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HANDBOOK OF PHYSIOLOGY 



CIRCULATION I 



similar to that described for high calcium (see 

 section iv). 



Although many opinions have been expressed on 

 the question whether cardiac muscle contractility is 

 depressed by magnesium ion, there is little evidence 

 from which to draw a conclusion. For example, 

 Smith ('/ al. {279) assert that normal systole is main- 

 tained until cardiac arrest supervenes in their experi- 

 ments, but this is based on the fact that the heart 

 on observation showed a "well-defined and vigorous 

 systole." The heart-lung preparation described by 

 Stanbury & Farah (286) performs a given stroke 

 work at a higher than normal filling pressure in 14 

 meq per liter of magnesium, and filling pressure 

 drops on addition of calcium. Such impairment of 

 function as this may represent could be caused by 

 intraventricular conduction blocks (279) rather than 

 a direct effect on the muscle. Garb finds that the 

 isometric tension developed by cat papillary muscle 

 is not influenced by magnesium concentrations over 

 a range from o to 10 times normal (83). On the 

 other hand, an increase of magnesium concentration 

 by 6 mM per liter in the solution bathing an isolated 

 frog heart caused an immediate drop in developed 

 tension, which could be brought back to normal by 

 increasing the duration of the square pulse used to 

 stimulate the muscle (unpublished observations). 

 Further studies are needed to establish at what steps 

 in the excitation-contraction process magnesium 

 exerts an effect. 



In relationship to the last question certain comple- 

 mentary facts come to mind, a) Magnesium blocks 

 neuromuscular transmission, and the effect can be 

 counteracted by calcium, b) Neither magnesium nor 

 calcium affect the contractile response of skeletal 

 muscle to direct electrical stimulation, c) In contrast, 

 the contractile response of cardiac muscle is very 

 sensitive to changes in calcium, and perhaps reacts in 

 the opposite fashion to magnesium, d) Magnesium 

 appears to enter cardiac muscle more readily than 

 skeletal muscle. The resistance of most cells to accu- 

 mulation of magnesium had been noted previously 

 (280). In recent experiments it has Ijeen found that 

 injection of Mg-' intravenously is followed by accumu- 

 lation of radioactivity in heart muscle to an extent 

 10 times greater than that in skeletal muscle. It has 

 been shown that this is not a function of stimulation 

 of the muscle, nor is it due to excessive accumulation 

 in Purkinje fibers (30, 94). Skeletal muscle, then, 

 exhiijits less uptake of magnesium tracer than does 

 heart and is not directly affected by variations in 

 extracellular calcium or magnesium. Cardiac muscle 



may be more like tiie neuromuscular junction, both 

 calcium and magnesium perhaps being capable of 

 reaching superficial sites where these ions may affect 

 steps in the e.xcitation-contraction process. 



Magnesium deficiency is encountered clinically 

 in man, usually because of a generally poor nutritional 

 status secondary to chronic alcoholism or gastro- 

 intestinal tract dysfunction (233). Nonspecific ST 

 segment and T wave changes are often seen under 

 these conditions, and sometimes a slow change 

 back toward normal occurs during the course of 

 therapy. The improvement is not necessarily corre- 

 lated with the change in serum magnesium concen- 

 tration, however, and many other factors in the 

 clinical course may contribute to the final result. 



It was observed many years ago that the magnesium 

 concentration expressed in mg per 100 g of dry 

 tissue was abnormally low in hearts of patients dying 

 in congestive failure (327). Since phosphorus and 

 potassium were also decreased, there is a possibility 

 that the chemical findings reflect a relative decrease 

 in cell mass. Any result which pointed specifically to 

 magnesium loss would be of interest because of the 

 possible relationship of magnesium to normal muscle 

 function. [For example, magnesium inhibits calcium- 

 activated myosin ATPase (105).] 



Barium 



Barium has been known, since the time of Boehm 

 (18) in 1875, to affect electrical properties of cardiac 

 muscle. Many workers (23, 103) have shown in both 

 ainphibian and mammalian preparations that barium 

 chloride can initiate spontaneous activity in cardiac 

 muscle. Other changes may also occur. For example 

 Kleinfeld et al. (176) found that injection of barium 

 chloride into the dorsal lymph sac of the frog was 

 followed by A-V block, idioventricular rhythm, 

 ventricular extrasystoles, and ventricular tachycardia. 



The effect of barium on the cardiac action potential 

 was shown by Kleinfeld and co-workers (176) to 

 consist of a marked lengthening of the terminal 

 portion of the recovery phase of the action potential. 

 Comparable tracings were obtained by Greengard & 

 Straub (loi) from rabbit cervical sympathetic trunk 

 B and C fibers bathed in isotonic barium chloride. 

 It would appear that calcium (149), barium (loi, 

 176), and strontium (loi) may all prolong the 

 terminal phase of repolarization of the action poten- 

 tial. This is in contrast to the effects of a) calcium 

 and magnesium-free solutions, or h) high strontium 

 in the presence of low calcium, which arc Ijoth 



