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Emmanuel Boulay, Michael K Pugsley, Vincent Jacquemet, Alain Vinet, Michael V Accardi, Maxim Soloviev, Eric Troncy, Jennifer M Doyle, Jennifer Beck Pierson, Simon Authier
INTRODUCTION: QT has a long history of heart rate (HR) correction but limited investigations have been undertaken to assess the impact of cardiovascular parameters on left ventricular (LV) contractility in drug safety testing. Cardiac contractility is affected by preload (Cyon-Frank-Starling law), afterload (Anrep effect) and HR (Bowditch effect). We evaluated multi-parameter correction methods to help with dP/dtmax interpretation. METHODOLOGY: Modeling was undertaken using data from dogs in single or double 4×4 Latin square studies...
April 20, 2017: Journal of Pharmacological and Toxicological Methods
Michael K Pugsley, Brian Guth, Alan Y Chiang, Jennifer M Doyle, Michael Engwall, Jean-Michel Guillon, Peter K Hoffmann, John E Koerner, Scott W Mittelstadt, Jennifer Beck Pierson, Eric I Rossman, Dustan R Sarazan, Stanley T Parish
INTRODUCTION: The importance of drug-induced effects on the inotropic state of the heart is well known. Unlike hemodynamic and cardiac electrophysiological methods, which have been routinely used in drug safety testing for years, the non-clinical assessment of drug effects on myocardial contractility is used less frequently with no established translation to humans. The goal of these studies was to determine whether assessment of alternate measures of cardiac inotropy could detect drug-induced changes in the contractile state of the heart using drugs known to have clinically relevant positive and negative effects on myocardial contractility...
January 5, 2017: Journal of Pharmacological and Toxicological Methods
Maximilian Kreibich, Michael Berchtold-Herz, Friedhelm Beyersdorf, Georg Trummer
We report the case of a 76-year-old patient who developed chronic right heart failure 1 year after left ventricular assist device implantation due to ischemic cardiomyopathy. Initial recompensation was achieved through dobutamin, sildenafil, and levosimendan treatment. Yet, discharge was successful only after the off-label use of the oral calcium sensitizer pimobendan. Ten months after discharge, the patient presents with no clinical signs of right heart failure and significantly improved right heart function without any impairment in quality of life...
December 2016: Thoracic and Cardiovascular Surgeon Reports
R A Santilli, S Battaia, M Perego, M Tursi, E Grego, C Marzufero, P Gianella
A 6-year-old, male, mongrel dog was presented for acute onset of dyspnea and cough. At admission, the dog was cachectic and severely depressed. The electrocardiogram showed a sinus rhythm conducted with left bundle truncular branch block and interrupted by frequent multiform ventricular ectopic beats organized in allorhythmias. Thoracic radiographs revealed a marked cardiomegaly with perihilar edema, whereas transthoracic echocardiography revealed a dilated cardiomyopathy with segmental dyskinesis. Furosemide, enalapril, pimobendan, and mexiletine were prescribed, and a Holter was scheduled after resolution of congestive heart failure...
February 2017: Journal of Veterinary Cardiology: the Official Journal of the European Society of Veterinary Cardiology
Lara Cusack, Cara Field, Alexa McDermott, Brandon Pogue, Tonya Clauss, Gregory Bossart, Alvin Camus
A 19-year-old male African penguin ( Spheniscus demersus ) was presented with coelomic distention after a 6-week history of lethargy and decreased appetite. Results of radiographs showed loss of coelomic detail, and ultrasound and computed tomography results revealed coelomic fluid and dilated hepatic veins. Echocardiography revealed moderate right atrial enlargement. Findings were consistent with right-sided cardiac disease. Treatment with furosemide initially reduced ascites, but the clinical condition worsened weeks later and enalapril, pimobendan, and sildenafil were added to the medical therapy...
September 2016: Journal of Avian Medicine and Surgery
Jooyae Paik, Ji-Houn Kang, Dongwoo Chang, Mhan-Pyo Yang
A 5 yr old intact female cocker spaniel dog weighing 7.8 kg was referred with anorexia, vomiting, and depression. At referral, the dog was diagnosed initially with typical hypoadrenocorticism, and 2 d later, concurrent primary hypothyroidism was detected. Hormonal replacement therapies, including fludrocortisone, prednisolone, and levothyroxine, were initiated, but a few days later the dog became abruptly tachypneic, and thoracic radiographs indicated the development of pulmonary edema. Echocardiography showed that there were abnormalities indicating impaired left ventricular function, although the heart valves were normal...
