Experiments Aimed at Separating the Mechanical Circulatory Effects of Ethanol From Specific Chemical Effects

Abstract

Following habitual drinking in human beings and animals, visible morphologic damage to many parts of the nervous system, including peripheral nerves, also to the heart, the liver, striated muscles, and the testes has been reported.l-16 Some of the damages are detectable by electron microscopy,0 some by optical microscopy, and some, such as congestion of vessels and edema16 and cerebral and cerebellar atrophy,2 are even grossly obvious. The ingestion of alcohol in human beings has been shown to initiate intravascular aggregation or agglutination of the circulating red cells (sludged blood) in the drinker.17In one study in 3 0 human adults ( 13 females, 17 males), microscopic observations were made of blood flow and the conditions of the small vessels in the conjunctiva, and at the same time a blood sample was taken for determination of blood ethyl alcohol concentration. Ethanol concentrations ranged from zero to 328 mg/100 ml. With increasing concentrations of alcohol in the blood, the size of aggregated or agglutinated blood cell masses increased, and the forward rates of flow in small vessels decreased correspondingly. With the higher concentrations of blood alcohol and the more severe reduction in forward flow rates, the numbers of vessels in stasis, plugged, occluded, and with no flow increased significantly. Plugged small vessels often ruptured. Within the extreme upper concentration of ethanol ( 2 2 5 and 328 mg/100 ml blood), some small vessels were ruptured, producing microscopic hemorrhages into the contiguous bulbar conjunctival tissue."In maximal good health, the blood of human beings as well as animals is completely unaggl~tinated.l*-~~ In a series of controlled experiments in animals, intravascular blood cell agglutination, in the absence of ethanol, has been shown to initiate histopathologically recognizable lesions in the nervous system, kidney, liver, and heart. Further, it has been shown that intravascular agglutination in the absence of alcohol, if sufficiently severe, can reduce the forward rates of flow of the blood in the brain, decrease the concentration of oxygen available to nervous tissue, increase the permeability of the blood-brain barrier, and cause sufficient damage to nervous tissue to initiate deficits ranging from weakness and clumsiness to varying degrees of temporary or protracted paralysis or convulsions, to periods of unconsciousness, sometimes decerebrate rigidity, and even death. These experiments have been reviewed in detai1.21a22 See also confirmatory evidences by Stalker24 and by Bicher and colleague^.^^ Ingested ethanol, by initiating agglutination of the blood cells and thereby forcibly reducing the rates of flow of blood through capillaries, directly causes enormous numbers of small volumes of tissue in different parts of many tissues * These investigations were aided by United States Public Health Service Grants HE-04176, HE-07114, and HTS-5340. 356

The Pharmacology of Sedative/Hypnotics, Alcohol, and Anesthetics: Sites and Mechanisms of Action

“…The possibility has not been ruled out that ethanol's actions are, in part at least, associated with a reduction of microcirculation (MOSKOW et al, 1968;KNISELY et al, 1969;PENNINGTON and KNISELY, 1973). Data exist to support a direct relationship; there have been no confirming studies of which this writer is aware.…”