SCIENTIFIC PRESENTATIONS
2024 Heart Rhythm Society Meeting (Boston, Massachusetts): Attenuation of Drug-Induced QT-Prolongation in Guinea Pig Isolated Heart and Anesthetized Dog Models of Drug-Induced QT Prolongation by serum/glucocorticoid regulated kinase 1 (SGK-1) Inhibitors
2023 Keystone Symposia Meeting (Santa Fe, New Mexico): Right Ventricular Function Evaluation by Echocardiography in the Monocrotaline-Induced Pulmonary Arterial Hypertension Model
2022 American Heart Association Meeting (Chicago, Illinois): Structural and Functional Changes of the Right Ventricle in Sprague Dawley and Wistar Rat Models of Pulmonary Arterial Hypertension
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2021 American Heart Association Meeting (Boston, Massachusetts): Longitudinal Analysis Supports Reproducibility of Treatment with Sildenafil in the Semaxanib/Hypoxia Rat Model of Pulmonary Arterial Hypertension
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2021 Experimental Biology Meeting (Virtual Meeting): Angiotensin-Converting Enzyme Inhibition in a Mouse Model of Transverse Aortic Constriction with Reduced Variability of the Aortic Peak Pressure Gradient
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2020 American College of Toxicology Meeting (Austin, Texas): Validation of The Use of a Telemetry Study to Measure Hemodynamic, Electrocardiographic and Respiratory Parameters in The Conscious Dog
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2020 American Heart Association Meeting (Virtual Meeting): APD588, a Novel, Selective S1P Receptor Modular, Regulates Inflammatory Responses and Attenuates Cardiac Dysfunction Following Experimental Myocardial Infarction in Mice
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2020 Safety Pharmacology Society Meeting (Virtual Meeting): Method of Transverse Aortic Constriction in Mice with Reduced Variability of the Aortic Peak Pressure Gradient
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2019 American College of Toxicology Meeting (Phoenix, Arizona): Sildenafil versus Ambrisentan in a Rat Model of Pulmonary Arterial Hypertension
2019 German PharmTox Meeting (Stuttgart, Germany): Effect of TSN3015 on the Development of Pulmonary Hypertension in Male Sprague-Dawley Rats
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2018 Safety Pharmacology Society Meeting (Washington DC, USA): Effect of TSN3015 on the Development of Pulmonary Hypertension in Male Sprague-Dawley Rats
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2016 Safety Pharmacology Society Meeting (Vancouver, Canada): Effect of Anesthetics on Hemodynamics in Monocrotaline Pulmonary Hypertension
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2016 Safety Pharmacology Society Meeting (Vancouver, Canada): Ferric Chloride-Induced Arterial Thrombosis Model in Preclinical Drug Development
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2015 Society of Toxicology Meeting (San Diego, California): Differential Effect of Anesthetic on QT Interval Measurements in Guinea Pigs – Part 2
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2014 Society of Toxicology Meeting (Phoenix, Arizona): Effect of Anesthetic on QT Interval Measurements in Guinea Pigs
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2013 American College of Toxicology Meeting (San Antonio, Texas): PAH Induced by Semaxanib and Low Oxygen Environment: Time Course Pulmonary Artery Pressure Increases Measured by Telemetry
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2012 Transcatheter Cardiovascular Therapeutics Meeting (Miami, Florida): Veropaque, A Novel Contrast Formulation, Mitigates Contrast Induced Acute Kidney Injury
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2012 Experimental Biology Meeting (San Diego, California): Bosentan and Sildenafil Reduces PAH Induced by Semaxanib and Low Oxygen Environment
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2012 Experimental Biology Meeting (San Diego, California): Bosentan and Sildenafil Reduce Pulmonary Arterial Hypertension in Rats Induced by Semaxanib and a Low Oxygen Environment
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2012 Experimental Biology Meeting (San Diego, California): Dronedarone Effects on Atrial and Ventricular Electrophysiology in Conscious Dogs
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2008 Safety Pharmacology Society Meeting (Madison, Wisconsin): Effect of Pacing Rate and Blockade on Cardiac Refractory and His-Bundle Conduction
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CORDYNAMICS PUBLICATIONS
Comprehensive Echocardiographic Assessment of Right Ventricle Function in a Rat Model of Pulmonary Arterial Hypertension (download coming soon)
In preclinical studies, the monocrotaline (MCT) injury model in rats is widely used to evaluate drug efficacy for treating PAH. This protocol describes the echocardiographic evaluation of the RV in naïve and MCT-induced PAH rats
Data for Eli Lilly/CoLucid was published in the British Journal of Pharmacology that assessed the in vivo vascular effects of lasmitidan compared to sumatriptan. Sonomicrometry was used to determine carotid and coronary arterial diameter, along with vasoconstriction and vasodilation.
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Preclinical Studies of a Kidney Safe Iodinated Contrast Agent
In an attempt to develop a contrast agent that is less damaging to the kidneys, we have studied the effects of adding a small amount of the substituted cyclodextrin, sulfobutyl-ether-β-cyclodextrin (SBECD), to iohexol in preclinical models of renal toxicity.
