The evaluation of drug-induced changes in left ventricular function in pentobarbital-anesthetized dogs
| Autor: | James S. Polakowski, Scott W. Mittelstadt, Brett R. Herzberg, Yevgeniya E. Koshman, Terese R. Seifert |
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| Rok vydání: | 2018 |
| Předmět: |
Male
Inotrope medicine.medical_specialty Antifungal Agents Cardiotonic Agents Heart Ventricles Drug Evaluation Preclinical Diastole Hemodynamics Blood Pressure 030204 cardiovascular system & hematology Toxicology 030226 pharmacology & pharmacy Ventricular Function Left Amrinone Contractility Electrocardiography 03 medical and health sciences Dogs 0302 clinical medicine Internal medicine medicine Animals Hypnotics and Sedatives Anesthesia Pentobarbital Pharmacology business.industry Atenolol Adrenergic beta-1 Receptor Antagonists Myocardial Contraction Blood pressure Pimobendan Depression Chemical Models Animal Cardiology business medicine.drug |
| Zdroj: | Journal of Pharmacological and Toxicological Methods. 91:27-35 |
| ISSN: | 1056-8719 |
| Popis: | Introduction The goal of this study was to determine whether assessment of myocardial contractility and hemodynamics in an anesthetized dog model, could consistently detect drug-induced changes in the inotropic state of the heart using drugs known to have clinically relevant positive and negative effects on myocardial contractility. Methods Derived parameters included: diastolic, systolic and mean arterial BP, peak systolic LVP, HR, end-diastolic LVP, and LVdP/dtmax as the primary contractility index. Results These results demonstrate that statistically significant increases (amrinone and pimobendan) and decreases (atenolol and itraconazole) in left ventricular dP/dtmax were observed at clinically relevant exposures. Discussion The analysis from the current study supports the strategic use of the anesthetized dog model early in the drug Discovery process for a comprehensive cardiovascular evaluation that can include left ventricular dP/dtmax with good translation to human. |
| Databáze: | OpenAIRE |
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