Does an ip E.coli injection (10^8 ) cause death in 4 hours in C57BL/6? Do I need to hydrate the mouse? Is this a good concentration to mimic a septic situation?
The answer is yes, in theory, provided the injectate contained an adequate “loading dose” of the E. Coli bacteria.
The lung is a “target organ” for stress, because it is rich in vascular endothelium (VE), tissue factor (TF), and autonomic innervation. The direct exposure of the toxic E Coli injectate to lung tissue would induce a violent inflammatory reaction in the lung that would be analogous to the lethal inflammatory lung reaction that killed healthy young people within 24 hours of exposure to the hyper-virulent influenza virus during the 1918 influenza epidemic that killed more people than the bombs and bullets of WWI. The more recent COVID contagion, and especially its deadly mRNA injections, caused a similar deadly reaction that killed healthy young people without warning symptoms. The toxic bacterial injectate would precipitate a lethal inflammatory reaction in the delicate alveolar tissue, which consists of a layer of specialized pneumocytes and a layer of specialized VE cells.
The extravascular pneumocytes produce TF, a hormone that is normally isolated from blood enzymes by the vascular endothelium. When TF enters flowing blood, it binds to, stabilizes, and activates hepatic coagulation factor VII, which “triggers” the enzymatic interaction of factors VII, VIII, IX and X that generates thrombin, and converts fibrinogen to soluble fibrin and insoluble fibrin.
Thrombin energizes all the enzyme and cell activities of the mammalian stress mechanism that repairs tissues and regulates organs, including inflammation that dissolves the basement membrane to loosen tight cell connections and facilitate chemotaxis of repair cells. Thrombin also energizes tiny muscle fibers within the cells of the VE to cause “gap formation” between the cells of the VE that allows factor VII to “penetrate” into extravascular tissues and also allows TF to “escape” into flowing blood.
The intravascular, selectively permeable VE isolates TF from blood enzymes. It also manufactures von Willebrand Factor (VWF) and releases it into flowing blood in accord with nervous activity.
VWF binds to, stabilizes, and activates hepatic enzyme factor VIIIC to form a gigantic molecular complex called “factor VIII.” Factor VIII interacts with factors VII, IX and X to produce factor XIII, which converts soluble fibrin into insoluble fibrin that polymerizes into protein strands that entangle blood cells to increase blood coagulability, exaggerate capillary flow resistance, and bind blood cells together to form a viscoelastic clot when blood coagulability rises above a critical threshold.
The sudden exaggeration of systemic blood coagulability would precipitate abnormal systemic blood clot formation beginning in small peripheral arteries throughout the body which suddenly increases flow resistance and disrupts the mechanism of oxygen transport and delivery, causing sudden, painless death. Read my attached essays. www.stressmechanism.com