Heart and

Contract JAo. N01 -HH-8-1388, National Heart, Lung and Blood Institute, Division of Heart and Vascular Diseases, Bethesda, Md. 

Copper. AH human tissues contain copper. The highest amounts are found in the Hver, brain, heart, and kidney (102). In blood, plasma and erythrocytes contain almost equal amounts of copper, ie, ca 110 and 115 mg/100 mL, respectively. 

The isotope plutonium-238 [13981 -16-3] Pu, is of technical importance because of the high heat that accompanies its radioactive decay. This isotope has been and is being used as fuel in small terrestrial and space nuclear-powered sources (3,4). Tu-based radioisotope thermal generator systems dehvered 7 W/kg and cost 120,000/W in 1991 (3). For some time, %Pu was considered to be the most promising power source for the radioisotope-powered artificial heart and for cardiovascular pacemakers. Usage of plutonium was discontinued, however, after it was determined that adequate elimination of penetrating radiation was uncertain (5) (see PROSTHETIC AND BIOMEDICAL devices). 

Deriva.tives, The most important derivatives of 1,2,3,4-benzenetetrol are the ubiquiaones, eg, coenzyme Q, which are dimethoxytoluquiaones with polyisoprenoid side chains (61). They occur ia plants and animals. Mice with hereditary muscular dystrophy have a deficiency of coenzyme Q ia their heart and hind leg muscles. Therapeutic adrninistration of coenzyme Q /7339-63-5] produces physical improvement and a significantly prolonged lifespan (212). Coenzyme Q also has been used to treat deafness when adrninistered either orally or parenteraHy (213). 

One of the more intriguing cardiovascular developments is cardiomyoplasty where implantable technologies are blended with another part of the body to take over for a diseased heart. One company, Medtronic, in close collaboration with surgeons, has developed a cardiomyoplasty system to accompany a technique of wrapping back muscle around a diseased heart which can no longer adequately pump. A combination pacemaker and neurological device senses the electrical activity of the heart and correspondingly trains and stimulates the dorsal muscle to cause the defective heart to contract and pump blood. Over 50 implants have been performed to date. 

Toxicity. The toxicity of barium compounds depends on solubility (47—49). The free ion is readily absorbed from the lung and gastrointestinal tract. The mammalian intestinal mucosa is highly permeable to Ba " ions and is involved in the rapid flow of soluble barium salts into the blood. Barium is also deposited in the muscles where it remains for the first 30 h and then is slowly removed from the site (50). Very Httle is retained by the fiver, kidneys, or spleen and practically none by the brain, heart, and hair. 

The Cardiac Cycle. The heart (Eig. lb) performs its function as a pump as a result of a rhythmical spread of a wave of excitation (depolarization) that excites the atrial and ventricular muscle masses to contract sequentially. Maximum pump efficiency occurs when the atrial or ventricular muscle masses contract synchronously (see Eig. 1). The wave of excitation begins with the generation of electrical impulses within the SA node and spreads through the atria. The SA node is referred to as the pacemaker of the heart and exhibits automaticity, ie, it depolarizes and repolarizes spontaneously. The wave then excites sequentially the AV node the bundle of His, ie, the penetrating portion of the AV node the bundle branches, ie, the branching portions of the AV node the terminal Purkinje fibers and finally the ventricular myocardium. After the wave of excitation depolarizes these various stmetures of the heart, repolarization occurs so that each of the stmetures is ready for the next wave of excitation. Until repolarization occurs the stmetures are said to be refractory to excitation. During repolarization of the atria and ventricles, the muscles relax, allowing the chambers of the heart to fill with blood that is to be expelled with the next wave of excitation and resultant contraction. This process repeats itself 60—100 times or beats per minute... 

Fleca.inide, Elecainide acetate, a fluorobenzamide, is a derivative of procainamide, and has been reported to be efficacious in suppressing both supraventricular and ventricular arrhythmias (26—29). The dmg is generally reserved for patients with serious and life-threatening ventricular arrhythmias. Elecainide depresses phase 0 depolarization of the action potential, slows conduction throughout the heart, and significantly prolongs repolarization (30). The latter effect indicates flecainide may possess some Class III antiarrhythmic-type properties (31). 

