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INTRODUCTION The dog is frequently used for cardiovascular safety pharmacology and for toxicology studies, but is not often used for central nervous system (CNS) safety pharmacology purposes. We have therefore examined the electroencephalogram (EEG) in conscious dogs by means of radio-telemetry methods using the proconvulsant agent pentylenetetrazole (PTZ)(More)
Postural-change-induced (orthostatic) hypotension is defined as an excessive drop in arterial blood pressure occurring when moving toward an upright position. This side effect, which may limit the therapeutic use of some agents, can occur with drugs, such as adrenoceptor blockers and vasodilators, that dampen sympathetic reflex activity. Described in this(More)
The protocols described in this unit are used to assess the effects of new chemical entities on arrhythmias in the guinea pig. In the anesthetized guinea pig, arrhythmias are induced by a slow intravenous infusion of digoxin, which provokes extrasystoles, ventricular tachyarrhythmias, and ultimately cardiac arrest. Imipramine precipitates the occurrence of(More)
Abnormalities of cardiac rhythm are one of the most common clinical problems in cardiology and arise as the result of either disorders of cardiac impulse formation or conduction, or a combination of both. It has been established that some classes of drugs, such as tricyclic antidepressants (e.g., imipramine), cardiac glycosides (e.g., digoxin), and Class I(More)
Fatal cardiac arrhythmias, known as torsades de pointes, can occur with a wide variety of medicinal drugs and are associated with prolongation of the QT interval. This review critically evaluates the major strategies for assessing QT prolongation risk: ion channel studies, in vitro cardiac electrophysiology, and in vivo cardiac electrophysiology and(More)
Cardiomyopathic Syrian hamsters (Bio TO-2 dilated strain) constitute an animal model of congestive heart failure, which progressively develops an alteration of cardiac function leading to decreased arterial blood pressure and musculo-cutaneous blood flow associated with a complex process of cardiac remodeling including left ventricle dilation, wall(More)
Prulifloxacin, a new thiazeto-quinoline derivative with antibiotic properties, was evaluated for cardiac risk both in vitro on the ether-à-go-go-related gene (HERG) K+ channel, and in vivo in the conscious dog monitored by telemetry. HERG current was measured from stably transfected human embryonic kidney (HEK) 293 cells by means of the patch-clamp(More)
In this study, we investigated the effect of a high n-3 fatty acid diet (eicosapentaenoic and docosahexaenoic acids) in Zucker obese and lean rats on blood pressure in association with physiological parameters, serum biochemistry and oxidative stress analysis. After 150 days of treatment, dietary fish oil supplementation in Zucker obese rats (9 months of(More)
Medicinal products that prolong cardiac repolarization unintentionally, as assessed in terms of prolongation of the QT interval of the electrocardiogram, may trigger a potentially fatal arrhythmia called torsade de pointe (TDP). This lethal risk necessitates a detailed preclinical evaluation before initiating clinical trials. There are two different and(More)
The protocols described in this unit are used to assess the effects of new chemical entities on hypertension in conscious rats. In the spontaneously hypertensive rat (SHR) model, the results obtained with the reference compounds clonidine, prazosin, propranolol, and captopril are provided for illustration. All compounds demonstrate antihypertensive(More)