Isolated-heart studies

Livers isolated from rats or mice may conveniently be studied by NMR spectroscopy. The organs are perfused through the portal vein with solutions similar to those described for isolated heart studies (supplemented with albumin). The methods described above for and Na NMR spectroscopy have been successfully applied to the isolated liver. The NMR spectrum of the isolated liver differs from the heart spectrum in that it lacks the PCr peak observed in spectra obtained from hearts. This technique has been utilized to examine various aspects of ethanol metabolism in the liver, including the effects of chronic ethanol exposure on subsequent acute ethanol exposure and hypoxia. These studies revealed that chronic ethanol exposure caused an adaptation in the liver such that it becomes more resistant to acute ethanol exposure and also to hypoxia. 

Cd has also been shown to induce cardiac damage in experimental settings by two possible mechanisms (i) disruption of tissue stmcture and integrity (ii) effects on cardiac conduction (reviewed in [5]). These effects were thought to be related to (i) decreased high-energy phosphate storage in the myocardium, (ii) reduced myocardial contractility, (iii) diminished excitability of the cardiac conduction system, and (iv) a reduction in coronary blood flow by Cd in isolated heart studies due to direct actions on the coronary vasculature [340]. 

The possible role of cellular glutathione status in the controlling sarcolemmal protein activity has been addressed by studying the effect of GSH, GSSG and several other thiol and disulphide compounds on Na/K ATPase activity using (1) an isolated bovine ventricular Na/K ATPase preparation (2) crude sarcolemmal preparations (biochemical studies) (c) Langendorff-perfiised isolated hearts (cytochemical studies) and (4) isolated ventricular myocytes (electrophysiologjcal studies). 

Abstract Recently, we have investigated Aconitum cochleare Woroschin and obtained three new alkaloids cochleareine, acoleareine from the aerial parts of the plant and cochleareinine from the roots. Cochlearenine exhibited antioxidant activity against DPPH free radical scavenging assay. The cardio active effect of has also have been studied on isolated heart preparations. 

More recent studies continue to support the unique antifibrillatory activity of bretylium. Kowey et al. [38] have shown that bretylium prevented spontaneous VF and decreased the effects on VF threshold in a feline myocardial infarction model. They attributed this beneficial effect to a decrease in the dispersion of refractoriness between normal and ischaemic regions of the heart. In contrast, clofilium (14, see below), which had little effect on dispersion of refractoriness after coronary occlusion, was unable to prevent spontaneous VF. Similar results were seen in isolated tissue studies with canine subendocardial Purkinje fibres and ventricular muscle which contained both normal and ischaemic regions [39]. In these studies bretylium caused a smaller increase in dispersion of refractoriness in subendocardial Purkinje fibres than either sotalol or clofilium. In ventricular muscle tissue, bretylium decreased dispersion while sotalol and clofilium increased dispersion of refractoriness. 

Additionally, the isolated heart can be used to measure chronotropic or inotropic effects. There are several additional ex vivo assays like the sinoatrial node preparation [76], left ventricular wedge preparation [77] available which address specific questions. All of the ex vivo studies mentioned above with the... 

From A. membranaceous, Wang [145] obtained a saponin-enriched extract and studied its effect on the isolated heart of rats. At doses of more than 50 ftg/ml, the extract showed a positive inotropic effect, which turned negative at 30 p.g/ml. The mechanism was similar to that of cardiotonic glycosides. By bioactivity-guided fractionation, the active constituent with positive inotropic activity was isolated and characterized as astragaloside IV [146]. 

Studies of Arrhythmogenic Effects in Isolated Heart Preparations... 

The effect of benzene on the respiration of isolated heart mitochondria was studied by Stolze and Nohl (1994). Respiratory control and ATP/oxygen values decreased in the presence of benzene at 100 pM. A concomitant increase in superoxide radical formation was observed. This suggests a mechanism for benzene-mediated damage to cardiovascular tissue and other tissues as well. 

AH studies of the cardiotoxic effects of local anesthetics on the isolated heart pubhshed from 1981 to 2001 have been reviewed (4). Thirteen studies were identified, all of which studied bupivacaine, either alone or compared with other local anesthetics. The general conclusions were ... 

Consistent with this, AB KO RV trabeculae had no significant inotropic response to PE, indicating that the D was not involved in inotropy (16). However, in studies of the AB KO isolated heart, we were surprised to find in the WT mouse heart that PE caused a PIE, the first report of this in the mouse. There was a transient NIE, then a sustained PIE, with an increase almost 20% over control. 

Different experimental techniques have been also used to investigate ischemia-reperfusion injury. Table 2. Experimental models of isolated hearts cannot consider the contribution of blood components or neurohormonal changes as this occurs in in vivo studies. However, these studies are able to dissect potential underlying mechanisms of the ischemic injury. The mode of perfusion (working heart vs Langendorff mode or constant flow vs constant pressure), the use of pacing, the composition of the perfusate and the end-points chosen to assess myocardial injury (arrhythmias, functional recovery... 

The cardiac safety of nomlfensin was established by measurements of cardiac conduction in depressed patients receiving therapeutic doses over 3 weeks, and it was less toxic than doxepin or amitriptyline In Isolated hearts. 3 Nomlfensin Inhibited NA uptake in the same way as TCA but its principal actions may be on dopaminergic (DA) systems, both as an uptake inhibitor and as an agonist.5 The metabolites (, Ri=0H, R2=H 2c, Ri= OCH3, R2=0H Ri=0H, R2=OCH3) Inhibit the uptake of DA and 5-HT, but another potential metabolite, the catechol (2e, Rx=R2=0H) is a potent DA agonist in behavioral and neurochemical studies. 5 However, the beneficial effects of 7 in parkinsonism may be due to its improvement of depressive s3nnptoms. 6... 

It was reported35 that morphine does not act as a S3rm-patholytic on the isolated heart nor does it alter catecholamine levels or the response of the heart to sympathomimetic amines. On the other hand, iu vivo experiments in the dog3° reveal that morphine increased contractile force. This careful study revealed that the improved ventricular performance induced by morphine is indirect and probably the result of sympathoadrenal discharge. 

The pharmacological properties of nitrofurazone and nitrofurantoin were investigated by several workers . The experimental studies with various kinds of animals showed some pharmacological properties similar to those of guanofuracin hydrochloride and panfuran hydrochloride. As test devices isolated hearts of frogs, blood vessels of toads, respiration and blood pressure rates of rabbits, the central nervous system of frogs and mice, and red cell counts of rabbits were used. The results are summarized in Table 6.19. 

Studies of analogue antagonism were foreshadowed by the London work of Sidney Ringer (1883) who found, from a helper s error which he was quick to interpret, that the sodium (cations) in a solution of sodium chloride could not maintain the beat of an isolated heart unless balanced by calcium and potassium. As a result of this work, the physiologically balanced solutions, named after Ringer, Locke and Tyrode, were developed. 

A.J. de Bold, H.B. Borenstein, A.T. Veress, H.A. Sonnenberg, A rapid and potent natriuretic response to intravenous injection of atrial miocardial extracts in rats. Life Sci. 28 89-94 (1981) A.J. de Bold, Atrial natriuretic factor of the rat heart. Studies on isolation and properties. Proc. Soc. Exptl. Biol. Med. 1982 133-138... 

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