P-Adrenoceptors have been subdivided into P - and P2-adrenoceptors. A third subset called nontypical P-adrenoceptors or P -adrenoceptors have been described but are stiU the subject of debate. In terms of the interactions with various subsets of P-adrenoceptors, some antagonists are nonselective in that they antagonize the effects of activation of both P - and P2-adrenoceptors, whereas others are selective for either P - or P2-adrenoceptors. P - and P2-adrenoceptors coexist in almost all organs but generally, one type predominates. The focus herein is on the clinically relevant P -adrenoceptor-mediated effects on heart and on P2-adrenoceptor-mediated effects on smooth muscles of blood vessels and bronchioles, the insulin-secreting tissue of the pancreas, and skeletal muscle glycogenolysis for side effects profile (36). 

Heart and Stroke Facts, American Heart Association, 1990, p. 2. 

In the past, chloroform was used extensively as a surgical anesthetic, but this use was abandoned because exposure to narcotic concentrations often resulted in sudden death from effects on the heart and circulation or from severe injury to the Hver. In addition, chloroform for this and other consumer uses was harmed by FDA in 1976 with the discovery that it is carcinogenic in mice (38). When splashed into the eye, chloroform causes local pain and irritation, but serious injury is not expected. Skin contact for single, brief exposures ordinarily causes Htde or no local irritation. 

This makes choline an important nutritional substance. It is also of great physiological interest because one of its esters, acetylcholine [51-84-3] appears to be responsible for the mediation of parasympathetic nerve impulses and has been postulated to be essential to the transmission of all nerve impulses. Acetylcholine and other more stable compounds that simulate its action are pharmacologically important because of their powerful effect on the heart and on smooth muscle. Choline is used clinically in Hver disorders and as a constituent in animal feeds. 

Capital estimates are the heart and soul of all project Justification and feasibility studies. Inaccuracies can cause serious harm to a company as well as to the engineer making the mistake. With the flow of a project from its inception to construction, many cost estimates are made. Each new estimate is based on more data, and should be more accurate. 

Theoretical work or compressor head is the heart and substance of compressor design. Some basic form of understanding must be devel oped even if involvement with compressors is less than that of design of the machine itself. Proper applications cannot be made if this understanding is absent. The following theoretical evaluations will be abbreviated as much as possible to reduce the length and still present the philosophy. For the reader with the ambition and desire, the presentation will be an outline to which the reader can fill in the spaces. 

Several chemical compounds can have an adverse effect on the heart and the vascular system. The effect may first appear as a transient change in the cardiac function. However, prolonged exposure increases the risk of permanent effects. Occasionally, functional effects such as cardiac arrhythmias may even lead to death. Furthermore, in many cases the effects of chemicals... 

Mechanisms of Cardiotoxicity Chemical compounds often affect the cardiac conducting system and thereby change cardiac rhythm and force of contraction. These effects are seen as alterations in the heart rate, conduction velocity of impulses within the heart, and contractivity. For example, alterations of pH and changes in ionic balance affect these cardiac functions. In principle, cardiac toxicity can be expressed in three different ways (1) pharmacological actions become amplified in an nonphysiological way (2) reactive metabolites of chemical compounds react covalently with vital macromolecules... 

Pellotine is a convulsant in the frog and cat. Clerc, Janot and Paris, state that the intravenous lethal dose in dogs is 10 mgm./kilo. In chloralosed dogs 5 mgm./kilo slowed the heart and caused a fall in blood pressure the effects lasted for a few minutes and resembled those due to acetylcholine they were inhibited by atropine and increased by yohimbine and ergotamine. A few injections of this dose at short intervals produced convulsions and this effect was inhibited by phenobarbitone. 

Thus far we have discussed whether a chemical reaction will occur spontaneously or only with the addition of energy. We have said nothing about the rate of chemical reactions—how fast they occur. If we need to release the energy stored in our food to power the pumping of our heart and allow us to move, we need to release that energy rapidly. We cannot afford to wait hours nr days for the energy-releasing reactions to occur. 

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