Cardiovascular system components

The development of cardiac assist devices and other instrumentation and components which come in contact with the cardiovascular system requires materials which will perform in a physiological environment. One particularly difficult application is the diaphragm for blood pumps, which requires an elastomer to undergo cyclic deformation and/or flexing while in contact with blood. 

The system that circulates blood is the cardiovascular system, shown in schematic form in Figure 9.1. It consists of two major components the muscular part of the heart, called the myocardium, and the network of blood vessels composed of arteries, veins, and capillaries. Blood circulation is the body s transportation system that supplies tissues with the oxygen, nutrients and their metabolites, and hormones that they need for their function. Blood carries carbon dioxide, encapsulated dead cell matter, and other wastes away from tissues. Circulating blood is crucial to maintaining body homeostasis, with temperature, pH, and other crucial parameters kept within the narrow ranges required for good health. A number of toxicants have adverse effects on the cardiovascular system. 

In the cardiovascular system, leptin has been demonstrated to activate components of the MAPK pathways. In cultured neonatal myocytes, ERK1/2 and p38, but not JNK, were activated by leptin inhibiting ERK had no effect, while inhibition of p38 completely inhibited leptin-induced cardiomyocyte hypertrophy (Rajapurohitam et al. 2003). Leptin has also been shown to induce hyperplasia in the immortalized atrial HL-1 cell line via an ERK-dependent pathway (Tajmir et al. 

Heme oxygenase-1 is inducible and a number of compounds have been identified which induce it so as to produce carbon monoxide, biliverdin/bilirubin and Fe2+/ferritin [12]. These include aspirin, statins, curcumin (a component of turmeric) and resveratrol (a component of red wine). The induction of heme oxygenase takes many hours so that such treatments are applicable to chronic conditions. Aspirin and statins are now prescribed for the cardiovascular system but the significance of the heme oxygenase is unproven. The compounds that are catabolised to give CO provide an alternative procedure. 

The u.se of agents that directly affect the peripheral component of the sympathetic nervous system represents an important approach to the treatment of hypertension. A second approach to modifying sympathetic influence on the conllo-vascular. system is through inhibition or reduction of CNS control of blixxl pressure. Several widely used medicalirss act by stimulating receptors, which in the CNS reducer sympathetic outflow to the cardiovascular system and produces a hypotensive effect. 

Squalene and phytosterols are components present in the unsaponifiable lipid fraction of foods (as tocopherols). Squalene is an intermediary in cholesterol biosynthesis, and 33.9-58.4 mg/100 g of it was found in the lipid fraction of quinoa (Jahaniaval et al., 2000 Ryan et ah, 2007) squalene is the biochemical precursor of the whole family of steroids, and besides their effective antioxidant activity, tocotrienols have other important functions, in particular in maintaining a healthy cardiovascular system and a possible role in protection against cancer (Nesaretnam, 2008). Squalene is used as a bactericide and as an intermediate in many pharmaceuticals, organic coloring materials, rubber chemicals, and surface-active agents (Ahamed et ah, 1998). 

This book is a self-contained introduction to, and exposition of, the field of biophar-maceutical cardiovascular safety. While drugs for cardiovascular diseases or conditions of clinical concern are expected to affect the cardiovascular system, drugs for other indications are not. However, there is always the possibility that a noncardio-vascular drug can exert a deleterious influence on one or more parts of the cardiovascular system, and, while rare, some drug-induced cardiac adverse events can be fatal. The field of cardiovascular safety, of which proarrhythmic cardiac safety is an important component, has therefore assumed considerable importance in contemporary drug development and therapeutic use. Not everyone needs to be an expert in cardiovascular safety (and this book by itself does not presume to make anyone an expert), but everyone can benefit from a fundamental knowledge of the field. 

Major advances are being made in the field of cardiac TE. So far, it is possible to engineer all the components of the cardiovascular system including blood vessels, heart valves, and cardiac muscle by using bioresorbable polymers. Regarding cardiac muscle repair, this chapter has reviewed how bioresorbable polymers administered either alone or as delivery vehicles have shown positive results such as cardiac function improvement, infarct size reduction, and increase in neovascularization in precUnical studies. 

FMD and blood pressure have been often used for the evaluation of the effect of the dietary intake of polyphenols on the protection of the cardiovascular system. Indeed, the basal FMD is increased in healthy subjects after two glasses of red wine with or without alcohol [100] or after consumption of 3 ml/kg of red wine [101]. Similarly, intake of red wine has been shown to restore a normal endothelial function in hypercholesterolemic patients with impaired FMD [99,102]. A study by Papamichael et al. has also shown that acute intake of two glasses of red wine with or without alcohol is able to reduce the endothelial dysfunction induced by the smoking of one cigarette by healthy nonsmokers [103], Moreover, acute intake of two glasses of red wine without alcohol improves FMD in patients with coronary artery disease, while intake of regular red wine was less effective, suggesting that the beneficial effect is due to the polyphenol content rather than the alcohol component of red wines [104]. 

In order to analyze the functional coupling between the heart and the blood vessels, we will use a model in which the cardiovascular system has been reduced to its simplest components (Levy, 1979 Berne and Levy, 1981). The model consists of a pump, an elastic arterial system, a peripheral resistance (/ ), and an elastic venous system (Figure 1). The relative ease of analysis of the interactions among the components of this simplified model permits the elucidation of certain basic principles. For many purposes the model is much too simple and potentially misleading. For such purposes, more complicated models must be used, such as those developed by Grodins and his coworkers (1959,1960), Sagawa (1972), and Guyton et al. (1973). 

Placental membrane, cardiovascular system, lung, muscle (endomysium), secondary component of many tissues... 

Intra-arterial catheters have been used for different objectives, such as the placement of other devices like stents, the delivery of drugs to various targets in the cardiovascular system and the delivery of embolic materials to close arterial-venous fistulas. Drug therapy has also been combined with catheter ablation, pacemakers and cardioverter defibrillators in order to treat arrhythmias. On the other hand, implants for the reconstruction or functional replacement of cardiovascular components have been combined with drugs to prevent thrombosis. Finally, drugs to avoid restenosis have been widely employed in different devices such as drug-eluting stents. 

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