The primary value of blood to the body must have been one of the earliest observations of reasoning beings. When we consider the variety of fundamental services which this circulating fluid performs—the conveyance of food and oxygen to all the tissues, the removal of waste, the delivery of the internal secretions, the protection of the body against toxins and bacterial invasion, and the distribution of heat from active to inactive regions—the view of the ancient Hebrews that the “life of the flesh is in the blood” is well justified. It is naturally of the utmost importance that this precious fluid shall be safeguarded against loss. And its property of turning to a jelly soon after escaping from its natural channels assures a closure of the opening through which the escape occurred, and thus protection of the body from further bleeding. The slight evidence that adrenin hastens the clotting process has already been hinted at. When we found that adrenin is set free in pain and intense emotion, it seemed possible that there might exist in the body an arrangement for making doubly sure the assurance against loss of blood, a process that might nicely play its rôle precisely when the greatest need for it would be likely to arise.
It was in 1903, while tracing in dogs the rise and fall of sugar in the blood after administering adrenin, that Vosburgh and Richards[1] first noted that simultaneously with the increase of blood sugar there occurred more rapid coagulation. In some cases the diminution was as much as four-fifths the coagulation time of the control. Since this result was obtained by painting “adrenalin” on the pancreas, as well as by injecting it into the abdominal cavity, they concluded that “the phenomenon appears to be due to the application of adrenalin to the pancreas.” Six years later, during a study of the effect of adrenalin on internal hemorrhage, Wiggers[2] examined incidentally the evidence presented by Vosburgh and Richards, and after many tests on five dogs found “never the slightest indication that adrenalin, either when injected or added to the blood, appreciably hastened the coagulation process.” In 1911 von den Velden[3] reported that adrenin (about 0.007 milligram per kilo of body weight) decreased the coagulation time in man about one-half—an effect appearing 11 minutes after administration by mouth, and 85 minutes after subcutaneous injection. He affirmed also, but without describing the conditions or giving figures, that adrenin decreases coagulation time in vitro. He did not attribute the coagulative effect of adrenin in patients to this direct action on the blood, however, but to vasoconstriction disturbing the normal circulation and thereby the normal equilibrium between blood and tissue. In consequence, the tissue juices with their coagulative properties enter the blood, so he assumed. In support of this theory he offered his observation that coagulation time is decreased after the nasal mucosa has been rendered anemic by adrenin pledgets. Von den Velden’s claim[3] for adrenin given by mouth was subjected to a single test on man by Dale and Laidlaw,[4] but their result was completely negative.
The importance of Vosburgh and Richards’ observation, the thoroughly discordant testimony of later investigators, as well as the meager and incidental nature of all the evidence that has been adduced either for or against the acceleration of clotting by adrenin, made desirable a further study of this matter. Especially was this further study desirable because of the discharge of adrenin into the blood in pain and emotional excitement. Accordingly, in 1914, H. Gray and I[5] undertook an investigation of the question. In doing so we employed cats as subjects. Usually they were quickly decerebrated under ether, and then continuance of the drug became unnecessary. Body temperature was maintained by means of an electric heating pad. Respiration proceeded normally except in a few instances (in which, presumably, there was hemorrhage into the medulla), when artificial respiration had to be given.
The Graphic Method of Measuring the Coagulation Time
In order to avoid, so far as possible, the personal element in determining when the blood was clotted, the blood was made to record its own clotting. The instrument by means of which this was done was the graphic coagulometer devised by W. L. Mendenhall and myself,[6] and illustrated diagrammatically in [Fig. 24]. It consists essentially of a light aluminum lever with the long arm nearly counterpoised by a weight W. The long arm is prevented from falling by a support S, and is prevented from rising by a horizontal right-angled rod reaching over the lever at R1 and fixed into the block B which turns on the axis A. Into the same block is fixed the vertical rod R2. When this rod is moved from the post P1, against which it is held by the weight of the horizontal rod R1, towards the other post P2, the check on the long arm of the lever is lifted, and if the short arm is heavier, the long arm will then rise.
Figure 24.—Diagram of the graphic coagulometer. The cannula at the right rests in a water bath not shown in this diagram. For further description see text.
The cannula C, into which the blood is received, is two centimeters in total length and slightly more than two millimeters in internal diameter. It is attached by a short piece of rubber tubing to the tapered glass tube T, five centimeters long and five millimeters in internal diameter. The upper end of this tube is surrounded by another piece of rubber which supports the tube when it is slid into the U-shaped support U, fixed directly below the end of the short arm of the lever.
By drawing the cannulas from a single piece of glass tubing and by making the distance from shoulder to upper end about twelve millimeters, receptacles of fairly uniform capacity are assured. All the dimensions, the reach of the rubber connection over the top of the cannula (2–3 millimeters), the distance of the upper rubber ring from the lower end of the glass chamber (4 centimeters), etc., were as nearly standard as possible.
A copper wire D, eight centimeters long and 0.6 millimeters in diameter, bent above into a hook and below into a small ring slightly less than two millimeters in diameter, is hung in a depression at the end of the short arm of the lever. The small ring then rests in the upper part of the cannula (see [Fig. 24]). The weight of the copper wire makes the short arm of the lever heavier than the long arm by 30 milligrams, when the delicate writing point is moving over a lightly smoked drum. Half a dozen of these standard wires are needed.