THE FUNCTIONAL EFFECT OF EXPERIMENTAL INTRASPINAL INJECTIONS OF SERA WITH AND WITHOUT PRESERVATIVES.

The monkey (Macacus rhesus) usually tolerates readily the repeated intraspinal injection of large doses of 0.3 per cent. tricresol antimeningitis serum. The spontaneous respiration is generally not disturbed. Doses of 0.3 per cent. tricresol serum as large as 8 c.c. per kilo were injected intraspinally with subsequent recovery, even when the monkey had a partial pneumothorax. Dangerous alterations of the respiration and blood pressure in the monkey after 0.3 per cent. tricresol serum given by syringe are apparently largely due to increased intraspinal pressure, for the mere reduction of this pressure has sufficed to bring about a prompt and complete recovery. The medullary centers of the monkey (vagus, respiratory, and vasomotor) are highly resistant to the action of sera when injected intraspinally, strikingly more so than those of the dog. Occasionally the mere introduction of a hypodermic needle into the spinal dural sac of non-anesthetized, unoperated monkeys which have already received injections of 0.3 per cent. tricresol serum, may produce a severe collapse. A preceding partial asphyxia seems to be a necessary condition. Large quantities of sera are rapidly absorbed from the spinal dural sac of monkeys, and the clotting time of the blood is decreased. The spinal meninges of the monkey are resistant to infection; even primitive precautions during intraspinal injections apparently suffice to prevent infection. Dogs are much more sensitive to the intraspinal injection of 0.3 per cent. tricresol serum than monkeys; nevertheless they may tolerate as much as 6 c.c. per kilo provided that intratracheal insufflation is maintained for some time after each injection. The chief danger in dogs after intraspinal injections of 0.3 per cent. tricresol is a cessation of the respiration; for this reason artificial respiration is necessary. The blood pressure in the dog may be profoundly lowered by 0.3 per cent. tricresol serum, yet recovery is usually obtained if intratracheal insufflation is maintained. The effects of 0.3 per cent. tricresol serum upon the medullary centers is interpreted to be the result of either excitatory or inhibitory stimuli. No evidence was found that either the respiratory, vasomotor, or vagus center is paralyzed. The local application of 0.3 per cent. tricresol serum upon the exposed medulla of dogs does not produce the same effect upon the respiration and blood pressure as intraspinal injection of the same serum. A solution of 0.3 per cent. tricresol serum applied locally to the medulla of dogs occasionally produces a transient respiratory stop page, without markedly affecting the blood pressure even when intratracheal insufflation is stopped. Increased intraspinal pressure was found to be an important factor in the production of respiratory and blood pressure changes in the dog after intraspinal injection of 0.3 per cent. tricresol serum. Both in the monkey and in the dog 0.3 per cent. chloroform serum, 0.3 per cent. ether serum, or plain horse serum produced in general a smaller effect upon the medullary centers than 0.3 per cent. tricresol serum. The ideal preservative for therapeutic sera would seem to be one which could be removed before injection. Ether in this respect is better than chloroform. The opsonins in antimeningitis serum are about equally affected by 0.3 per cent. tricresol, 0.3 per cent. chloroform, or 0.3 per cent. ether when tested after one week, one month, and three months. When intraspinal injections are given in the human being it would seem advisable to be prepared to withdraw part of the injected fluid and to administer artificial respiration, if necessary. For a safe withdrawal of fluid the gravity method is the best; for artificial respiration Meltzer's apparatus for pharyngeal insufflation is recommended.