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This study provides a useful model for the continued search for a safe and effective intravenous amiodarone formulation devoid of the hypotensive risk associated with the current commercial formulation.
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Intravenous amiodarone (AIV) must be administered slowly after dilution to avoid hypotension, which is due to the cosolvents polysorbate 80 and benzyl alcohol used in its formulation. PM101 is a formulation of amiodarone devoid of these cosolvents, which enables bolus administration. We evaluated any potential toxicity or exaggerated adverse cardiac electrophysiologic effects of PM101 compared with AIV and control.
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The objective of the present study was to determine whether the maintenance dose of the conventional formulation of intravenous amiodarone was associated with sustained hypotension throughout the dosing period.
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This paradigm acts as a physiologically relevant bridge between purely in vitro assays and costly, resource-intensive whole-animal studies. The model has been used extensively in experimental cardiovascular investigations and it is a widely accepted surrogate for the study of human cardiac function.
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PUBLISHED COLLABORATIONS
A nephroprotective iodinated contrast agent with cardioprotective properties: A pilot study
Neurrow Pharmaceuticals conducted a pilot study examining the putative anti-ischemic effect of Captisol Enabled-iohexol in myocardial infarction. Early data are suggesting this formulation is superior to iohexol alone with regard to preservation of cardiomyocyte integrity and preservation of cardiac function.
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We performed studies for United Therapeutics to determine whether the administration of mesenchymal stromal cell-derived exosomes could improve PAH in both mice and rats. Using both hypoxia alone and hypoxia/Sugen models, our data demonstrated improvements in both pulmonary hemodynamics and right ventricular hypertrophy after exosome administration.
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Acceleron Pharma enlisted CorDynamics to study the effects of RAP-011, a murine analog of Sotatercept, compared to sildenafil in both the monocrotaline and hypoxia-sugen models of pulmonary arterial hypertension. Note the large reductions in both mean pulmonary arterial pressure and right ventricular hypertrophy with RAP-011.
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We generated data for Xention that showed notable efficacy of XEN-R0703 with regard to increasing atrial refractoriness and reduction of atrial fibrillation inducibility in a chronic, conscious model of AF. XEN-R0703 also did not affect corrected QT interval, an indication of atrial vs. ventricular selectivity.
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Working with CoLucid Pharmaceuticals, CorDynamics studied the vascular properties of lasmitidan and sumatriptan in preclinical cardiovascular studies and compared these results with human isolated arteries. The lack of vasoconstrictive properties of lasmitidan may be a cardiovascular safety advantage compared to the triptans.
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In collaboration with Hoffman-La Roche, CorDynamics conducted studies to determine the molecular mechanism of an arrhythmia found during the course of routine toxicological assessments. The compound RO5657, a CCR5 antagonist, was discovered to have the rare liability of inducing torsades de pointes (polymorphic ventricular arrhythmia) in normal, healthy animals.
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CorDynamics collaborated with the Kalypsys study of KLYP961. KLYP961 represents an ideal tool with which to probe the physiological role of NO derived from iNOS and nNOS in human pain and inflammatory states. KLYP961 has minimal off-target activity, desirable drug like properties such as pharmacokinetic profile, CYP-450 and hERG activities. In addition, KLYP961 has efficacy in a range of pain/inflammation models both in rodents and non-human primates.
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Monocrotaline Induced Pulmonary Arterial Hypertension in Rats
In collaboration with Corridor Pharmaceuticals, CorDynamics demonstrated the novel serotonin receptor antagonist C-122 prevents monocrotaline induced pulmonary arterial hypertension in rats in a paper published in the European Journal of Pharmacology. The authors hypothesized that interfering with serotonin function may reduce the vascular remodeling and hemodynamic changes that occur in this preclinical model.
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A Small-Molecule Antagonist of HIF2a Is Efficacious in Preclinical Models of Renal Cell
Carcinoma
CorDynamics conducted studies for Peloton Therapeutics using rat telemetry to examine the cardiovascular effects of a small-molecule HIF2a antagonist, PT2385. In addition, the increased blood pressure following administration of the VEGF receptor antagonist sunitinib was detailed.
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Englerin A Agonizes the TRPC4/C5 Cation Channels to Inhibit Tumor Cell Line Proliferation
In collaboration with Novartis Pharmaceuticals, CorDynamics demonstrated the differential effects of Englerin A and B in an anesthetized rat model of cardiovascular assessment.
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Working with Lytix Biopharma, CorDynamics used telemetered rats to investigate the potential adverse effects of DTT-205 and DTT-304 – oncolytic peptides that represent a novel, promising cancer treatment strategy with activity in a broad spectrum of cancer entities including colorectal cancer (CRC).
CorDynamics conducted Langendorff isolated heart assessments along with telemetry in large species for Enanta Pharmaceuticals to interrogate the cardiovascular profile of STA-9584, a vascular disrupting agent.
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