Traumatic shock. IX. Pressor therapy: The effect of paredrine on the circulation in hemorrhagic shock in dogs

The data here reported (Table I) show that a toxin is present in the blood of animals with two types of irreversible hypovolemic shock. These data also show that although blood volume therapy does not correct the hypovolemia because of continuing loss of plasma at the site of injury, the major factor in the progressive decline and death is the endotoxemia rather than the hypovolemia. This is also true of severe and prolonged hemorrhagic shock that is irreversible to transfusion. The data also show that even when there is bacterial activity at the site of injury, the pool of endotoxin in the intestine is the chief source of the circulating endotoxin. In all three types of shock, the endotoxemia develops because persisting hypovolemic shock renders the RE system unable to destroy the endotoxin. The demonstration of an endotoxemia as the cause of irreversibility and death in three types of traumatic shock caused by three different agents suggests that a single pathophysiological mechanism accounts for the phenomenon of irreversibility in all types of traumatic shock.

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TRAUMATIC SHOCK. XI. INTESTINAL ABSORPTION IN HEMORRHAGIC SHOCK 1

Journal of Clinical Investigation ◽

10.1172/jci101622 ◽

1945 ◽

Vol 24 (4) ◽

pp. 445-450 ◽

Cited By ~ 15

Author(s):

Martha Goldberg ◽

Jacob Fine

Keyword(s):

Hemorrhagic Shock ◽

Intestinal Absorption ◽

Traumatic Shock

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HDFx and Methylated DNA; With Histones Upregulated in Macrophages/ Monocytes Derived From Animal Survivors Subjected to Traumatic, Endotoxin, and Hemorrhagic Shock: Importance of Epigenesis and Potential Reasons for Resistance to Bacterial, Fungal and Viral Infections

Journal of Clinical & Experimental Immunology ◽

10.33140/jcei.05.04.07 ◽

2020 ◽

Vol 5 (4) ◽

Keyword(s):

Hemorrhagic Shock ◽

Host Defense ◽

Viral Infections ◽

White Blood Cells ◽

Nobel Laureate ◽

Traumatic Shock ◽

The Body ◽

Fluid Replacement ◽

Natural Resistance ◽

Large Numbers

Each year approximately 60,000 people die from hemorrhagic shock in the U.S.A. with about two million deaths worldwide [1]. Deaths from traumatic shock, worldwide, has been difficult to estimate, due to battles/wars in many countries, but is thought to be more than two million victims/year [1]. Many reasons for these large numbers of deaths are known [for review, see1], for example, inadequate therapeutic measures, unavailability of adequate blood/ plasma/fluid replacement, seeing the patient too late, and unavailability of trained ER personnel, among the major reasons [for recent review, see1]. Another predominant reason for large numbers of hemorrhagic and traumatic shock deaths is the risk of sepsis in many of these victims, resulting in septic shock having mortalities in excess of 40- 75%, depending upon locality, with the lower numbers in the U.S.A. Lastly, and most important is “natural resistance of the body to infectious microorganisms” (i.e, bacteria, funguses, viruses, parasitic organisms, etc.). What is responsible for “natural resistance” has been studied for more than 150 years. We know that the “innate” and “adaptive” immune systems are key elements in defense against infectious microorganisms [2, 3]. But, which elements of these systems make-up major aspects of “resistance” and “host defense” still remains to be worked out. Using starfish, more than 140 years ago, the pioneer/father of immunology, and Nobel Laureate, Elie Metchnikoff, believed that white blood cells and macrophages were key to host-defense [4]. He also believed the body develops molecules/substances, which are key to resistance to infectious microorganisms [4].

