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doi: 10.1084/jem.8.2.252pmid: 19867038
Since the hæmolysins of the several venoms respond differently to photodynamic action, they may be regarded as possessing different chemical constitutions. As regards stability, cobra hæmolysin ranks first, daboia second, and Crotalus third. The toxicity of all the venoms is more or less diminished by eosin and erythrosin in sunlight. This reduction in toxicity depends upon chemical changes, of more or less profound nature, taking place in certain of the active principles of the venom. The more stabile the predominant active principles the less the reduction in toxicity, and vice versa. Venom-neurotoxins are highly resistant to photodynamic action, venom-hæmolysins are less resistant, while the hæmorrhagin and thrombokinase of Crotalus and daboia venoms exhibit weak powers of resistance to their action. Hence it follows that while cobra venom remained almost unaltered, rattlesnake and daboia venoms were greatly reduced in toxicity when mixed with the fluorescent dyes and exposed to sunlight. There is an interesting parallel between the action of eosin and erythrosin upon the different venoms and their reactions to other injurious agencies. For example, the hæmolysins of cobra and daboia venoms are more heat resistant than the hæmolysin of Crotalus venom, and the former are less injured by the dyes than the latter. The neurotoxin of the former venoms is also more heat stabile than that of the rattlesnake, and the same relative degree of resistance holds for this substance and the anilines. Just as the hæmorrhagin of rattlesnake venom and the thrombokinase of daboia venom are destroyed by a temperature of 75° C., so are they readily inactivated by the photo dynamic substances employed. The globulin-precipitating and blood corpuscle-protecting principle of cobra venom is relatively thermostabile and in contradistinction to the immunity-precipitins it is also unaffected by eosin and erythrosin. This study of the action of photodynamic substances upon snake venoms serves again to bring out the fact of their highly complex nature, and while enlarging somewhat the field in which photodynamic activity is known to operate, it also proves that this form of destructive activity is affected by the same conditions of resistance as confront the action of the usual physical and chemical agents.
Stewart, G. N.; Guthrie, C. C.; Burns, R. L.; Pike, F. H.
doi: 10.1084/jem.8.2.289pmid: 19867041
The cerebral circulation was interrupted for periods of three to eighty-one minutes by ligation of the innominate and left subclavian arteries proximal to the origin of the vertebral, in ninety-three cats. Eleven dogs were used in the earlier experiments. The eye reflexes disappear very quickly and a period of high blood pressure follows the occlusion immediately; vagus inhibition causes cardiac slowing and a fall in blood pressure, followed by a second rise after the vagus center succumbs to anaemia. Respiration stops temporarily (twenty to sixty seconds) after the beginning of occlusion, and then follows a series of strong gasps of the Cheyne-Stokes type, after which it stops until some time after the restoration of the cerebral circulation. The respiratory and vagus centers lose their power of functioning at approximately the same time. Asphyxial slowing of the heart may occur without the agency of the vagus center. The blood pressure slowly falls to a level which is maintained throughout the remainder of the period of occlusion. The anterior part of the cord and the encephalon lose all function; no reflexes are obtainable. The reflexes of the posterior part of the cord persist; the intravenous injection of strychnine does not affect the anterior part of the cord during the period of occlusion; but does affect the posterior portion of the cord. There is no secretion of tears or saliva, and the intra-ocular pressure is reduced. The blood pressure falls still more after release of the cerebra arteries, but soon begins to rise. The respiration returns suddenly, two to sixty minutes after restoration of the cerebral circulation, the first gasp being a strong one. The rate gradually increases until rapid enough for natural respiration. The eye reflexes and intra-ocular tension return more gradually, ten minutes to three hours after restoration of the cerebral circulation. The anterior part of the cord recovers its functions gradually. The first reflexes occur only on the same side as the stimulus, crossing of reflexes, to involve the other side, not occurring till later. As a rule, all reflexes return, and a short period of quiet follows. The anterior part of the cord again becomes irritable to strychnine, but succumbs to its action before the normal part. Spasms, of tonic, clonic, or mixed type, then appear, terminating in (a) death, (b) partial or (c) complete recovery. In partial recovery, disturbances of locomotion, such as walking in a circle, paralysis, dementia, loss of sight, hearing, and general intelligence, characterize the post-convulsive period. After complete recovery, there is a return to normal deportment. No gross lesions of the nervous system, other than a congested appearance of the previously anæmic area, were observed. Transection of the spinal cord stops the spasms below the level of section. Hemisection of the cord stops the spasms on the same side, below the level of section. Death, without any return of the reflexes after release of the cerebral arteries, has followed an occlusion of seven and one-half minutes. Respiration has returned after an occlusion of one hour. Five animals have recovered completely after an occlusion of seven minutes or more. Only one animal has recovered completely after an occlusion of fifteen minutes. No animal has recovered completely after an occlusion of twenty minutes. In Herzen's 26 resuscitation of an animal after several hours of cerebral anæmia, there must have been some anastomotic channels to the brain. Mayer's 27 limit of ten to fifteen minutes of cerebral anæmia, beyond which resuscitation is not practicable, is close to the correct one. It appears to us that, in cases of resuscitation two hours after cessation of the heart-beat, (Prus., loc.cit.) the auricles must have kept up a slow but, in some degree, an efficient movement of the blood through the brain. The truth of this suggestion might be tested by introducing some easily recognized, non-diffusible substance into a vein after the heart-beat ceases to affect a manometer, and later searching for it in the brain and other parts of the body. But, whatever the reason, cerebral anaemia in these cases must have been less complete than in our experiments. The histological alterations of the cord and brain are now being studied. The results will be published later.
doi: 10.1084/jem.8.2.322pmid: 19867042
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