Silvio Baez

Hepatorenal Factors in Circulatory Homeostasis IV. Tissue Origins of the Vasotropic Principles, VEM and VDM, Which Appear during Evolution of Hemorrhagic and Tourniquet Shock

Studies were carried out in dogs and rabbits subjected to hemorrhagic and tourniquet shock to determine the tissue origins of two newly described vasotropic principles, VEM and VDM. The vasoexcitor principle, VEM, predominates in the blood during the initial compensatory stage and was traced to the kidney. The vasodepressor principle, VDM, prevails during the decompensatory phase and was found to originate in the liver, skeletal muscle and spleen. During the decompensatory phase, there was a progressive deterioration of the hepatic mechanisms for inactivating VDM. Sequential tissue hypoxia during shock is probably responsible for the formation of these vasotropic principles and for the deterioration of the hepatic VDM inactivation system. Special emphasis is placed on the effects of local concentrations of VDM within the liver and on the resultant diversion of blood from the general circulation into the splanchnic viscera.

Dibenzyline protection against shock and preservation of hepatic ferritin systems.

Pretreatment with Dibenzyline, an adrenergic blocking agent, markedly increased the survival rate of normal, arenal or adrenalectomized rats subjected to drum trauma, and of normal rats subjected to prolonged hemorrhagic hypotension. In the latter a larger residual circulating blood volume was not responsible for the increased survival since average maximal blood loss was equal in treated and control rats. Congestion of the liver and gut, regularly seen in the controls, was notably absent in the Dibenzyline-protected rats. Direct microscopic observation of the terminal vascular bed in the mesoappendix, throughout the hemorrhagic procedure, revealed earlier appearance of decompensatory changes and increased vascular fragility in the controls. In livers removed at the end of the hemorrhagic and traumatic procedures, ferritin systems were preserved in treated rats, in contrast to their deterioration in controls. It is suggested that the protection conferred by pretreatment with Dibenzyline may not be due solely to its adrenergic blocking properties, but in part to a direct cellular action in the liver, exemplified by its in vitro protection of the ferritin systems against hypoxic damage.

Hepato-Renal Factors in Circulatory Homeostasis. II. Disappearance of Hepatic Vaso-Depressor Material Following Intravenous Administration

Summary In vitro studies have shown that the vasodepressor principle, which appears during the hypo-reactive stage of shock and results from the anoxia of liver and skeletal muscles, can be inactivated under aerobic conditions by healthy liver slices. The present study was concerned with the mechanisms by which endogenous and exogenous VDM are removed from the circulation of the living animal. The exogenous VDM was concentrated and purified from saline extracts of anaerobic beef liver. The endogenous VDM was released into the blood following liver anoxia produced by temporary occlusion of the hepatic artery in a partially eviscerated preparation. Two mechanisms for VDM removal were revealed: (1) its inactivation by the healthy liver; (2) its excretion into the urine by the normal kidney. A preliminary period of hepatic anoxia rendered the liver incapable of inactivating VDM in vivo, presumably through anoxic damage to the hepatic enzyme system for this function. This situation is analogous to the progressive impairment of the VDM inactivating mechanism in the liver which develops during the course of shock and which is considered responsible for the perpetuation of the hypo-reactive state of the peripheral vascular system. The loss of the renal excretory function for VDM during hypo-reactive shock deprives the animal of an important means of clearing the blood of VDM and thereby aiding in liberating the vascular bed from this decompensatory vasotropic principle.

Influence on Hepatic Ferritin Systems of Tertiary Amine, G-D 131, with Beneficial Effects in Shock.

Summary These observations with G-D 131 are regarded as support for our concept that deterioration of the hepatic ferritin mechanisms brings about consequences of major importance for ability of the animal to survive a standardized shock procedure.

Cellular sites of hepatic ferritin activation and inactivation.

Studies with viable reticulo-endothelial (RE) and parenchymal cells separated from the liver show that the parenchymal cells contain most of the liver ferritin. This ferritin is vasoinert, and anae...