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Essential Role of P-Selectin in the Initiation of the Inflammatory Response Induced by Hemorrhage and Reinfusion

Journal of Experimental Medicine ◽

10.1084/jem.189.6.931 ◽

1999 ◽

Vol 189 (6) ◽

pp. 931-938 ◽

Cited By ~ 57

Author(s):

Rosario Scalia ◽

Valerie E. Armstead ◽

Alexander G. Minchenko ◽

Allan M. Lefer

Keyword(s):

Inflammatory Response ◽

Hemorrhagic Shock ◽

Vascular Endothelium ◽

Essential Role ◽

Ischemia Reperfusion ◽

Traumatic Shock ◽

Wild Type ◽

Neutrophil Accumulation ◽

Microvascular Endothelium ◽

Adhesive Interactions

Resuscitation from hemorrhage induces profound pathophysiologic alterations and activates inflammatory cascades able to initiate neutrophil accumulation in a variety of tissues. This process is accompanied by acute organ damage (e.g., lungs and liver). We have previously demonstrated that significant leukocyte–endothelium interactions occur very early in other forms of ischemia/reperfusion (i.e., splanchnic ischemia/reperfusion and traumatic shock) which are largely mediated by increased expression of the adhesion molecule, P-selectin, on the vascular endothelium. Here we postulated that increased endothelial expression of P-selectin in the microvasculature would play an essential role in initiating the inflammatory signaling of hemorrhagic shock. Using intravital microscopy, we found that hemorrhagic shock significantly increased the number of rolling and adherent leukocytes in the mouse splanchnic microcirculation. In contrast, mice genetically deficient in P-selectin, or wild-type mice given either an anti–P-selectin monoclonal antibody or a recombinant soluble P-selectin glycoprotein ligand (PSGL)-1 immunoglobulin, exhibited markedly attenuated leukocyte–endothelium interaction after hemorrhagic shock. Thus, activation of P-selectin protein on the microvascular endothelium is essential for the initial upregulation of the inflammatory response occurring in hemorrhagic shock. Moreover, endogenous levels of PSGL-1 mRNA were significantly increased in the lung, liver, and small intestine of wild-type mice subjected to hemorrhagic shock. Since PSGL-1 promotes adhesive interactions largely through P-selectin expressed on the vascular endothelium, this result further supports the crucial role played by P-selectin in the recruitment of leukocytes during hemorrhagic shock.

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THE RELATIONSHIP BETWEEN THE VASCULAR MANIFESTATIONS OF SHOCK PRODUCED BY ENDOTOXIN, TRAUMA, AND HEMORRHAGE

Journal of Experimental Medicine ◽

10.1084/jem.106.3.385 ◽

1957 ◽

Vol 106 (3) ◽

pp. 385-401 ◽

Cited By ~ 64

Author(s):

Benjamin W. Zweifach ◽

Lewis Thomas ◽

Keyword(s):

Hemorrhagic Shock ◽

Significant Degree ◽

Traumatic Shock ◽

Bacterial Endotoxin ◽

Vascular Effects ◽

E Coli ◽

Initial Stage ◽

Repeated Doses ◽

The Relationship ◽

Lethal Doses

The vascular effects of lethal doses of E. coli endotoxin, as observed in the mesentery of the rat, resemble the reactions of traumatic and hemorrhagic shock in the following respects: a profound inhibition of arteriolar and precapillary reactivity to topical epinephrine occurs after an initial stage of hyperreactivity; the small veins show failure to relax completely following constrictor doses of epinephrine; and the terminal vessels develop an unusual sensitivity to fluctuations in temperature of the fluid irrigating the tissue. Rats in which tolerance to bacterial endotoxin is induced, by repeated doses given daily, become highly resistant to the lethal effects of both drum trauma and hemorrhagic shock. However, rats in which the adaptation to traumatic shock is produced by repeated exposure to drum trauma, do not develop a significant degree of tolerance to lethal doses of endotoxin. The injection of small non-lethal doses of bacterial endotoxin during non-lethal episodes of trauma or hemorrhage, leads to the development of irreversible shock and death. The bearing of these findings on the problem of the relationship between endotoxin and traumatic shock is discussed.

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