November 2016: Journal of the American Animal Hospital Association
A Boswood, J Häggström, S G Gordon, G Wess, R L Stepien, M A Oyama, B W Keene, J Bonagura, K A MacDonald, M Patteson, S Smith, P R Fox, K Sanderson, R Woolley, V Szatmári, P Menaut, W M Church, M L O'Sullivan, J-P Jaudon, J-G Kresken, J Rush, K A Barrett, S L Rosenthal, A B Saunders, I Ljungvall, M Deinert, E Bomassi, A H Estrada, M J Fernandez Del Palacio, N S Moise, J A Abbott, Y Fujii, A Spier, M W Luethy, R A Santilli, M Uechi, A Tidholm, P Watson
BACKGROUND: Pimobendan is effective in treatment of dogs with congestive heart failure (CHF) secondary to myxomatous mitral valve disease (MMVD). Its effect on dogs before the onset of CHF is unknown. HYPOTHESIS/OBJECTIVES: Administration of pimobendan (0.4-0.6 mg/kg/d in divided doses) to dogs with increased heart size secondary to preclinical MMVD, not receiving other cardiovascular medications, will delay the onset of signs of CHF, cardiac-related death, or euthanasia...
November 2016: Journal of Veterinary Internal Medicine
Masashi Mizuno, Shigeki Yamano, Shuichi Chimura, Atsushi Hirakawa, Yoshimi Takusagawa, Tamotsu Sawada, Shigeki Maetani, Arane Takahashi, Takeshi Mizuno, Kayoko Harada, Asako Shinoda, Shuhei Uchida, Junichiro Takeuchi, Takahiro Mizukoshi, Masaaki Endo, Masami Uechi
The aim of this study was to evaluate the efficacy of pimobendan with conventional therapies on survival and reocurrence of pulmonary edema in dogs with congestive heart failure (CHF) caused by myxomatous mitral valve disease (MMVD). Records of 197 client-owned dogs from 14 veterinary hospitals were included in this study. Dogs were administered conventional treatments with or without pimobendan. Sixty-four dogs received a standard dose of pimobendan (0.20-0.48 mg/kg every 12 hr (q12hr)), 49 dogs received a low dose of pimobendan (0...
January 20, 2017: Journal of Veterinary Medical Science
S Birch, D Casamian-Sorrosal, S Fonfara, G Chanoit, C Warren-Smith
This case report describes a combination of congenital cardiopulmonary abnormalities found in a 1-year-old Labrador Retriever. To the authors' knowledge this combination of cardiopulmonary abnormalities has not been previously reported in veterinary medicine. Unilateral absence of the right pulmonary artery associated with unilateral right-sided aortopulmonary collaterals was observed. These aortopulmonary collaterals preserved the blood supply to the right lung lobes but led to left ventricular volume overload...
December 2016: Journal of Veterinary Cardiology: the Official Journal of the European Society of Veterinary Cardiology
M Yata, A J McLachlan, D J R Foster, A S Hanzlicek, N J Beijerink
INTRODUCTION: To investigate the pharmacokinetics and pharmacodynamics of oral pimobendan in conscious, healthy cats. ANIMALS: Eight healthy adult cats. MATERIALS AND METHODS: A randomised, single-blinded, crossover design was used. Two oral doses of pimobendan (0.625-mg [LD], 1.25-mg [HD]) and a control substance (3-mL water) were administered to each cat. Blood collection, echocardiography, and oscillometric blood pressure measurements were performed repeatedly for 12 h following each dose...
December 2016: Journal of Veterinary Cardiology: the Official Journal of the European Society of Veterinary Cardiology
S M Apple, G Menciotti, L Braz-Ruivo, S Crosara, J Häggström, M Borgarelli
OBJECTIVES: To describe pulmonary transit time (nPTT) and myocardial perfusion (nMP) normalised to heart rate in dogs with stable ACVIM stage C myxomatous mitral valve disease (MMVD) and to assess short-term effects of pimobendan on these variables. We hypothesised that nPTT and nMP would increase in dogs with MMVD compared with normal dogs. Additionally, we hypothesised that treatment with pimobendan would decrease nMP and nPTT in dogs with MMVD. DESIGN: Prospective, single-blind study involving 6 normal dogs and 12 dogs with MMVD...
September 2016: Australian Veterinary Journal
Marjolein Lisette den Toom, Tetyda Paulina Dobak, Els Marion Broens, Chiara Valtolina
BACKGROUND: In dogs with canine monocytic ehrlichiosis (CME), respiratory signs are uncommon and clinical and radiographic signs of interstitial pneumonia are poorly described. However, in human monocytic ehrlichiosis, respiratory signs are common and signs of interstitial pneumonia are well known. Pulmonary hypertension (PH) is classified based on the underlying disease and its treatment is aimed at reducing the clinical signs and, if possible, addressing the primary disease process...
