Heart models

Today s heart models do not yet possess the power to solve the inverse problem. They do, however, aid the understanding and interpretation of the EGG by repeatedly solving forward problems to study the effects of cellular modifications on the calculated ECG. Model reconstruction of a normal ECG is therefore a necessary first step towards developing a better understanding of the information hidden in it. Figure 8.3(a) illustrates this. 

Valentin, J.P., Hoffmann, P., De Clerck, F., Hammond, T.G., and Hondeghem, L., Review of the predictive value of the Langendorff heart model (Screenit system) in assessing the proar-rhythmic potential of drugs, /. Pharmacol. Toxicol. Methods, 49, 171-181, 2004. 

Rhodes CG, Camici PG, Taegtmeyer H, Doenst T. Variability of the lumped constant for [18F]2-deoxy-2-fluoroglucose and the experimental isolated rat heart model clinical perspectives for the measurement of myocardial tissue viability in humans. Circulation 1999 99 1275-1276... 

Kobayashi T Hamano K, Li TS, et al. Enhancement of angiogenesis by the implantation of self bone marrow cells in a rat ischemic heart model, J Surg Res 2000 89(2) I 89-195. 

Cellular sources of oxy radical and isolated heart models... 

The best way to prove the existence of the hydroxyl radical is to perform kinetic competition experiments with hydroxyl-radical scavengers [125]. Using the kinetic criterion, we can also exclude the intermediacy of the ferryl oxidant. However, such experiments in isolated heart models are, in practice, very difficult. 

ESR parameters of PBN adducts formed in various reperfusion heart models of myocardial ischemia and... 

Finally, spin trapping may also be used to assess the interaction between oxy radicals formed in the myocardium and nitric oxide released by the vascular endothelium in isolated rat and rabbit heart models. 

Heavner JE. Cardiac toxicity of local anesthetics in the intact isolated heart model a review. Reg Anesth Pain Med 2002 27(6) 545-55. 

Verma DD et al (2006) ATP-loaded immunoKposomes specific for cardiac myosin provide improved protection of the mechanical functions of myocardium from global ischemia in an isolated rat heart model. J Drug Target 14 273-280... 

Lan0endorff perfused isolated hearts. The Langendorff isolated perfused heart model is used to demonstrate adult ischemic myocardial preservation (24). 

In the coronary artery-occluded Langendorff rat heart model, irreversible injury occurred within 20 min of ischemia (28). Disruption of the sarcolemma was observed in canine hearts subjected to 15(29, 30) to 20 min of coronary occlusion and reperfusion (31). 

ATP cannot be effectively delivered to most tissues including the ischemic myocardium without protection from degradation by plasma endonucleotidases. However, it has been established that ATP can be delivered to various tissues by its encapsulation within liposomal preparations. We describe here, the materials needed and methods used to optimize the encapsulation of ATP in liposomes, enhance their effectiveness by increasing their circulation time and target injured myocardial cells with Uposomal siufece anti-myosin antibody. Additionally, we outline methods for ex vivo studies of these ATP liposomal preparations in an isolated ischemic rat heart model and for in vivo studies of rabbits with an induced myocardial infarction. The expectation is that these methods will provide a basis for continued studies of effective ways to deliver energy substrates to the ischemic myocardium. 

We describe here, the materials needed and methods used to optimize encapsulation of ATP in liposomes, enhance their effectiveness by increasing their circulation time and target injured myocardial cells with liposomal surface anti-myosin antibody. Additionally, we outline methods for ex vivo studies in an isolated ischemic rat heart model and for in vivo studies of rabbits with an induced myocardial infarction. 

Measuring Protection of the Systolic and Diastolic Functions of the Myocardium in Isolated Rat Heart Model (Fig. 3)... 

Figure 5. A, Schematic of a Largerdortf perfused rat heart model. Retrograde perfusion is established through the aorta. Perfusate oxygenated with 95% O, and 5% CO, is circulated by a peristaltic pump and the flow can be adjusted. Left ventricular pressure is monitored Ihrough a balloon which is inserted into the empty left ventricle. Heart rhythm is controlled by pacing.

C. Left ventricular pressure recording of a perfused rat heart model of zero-flow global ischemia and reperfusion. A progressive increase in LVDP occurs at reperfusion. This corresponds to myocardial stunning (data from our laboratory). 

Endothelin-1 is a potent vasoconstrictor peptide derived from endothelial cells.100 Its physiological function is mediated by two receptors the ET-A and ET-B. Table 1. Figure 11. ET-A and ET-B receptors are located in vascular smooth muscle and their activation causes vasoconstriction, whereas ET-B receptor is also located in the endothelium and its activation results in vasodilation by increasing nitric oxide or prostacyclin. Endothelin is released following myocardial ischemia and reperfusion. Endothelin reduces infarct size in a perfused rat heart model of ischemia and reperfusion through activation of protein kinase C and KATp channel.101 Furthermore, in neonatal rat ventricular myocytes, endothelin is shown to activate the calcineurin-NFAT (nuclear factor of activated cells) pathways and enhance the expression of Bcl-2.102 However, endogenous blockade of endothelin at the level of the ET-A receptor reduced infarct size in a pig model of coronary occlusion and reperfusion.103... 

Prostacyclin is increased in response to ischemia and reperfusion through activation of the cyclooxygenase-2 pathway. Inhibition of cyclooxygenase-2 by celecoxib or meloxicam resulted in a concentration dependent exacerbation of the myocardial dysfunction and damage in a perfused rabbit heart model of ischemia and reperfusion, indicating a cardioprotective role for prostacyclin.104... 

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