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The role of the anaesthetised guinea-pig in the preclinical cardiac safety evaluation of drug candidate compounds.
A single in vivo screen provides a significant amount of information pertaining to the cardiovascular risk of drug candidates, ultimately strengthening strategies addressing cardiovascular-mediated compound attrition and drug withdrawal. Expand
Arrhythmogenic activities of antiarrhythmic drugs in conscious hypokalemic dogs with atrioventricular block: comparison between quinidine, lidocaine, flecainide, propranolol and sotalol.
Quinidine and sotalol, but not flecainide, propranolol or lidocaine, were the only drugs associated with proarrhythmic events in the present study, suggesting that QT-dependent arrhythmogenic effects of drugs can be reliably evaluated in conscious hypokalemic dogs with complete atrioventricular block. Expand
Functional assessments in repeat-dose toxicity studies: the art of the possible
Functional measurements can be incorporated into repeat-dose toxicity studies, either routinely or on an ad hoc basis, and are entirely achievable if functional measurements are relatively unobtrusive, both with respect to the animals and to the toxicology study itself. Expand
Serotonin receptor blockade improves distal perfusion after lower limb ischemia in the fatty Zucker rat.
The results suggest that the recruitment of collateral vessels after the induction of hindlimb ischemia is significantly impaired in obese fa/fa Zucker rats due to a persistent vasoconstriction mediated by 5-HT and involving stimulation of 5- HT(1B) and/or5-HT(2A) receptors. Expand
Detecting drug-induced prolongation of the QRS complex: new insights for cardiac safety assessment.
Electrocardiogram recordings during elevated HR, not considered during routine analysis optimised for detecting QT prolongation, can be used to sensitise the detection of QRS prolongation. Expand
Delayed neutralization of interferon-&ggr; prevents lethality in primate Gram-negative bacteremic shock
Objective:Whether anticytokine therapies have a place in the treatment of severe sepsis and septic shock remains a question. Although a number of preclinical studies have shown efficacy in primateExpand
Mechanisms of pulmonary edema induced by an organophosphorus compound in anesthetized dogs.
It is suggested that VX injection induces an increase in pulmonary capillary permeability which may lead to a high-permeability edema. Expand
[Sotalol-induced torsades de pointe in the conscious dog with atrioventricular block. Role of hypokalemia].
The pro-arrhythmic effects of sotalol were very frequent on this experimental model, but hypokalaemia was not necessary for torsades de pointe to occur. Expand
It is demonstrated for the first time in primates that overwhelming gram-negative bacteremia produces an early and profound lymphocyte death that occurs through multiple cell death pathways. Expand
Methods and limitations of an experimental model of long QT syndrome.
An experimental model of the long QT syndrome has been developed in conscious dogs and is suitable for screening the bradycardia-dependent proarrhythmic effects of drugs and for studying the electrophysiology of "torsades de pointes". Expand