July 7, 2016: Acta Veterinaria Scandinavica
João Brandão, Caryn A Reynolds, Hugues Beaufrère, Jacqueline Serio, Robert V Blair, Lorrie Gaschen, James G Johnson, Fabio Del Piero, Steven A Barker, Javier G Nevarez, Thomas N Tully
CASE DESCRIPTION An adult sexually intact female Harris hawk (Parabuteo unicinctus) housed at a wildlife hospital was evaluated because of acute collapse during an educational exhibition. CLINICAL FINDINGS Physical examination and hematologic analysis revealed no abnormalities; radiography revealed findings consistent with a previous tibiotarsal fracture. Coelioscopy with histologic examination and fungal culture of lung and air sac samples revealed anthracosis but no fungal infection. The hawk was discharged and temporarily removed from the education program; 1 month later, upon reintroduction into the program, it collapsed again...
July 15, 2016: Journal of the American Veterinary Medical Association
Christopher P Regan, Gary L Stump, Theodore J Detwiler, Li Chen, Hillary K Regan, David B Gilberto, Joseph J DeGeorge, Frederick J Sannajust
INTRODUCTION: There has been an increasing need to conduct investigative safety pharmacology studies to complement regulatory-required studies, particularly as it applies to a comprehensive assessment of cardiovascular (CV) risk. METHODS: We describe refined methodology using a combination of telemetry and direct signal acquisition to record concomitant peripheral hemodynamics, ECG, and left ventricular (LV) structure (LV chamber size and LV wall thickness) and function, including LV pressure-volume (PV) loops to determine load independent measures of contractility (end systolic elastance, Ees, and preload recruitable stroke work, PRSW) in conscious beagle dogs...
September 2016: Journal of Pharmacological and Toxicological Methods
Nataliya Sadekova, Ghislaine Boudreau, Benoit Jalbert, Kevin Norton
INTRODUCTION: There is a growing weight of evidence to suggest that myocardial contractility is an important parameter to assess as part of IND enabling studies in addition to standard assessments as per the ICH S7A and S7B guidelines. Historically, assessments of contractility have been limited to snap-shot echocardiography or single housed telemetry assessments of left ventricular pressure. There is a growing number of studies showing that social housing conditions in large animals are beneficial, do not impact the integrity of the data collected and improve animal welfare...
September 2016: Journal of Pharmacological and Toxicological Methods
Lewis V Buchanan, William A Warner, Susan R Arthur, Carol R Gleason, Geoff Lewen, Paul C Levesque, Michael W Gill
INTRODUCTION: Preclinical assessment for alterations in cardiac ventricular function for drug candidates has not been a focus of ICH S7b guidelines for cardiovascular safety studies, but there is growing interest given that the cardiovascular risk is associated with positive and negative inotropes. METHODS: From 2003 through 2013, 163 telemetry studies with left-ventricular function analyses were conducted in dogs and monkeys at Bristol Myers Squibb (BMS) in support for drug development programs...
July 2016: Journal of Pharmacological and Toxicological Methods
Yuichi Miyagawa, Noboru Machida, Noriko Toda, Yoshinori Tominaga, Naoyuki Takemura
Pimobendan (PIMO) can cause adverse effects, such as mitral valve degeneration, in dogs; however, it is unclear whether these effects occur in cats. Therefore, we aimed to determine whether PIMO or benazepril produces adverse cardiac effects in healthy cats. This was a blinded, randomized, prospective parallel study. Twelve cats were randomly divided into two groups of six cats, namely, an angiotensin-converting-enzyme inhibitor group that received benazepril and a PIMO group. Cats were administered their respective treatments for 506 days, and we evaluated cardiac parameters, blood biochemistry and glomerular filtration rates during that time...
August 1, 2016: Journal of Veterinary Medical Science
A C Vollmar, P R Fox
BACKGROUND: Dilated cardiomyopathy (DCM) is a common cause of morbidity and mortality in the Irish Wolfhound (IW). However, the benefit of medical treatment in IW dogs with preclinical DCM, atrial fibrillation (AF), or both has not been demonstrated. OBJECTIVES: Compare the time to develop congestive heart failure (CHF) or sudden death in IW dogs with preclinical DCM, AF, or both receiving monotherapy with pimobendan, methyldigoxin, or benazepril hydrochloride. ANIMALS: Seventy-five client-owned IW dogs...
March 2016: Journal of Veterinary Internal Medicine
P Pollesello, Z Papp, J Gy Papp
The use of inotropes for correcting hemodynamic dysfunction in patients with congestive heart failure has been described over many decades. Drugs such as cardiac glycosides, cathecolamines, phosphodiestherase inhibitors, and calcium sensitizers have been in turn proposed. However, the number of new chemical entities in this therapeutic field has been surprisingly low, and the current selection of drugs is limited. One of the paradigm shifts in the discovery for new inotropes was to focus on 'calcium sensitizers' instead of 'calcium mobilizers'...
January 15, 2016: International Journal of Cardiology
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