Langendorff Rabbit Heart

The vitamin has been shown to be able to protect animals from the lethal effects of anoxia and hypoxia. Rats [189] and rabbits [190] fed on vitamin-E-supple-mented diets survived longer in hypoxia than non-supplemented animals. A similar protective effect has been demonstrated in vitro with cardiac muscle [ 167]. In hypoxic Langendorff-perfused rabbit heart, the presence of vitamin E protected the muscle from the deleterious effects of hypoxia, possibly by improving mitochondrial function [168]. However, in clinical studies, the use of vitamin E in ischaemic heart disease has met with little success [191, 192], although the results have been controversial [193]. 

The effects of hypertonic perfusion during hypoxia has been investigated in the Langendorff-perfused rabbit heart. During 60 min of control hypoxia (295 mosM), Na i rose from 22 to 100 meq kg dry weight whilst [Ca Ji rose from 347 to 1306 nM. In hearts perfused with 325 mosM buffer the increases in Na i and Ca j were reduced by 65 and 60%, respectively. Hypertonic perfusion also diminished Na" uptake after normoxic acidification by 87%. The role of creatine kinase (CK), high energy phosphates and Ca -influx in... 

The effects of L-arginine on energy metabolism and coronary vessel function of ischaemic and reperfused rabbit myocardium have been investigated with P NMR. Langendorff-perfused rabbit hearts were subjected to 180 min of ischaemia at 15° and then reperfused for 60 min at 37°. When L-arginine was added to the cardioplegia solution, coronary flow rate during reperfusion, ATP and PCr were improved. 

The protective effects of the Mn(ii)-based SOD mimics against myocardial ischemia/reperfusion injury in the isolated rabbit heart and monkey heart have been investigated. Kilgore et subjected Langendorff perfused, isolated rabbit hearts to a 30 minute period of global ischemia followed by a 45 minute period of reperfusion. Upon reperfusion, an increase in left ventricular end-diastolic pressure occurred, which was attenuated when the hearts were perfused with 20/.iM SC-52608. Perfusion of SC-52608 also inhibited the release of creatine kinase and intracellular potassium, and reduced the extent of antibody binding to the intracellular protein myosin which occurs upon reperfusion of the ischemic heart. These studies indicated that SC-52608 is cardioprotective to the reperfused, ischemic isolated rabbit heart. 

APPLICATION Myocardial cell action potentials collected from a Langendorff setup of an isolated rabbit heart experiment have been fouttd to exhibit chaotic behavior. Two different cardiac cell action potential waveforms are illustrated in Fig. 18.10 correspotuling to ventricidar fibrillation (VF) in (a) and normal struts rhythm (NSR) in (b). The corresponding frequerKy spectrum is shown inFig. 18.11. VF certainly shows chaotic characteristics in Fig. 18.11a, whereas NSR shows distinct spectral lines in Fig. 18.11b, indicating the presence of deterministic components. Using the calculated correlation dimensions for the two different action potentials (VF = 5.629, NSR = 2.704), the embedding dimension is m = 6 for VF. The projections of the trajectories for VF in a three-... 

Isolated Hearts Similarly, an entire heart can be removed from an animal donor (e.g., rabbit) and studied in isolation via Langendorff perfusion using different modes of contraction such as isovolumetric (Qu et al., 2013) or working heart under various conditions of preload and afterload (Werchan and McDonough, 1987). This approach shares many of the characteristics of the isolated tissue approach, including the need for technical expertise to run... 

Lawrence CL, Bridgland-Taylor MH, Pollard CE, Hammond TG, Valentin JP (2006). A rabbit Langendorff heart proarrhythmia model predictive value for chnical identification of Torsades de Pointes. BrJ Pharmacol 149(7) 845-860. 

Cardiac SP in vivo methods primarily use conscious telemetered animals to assess the effects of the test item on the cardiovascular system. Variables that are recorded in the dog include blood pressure, heart rate and ECG (see Authier et al. 2015). Complementary studies, usually non-GLP in namre, include a number of in vitro assays that have been well characterised with utility in the safety profiling of an NCE. These assays include assessment of drug effects in the isolated guinea pig right atrium preparation, rabbit Purkmje fibre preparation, the isolated Langendorff heart and the isolated wedge preparation. Each assay will be briefly discussed. 

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