is hypertrophied. Six homozygous VDR knockout (−/−), six wild type (+/+) and six heterozygous (+/−) mice were fed a diet containing 2% Ca, 1.25% P and 20% lactose to maintain normal blood calcium and phosphate levels for 12 months. Tail-cuff blood pressure was performed on all mice. Blood pressure determinations showed no differences in systolic or mean blood pressure in WT (+/+), KO (−/−) or HETERO (+/−) mice at 3 and 6 months. However, decreased systolic BP in the KO mice relative to WT at 9 months of age was observed. ECG analysis showed no significant differences in the intact KO, HETERO or WT mice. The mice were killed at 12 months. Heart weight/body weight ratio was 41% ( P P directly on the Heart as a tranquilizer by blunting cardiomyocyte hypertrophy.
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characterization of Heart Size and blood pressure in the vitamin d receptor knockout mouse
The Journal of Steroid Biochemistry and Molecular Biology, 2007Co-Authors: Robert U Simpson, Steven H Hershey, Karl A NibbelinkAbstract:Our previous studies showed vitamin D deficiency results in increased cardiac contractility, hypertrophy and fibrosis and has profound effects on Heart proteomics, structure and function in rat. In this study we found that the Heart in vitamin D receptor knockout (VDR-KO) mice is hypertrophied. Six homozygous VDR knockout (-/-), six wild type (+/+) and six heterozygous (+/-) mice were fed a diet containing 2% Ca, 1.25% P and 20% lactose to maintain normal blood calcium and phosphate levels for 12 months. Tail-cuff blood pressure was performed on all mice. Blood pressure determinations showed no differences in systolic or mean blood pressure in WT (+/+), KO (-/-) or HETERO (+/-) mice at 3 and 6 months. However, decreased systolic BP in the KO mice relative to WT at 9 months of age was observed. ECG analysis showed no significant differences in the intact KO, HETERO or WT mice. The mice were killed at 12 months. Heart weight/body weight ratio was 41% (P<.003) greater in the KO mice versus WT and HETERO was 19% (P<.05) increased versus WT. Other VDR-KO tissues did not display hypertrophy. Cross sectional and longitudinal analysis of the Heart myofibrils showed highly significant cellular hypertrophy in VDR-KO mice. Trichrome staining of Heart tissue showed marked increase in fibrotic lesions in the KO mice. Analysis of plasma renin activity, angiotensin II (AII) and aldosterone levels showed elevated but not significantly different renin activity in KO versus WT and no significant differences in AII or aldosterone levels. Our data do not support the concept that the renin-angiotensin system or hypertension are the factors that elicit these changes. Data presented here reveal that ablation of the VDR signaling system results in profound changes in Heart structure. We propose that calcitriol acts directly on the Heart as a tranquilizer by blunting cardiomyocyte hypertrophy.
Seigo Izumo - One of the best experts on this subject based on the ideXlab platform.
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akt protein kinase b promotes organ growth in transgenic mice
Molecular and Cellular Biology, 2002Co-Authors: Tetsuo Shioi, Julie R Mcmullen, Peter M Kang, Pamela S Douglas, Lewis C Cantley, Toshiyuki Obata, Thomas F Franke, Seigo IzumoAbstract:One of the least-understood areas in biology is the determination of the Size of animals and their organs. In Drosophila, components of the insulin receptor phosphoinositide 3-kinase (PI3K) pathway determine body, organ, and cell Size. Several biochemical studies have suggested that Akt/protein kinase B is one of the important downstream targets of PI3K. To examine the role of Akt in the regulation of organ Size in mammals, we have generated and characterized transgenic mice expressing constitutively active Akt (caAkt) or kinase-deficient Akt (kdAkt) specifically in the Heart. The Heart weight of caAkt transgenic mice was increased 2.0-fold compared with that of nontransgenic mice. The increase in Heart Size was associated with a comparable increase in myocyte cell Size in caAkt mice. The kdAkt mutant protein attenuated the constitutively active PI3K-induced overgrowth of the Heart, and the caAkt mutant protein circumvented cardiac growth retardation induced by a kinase-deficient PI3K mutant protein. Rapamycin attenuated caAkt-induced overgrowth of the Heart, suggesting that the mammalian target of rapamycin (mTOR) or effectors of mTOR mediated caAkt-induced Heart growth. In conclusion, Akt is sufficient to induce a marked increase in Heart Size and is likely to be one of the effectors of the PI3K pathway in mediating Heart growth.
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the conserved phosphoinositide 3 kinase pathway determines Heart Size in mice
The EMBO Journal, 2000Co-Authors: Tetsuo Shioi, Peter M Kang, Pamela S Douglas, James Hampe, Claudine M Yballe, Joel Lawitts, Lewis C Cantley, Seigo IzumoAbstract:Phosphoinositide 3-kinase (PI3K) has been shown to regulate cell and organ Size in Drosophila, but the role of PI3K in vertebrates in vivo is not well understood. To examine the role of PI3K in intact mammalian tissue, we have created and characterized transgenic mice expressing constitutively active or dominant-negative mutants of PI3K in the Heart. Cardiac- specific expression of constitutively active PI3K resulted in mice with larger Hearts, while dominant-negative PI3K resulted in mice with smaller Hearts. The increase or decrease in Heart Size was associated with comparable increase or decrease in myocyte Size. Cardiomyopathic changes, such as myocyte necrosis, apoptosis, interstitial fibrosis or contractile dysfunction, were not observed in either of the transgenic mice. Thus, the PI3K pathway is necessary and sufficient to promote organ growth in mammals.
