| Time | Salts other than NaCl injected | m/6 NaCl injected in c.c. | Urine in c.c. |
|---|---|---|---|
| 9:25 | |||
| 11:40 | 150 | 64.5 | |
| 11:45 | 10 | 6.6 | |
| 11:50 | 10 | 5.6 | |
| 11:55 | 10 | 6.2 | |
| 12:00 | 10 | 7.4 | |
| 12:05 | 10 | 9.5 | |
| 12:05 | 5 c.c. m/6 CaCl2 | ||
| 12:10 | 5 | 2.2 | |
| 12:15 | 10 | 0.8 | |
| 12:20 | 10 | 1.2 | |
| 12:25 | 10 | 1.6 | |
| 12:30 | 10 | 2.8 | |
| 12:35 | 8 | 3.0 | |
| 12:40 | 5 | 4.5 | |
| 12:45 | 0 | 4.8 | |
| 12:50 | 0 | 5.1 | |
| 12:55 | 0 | 6.2 |
It was found in another series of experiments[58] that the haemoglobinuria caused by saponin and by quillain, which is a dried extract of Quillaja bark, may be inhibited by calcium chloride. The intravenous injection of 2 c.c. ¹⁄₄% quillain always produced haemoglobinuria in a rabbit weighing about 1,200 g. If the dilution of the quillain were made with m/6 CaCl2 instead of water, e.g., 2 c.c. 1% quillain + 6 c.c. m/6 CaCl2 and 2 c.c. of this injected intravenously, no haemoglobinuria resulted, although the concentration of the quillain was the same in both cases. The CaCl2 does not stop the excretion of the haemoglobin by the kidneys, for if the saponin or quillain be given first and the haemoglobinuria established, the subsequent injection of CaCl2 does not stop the excretion of haemoglobin. This is explained by a large number of experiments in which it was shown that the haemolysis caused by saponin, quillain, or digitalin is particularly inhibited by calcium chloride and magnesium chloride. This can be seen in the following table in which defibrinated rabbit’s blood is used, and the effects of CaCl2 and MgCl2 are compared with that of NaCl.
| Time | 1 c.c. blood 5 c.c. m/6 NaCl 3 drops 0.5% saponin | 1 c.c. blood 5 c.c. m/6 MgCl2 3 drops 0.5% saponin | 1 c.c. blood 5 c.c. m/6 CaCl2 3 drops 0.5% saponin |
|---|---|---|---|
| A.M. | |||
| 10:22 | |||
| 10:24 | change of color | no change | no change |
| 10:27 | almost transparent | no change | no change |
| 10:30 | laking almost complete | no change | no change |
| 10:45 | laking complete | no change | no change |
| P.M. | |||
| 1:00 | laking complete | corpuscles settled to bottom; supernatant fluid colored; mixture quite opaque on shaking | same as MgCl2 mixture |
It is of considerable interest to note that these substances, saponin, quillain, and digitalin, act not only as haemolytics, but also as diuretics. This was shown in a number of experiments.[59] As shown in the following table, the injection of a very small quantity of saponin produces a distinct increase in the quantity of urine excreted.
| Time | m/6 NaCl injected intravenously | Urine |
|---|---|---|
| 10:15 | ||
| 10:20 | 10 c.c. | 2 c.c. |
| 10:25 | 20 c.c. | 4 c.c. |
| 10:30 | 20 c.c. | 6 c.c. |
| 10:35 | 10 c.c. | 7.5 c.c. |
| 10:40 | 10 c.c. | 8.0 c.c. |
| 10:45 | 10 c.c. | 8.2 c.c. |
| 10:50 | 10 c.c. | 7.9 c.c. |
| 10:56 | Injected 2 c.c. ¹⁄₂₀% saponin in m/6 NaCl | |
| 11:00 | 10 c.c. | 10.5 c.c. |
| 11:05 | 10 c.c. | 11.0 c.c. |
| 11:10 | 10 c.c. | 11.0 c.c. |
| 11:15 | 10 c.c. | 11.0 c.c. |
| 11:16 | Injected 1 c.c. ¹⁄₂₀% saponin | |
| 11:20 | 10 c.c. | 12.2 c.c. |
| 11:25 | 10 c.c. | 13.2 c.c. |
| 11:30 | 10 c.c. | 12.0 c.c. |
| 11:35 | 10 c.c. | 12.5 c.c. |
It is possible that it is by no means a coincidence that these substances which are powerful haemolytics act also as diuretics; and that CaCl2 and MgCl2, which inhibit the secretion of urine, also to some extent inhibit the haemolytic action. It is difficult to say by what process the haemoglobin is liberated from the red blood corpuscle, as indeed it is difficult to state definitely how fluid passes from the blood into the urine. It is sufficient to call attention to the fact that the liberation of haemoglobin and the flow of urine may be to some extent controlled by the same conditions. If the haemolytics such as saponin cause haemolysis by increasing the permeability of the membranes of the red blood corpuscles, it seems possible that the diuretic effect of these substances may be due to a similar process in the kidney. If this be true, changes in permeability must play an important part in the action of these diuretics. And it is not impossible that the inhibition of the haemolytic action of saponin, etc., as well as the inhibition of the flow of urine by CaCl2 and MgCl2, may be due to a decreased permeability of the red blood corpuscle on the one hand, and of the kidney cells on the other.
With these numerous experiments with calcium and magnesium it is still impossible to make a general statement as to the nature of their action. Since the chemical conditions existing in the tissues of animals and of various parts of animals are largely a matter of conjecture, we cannot predict how these substances will act; nor can we say that because calcium, for example, has a certain action in one animal or on one organ it will necessarily have the same action in other animals or in other organs.
In the experiments on the rabbit’s intestine, however, calcium and magnesium have been shown to have an action which can only be described as inhibitory. In an animal as highly organized as the rabbit, the intestine is an extremely complex organ; it is not only a muscular and a glandular organ, but contains a complicated nervous mechanism peculiar to itself which is entirely inseparable from the other parts. It is not possible here to mechanically isolate a part which shall be free from the nervous system as can be done almost completely in the center of the jellyfish and the apex of the heart. We are dealing with an entire organ which must be considered as an indicator by which comparative results may be obtained. So many unknown conditions exist in such an organ that it is impossible to say what tissue is acted on primarily, whether the nervous system on the one hand, or the glandular and muscular tissues on the other. There are, however, two indicators in the intestine by which the comparative actions of substances can be studied, namely, the muscular movements, and the secretion of fluid, both of which by various chemical substances may be increased or lessened; or, in other words, they may be stimulated or inhibited. These terms are entirely comparative. The fact that calcium and magnesium act as inhibitors for both the muscular and secretory activities of the intestine does not imply that they have a similar action in other organs or in all animals. It can only be said with certainty that the chemical conditions under which the intestines of the rabbit live are fairly constant, so that the addition of calcium or magnesium in some way constantly inhibits the activity of both muscular and glandular tissues, and the addition of certain purgative salts constantly stimulates them to greater activity.
FOOTNOTES:
[49] Journal of Physiology, Vols. 4, 5, 6, 8, 16, 17, and 18, 1883-1895.