Assessment of the pharmacological effects of inotropic drugs on left ventricular pressure and contractility: An evaluation of the QA interval as an indirect indicator of cardiac inotropism

Journal of Pharmacological and Toxicological Methods

Volumn 60, Issue 2, 2009, Pages 193-197

  Norton, K ^a   Iacono, G ^a   Vezina, M ^a  

^a CHARLES RIVER LABORATORIES   (United States)

Author keywords

Beagle dog; Inotropic effect; Left ventricular contractility; Left ventricular pressure; QA interval

Indexed keywords

ATENOLOL; PIMOBENDAN;

ANIMAL EXPERIMENT; ARTERIAL PRESSURE; ARTICLE; BLOOD PRESSURE MEASUREMENT; CARDIOVASCULAR PARAMETERS; CONTROLLED STUDY; DOG; DRUG SAFETY; ELECTROCARDIOGRAM; HEART LEFT VENTRICLE CONTRACTILITY; HEART LEFT VENTRICLE DP-DT; HEART LEFT VENTRICLE PRESSURE; HEART RATE; INOTROPISM; MALE; NONHUMAN; QA INTERVAL; SINGLE DRUG DOSE; TELEMETRY;

ADRENERGIC BETA-ANTAGONISTS; ANIMALS; ATENOLOL; BLOOD PRESSURE; CARDIOTONIC AGENTS; DOGS; DRUG EVALUATION, PRECLINICAL; MALE; MODELS, ANIMAL; MYOCARDIAL CONTRACTION; PYRIDAZINES; VENTRICULAR FUNCTION, LEFT;

CANIS FAMILIARIS;

EID: 68549130485     PISSN: 10568719     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.vascn.2009.05.008     Document Type: Article

References (15)

1. Anon., 2000. Anon. (2000, November 16). ICHS7A: Safety pharmacology studies for human pharmaceuticals. CPMP/ICH/539/00. London.
2. Anon., 2005a. Anon., ICH S7B: The nonclinical evaluation of the potential for delayed ventricular repolarization (QT interval prolongation) by human pharmaceuticals (2005, May 25) London. CPMP/ICH/423/02.
3. Anon., 2005b. Anon., ICH E14: The clinical evaluation of QT/QTc interval prolongation and proarrhythmic potential for non-antiarrhythmic drugs (2005, May 25) London. CPMP/ICH/2/04.
4. Cambridge D., and Whiting M. Evaluation of the QA interval as an index of cardiac contractility in anesthesised dogs: Responses to change in cardiac loading and heart rate. Cardiovascular Research 20 6 (1986) 444-450
5. Fermini B., and Fossa A.A. The impact of drug-induced QT interval prolongation on drug discovery and development. Nature Reviews - Drug Discovery 2 6 (2003) 439-447
6. Haushalter T.M., Friedrichs G.S., Reynolds D.L., Barecki-Roach M., Pastino G., Hayes R., and Bass A.S. The cardiovascular and pharmacokinetic profile of dofetilide in conscious telemetered beagle dogs and cynomolgus monkeys. British Journal of Pharmacology 154 (2005) 1457-1464
7. Markert M., Klumpp A., Trautmann T., Mayer K., Stubhan M., and Guth B. The value added by measuring myocardial contractility 'in vivo' in safety pharmacological profiling of drug candidates. Journal of Pharmacological and Toxicological Methods 56 2 (2007) 203-211
8. McMahon N., Pollard C.E., Hammond T.G., and Valentin J.P. Cardiovascular safety pharmacology. In: Sietsema W.K., and Schwen R. (Eds). Nonclinical drug safety assessment - Practical considerations for successful registration (2007), FDA News 87-123
9. Moors J., Philip K., Harmer A., Lainee P., and Valentin J.P. Incidence of cardiac contractility issues in safety pharmacology studies: Is the core battery sufficient. The Society of Safety Pharmacology annual meeting (2007) (Abstract)
10. Prior H., McMahon N., El-Amrani F., Martel E., Richard S., and Valentin J.P. The QA interval as an indirect measure of inotropic state in conscious dogs. Journal of Pharmacological and Toxicological Methods 56 2 (2008) 51
11. Spence S., Super K., Hoe C.H., and Coleman J. The heart rate corrected QT interval of conscious beagle dogs: A formula based on analysis of covariance. Toxicological Sciences 45 (1998) 247-258
12. 2+ channel blocker AH-1058 in conscious dogs assessed by telemetry. European Journal of Pharmacology 413 1 (2001) 101-108
13. Tontodonati M., Fasdelli N., Moscardo E., Giarola A., and Dorigatti R. A canine model used to simultaneously assess potential neurobehavioural and cardiovascular effects of candidate drugs. Journal of Pharmacological and Toxicological Methods 56 2 (2007) 265-275
14. Valentin J.P., and Hammond T. Safety and secondary pharmacology: Successes, threats, challenges and opportunities. Journal of Pharmacological and Toxicological Methods 58 (2008) 77-87
15. Van de Water A., Verheyen J., Xhonneux R., and Reneman R.S. An improved method to correct the QT interval of the electrocardiogram for changes in heart rate. Journal of Pharmacological Methods 22 3 (1989, Nov) 207-217