MS_HOPE wrote:Due to my MS-fogged brain, I can't say that I'm following much of the technical discussion here. But I'm VERY much appreciating the respectful, civil tone, and the spirit of explaining and educating. Thank you, guys (and gals?).
Malden wrote:MS_HOPE wrote:Due to my MS-fogged brain, I can't say that I'm following much of the technical discussion here. But I'm VERY much appreciating the respectful, civil tone, and the spirit of explaining and educating. Thank you, guys (and gals?).
You are not alone in this fogg... this is just ours "lucida intervala"
Cece wrote:What I notice about Malden's diagram is that the arrows all go one way. But in CCSVI, there is reflux. There should be arrows on the diagram also going the other way. The blood volume within the stenosed area will not equal the total blood volume in the area just before the stenosed area. This will affect the equations.
Cerebral Ischemia-Hypoxia Induces Intravascular Coagulation and Autophagy.
F Adhami, G Liao, YM Morozov, A Schloemer, VJ Schmithorst, JN Lorenz, RS Dunn, CV Vorhees, M Wills-Karp, JL Degen, RJ Davis, N Mizushima, P Rakic, BJ Dardzinski, SK Holland, FR Sharp, CY Kuan
Hypoxia is a critical factor for cell death or survival in ischemic stroke, but the pathological consequences of combined ischemia-hypoxia are not fully understood. Here we examine this issue using a modified Levine/Vannucci procedure in adult mice that consists of unilateral common carotid artery occlusion and hypoxia with tightly regulated body temperature. At the cellular level, ischemia-hypoxia produced proinflammatory cytokines and simultaneously activated both prosurvival (eg, synthesis of heat shock 70 protein, phosphorylation of ERK and AKT) and proapoptosis signaling pathways (eg, release of cytochrome c and AIF from mitochondria, cleavage of caspase-9 and -8). However, caspase-3 was not activated, and very few cells completed the apoptosis process. Instead, many damaged neurons showed features of autophagic/lysosomal cell death. At the tissue level, ischemia-hypoxia caused persistent cerebral perfusion deficits even after release of the carotid artery occlusion. These changes were associated with both platelet deposition and fibrin accumulation within the cerebral circulation and would be expected to contribute to infarction. Complementary studies in fibrinogen-deficient mice revealed that the absence of fibrin and/or secondary fibrin-mediated inflammatory processes significantly attenuated brain damage. Together, these results suggest that ischemia-hypoxia is a powerful stimulus for spontaneous coagulation leading to reperfusion deficits and autophagic/lysosomal cell death in brain.
One of the most surprising findings of the present study is that the decline of CBF in conjunction with hypoxia is sufficient to induce rapid microvascular thrombosis and fibrin deposition within the brain (Figure 9) . By analyzing challenged fibrinogen-null mice we have established that fibrin(ogen) plays an important role the reperfusion deficits and brain infarction (Figure 10) . These results suggest that if cerebral ischemia is accompanied with hypoxia, this combination can precipitate local coagulation and impede reperfusion after ischemia, similar to the previously described no-reflow phenomenon after cerebral ischemia5 and cardiac arrest.56 It seems likely that fibrin stabilization of platelet thrombi is a major determinant of brain tissue damage. If so, we would predict that a similar, if not more impressive, protection from tissue damage could be realized in mice with a profound defect in platelet function. It is also conceivable that fibrin-mediated inflammatory processes drive secondary tissue damage in the brain. Thus, the modified Levine/Vannucci model described here may be useful for testing new therapies to restore postischemic reperfusion in the face of thrombolytic agents and other approaches to reopened large vessels.
Regarding the mechanism of ischemia/hypoxia-induced thrombosis, it seems likely that hypoxia alters the balance between anti- and procoagulation properties of the endothelial cells in cerebral blood vessels. Although focal ischemia can trigger platelet accumulation and fibrin deposition, these events typically show a late-onset after a transient hyperemia phase.49,53 In contrast, the present study shows that the combination of ischemia and hypoxia precipitates these events almost immediately. Understanding the mechanism by which combined ischemia-hypoxia alters the homeostatic properties of endothelial cells in cerebral vessels may suggest novel prophylactic therapies in clinical situations when the imminent risk of cerebral ischemia and hypoxia is high, such as coronary bypass surgery.
Malden wrote:Reflux is past time, even Zamboni avoid to mention it in his last statement about CCSVI.
Contradictory reports on the significance of several hemodynamic phenomena, such as femoral vein incompetence and incompetent calf perforators, impede orientation in venous hemodynamics. Venous pressure difference arising between the popliteal and the posterior tibial vein during the activity of the calf muscle venous pump was reported for the first time about 50 years ago, but regrettably, this important discovery continues to be unrespected. The venous pressure difference has since been termed ambulatory pressure gradient and seems to be the key factor triggering the venous reflux in the lower limb as well as the process leading to varicose vein recurrence. On the other hand, simultaneous recordings of the mean venous pressure in the posterior tibial and long saphenous veins demonstrated that the pressure curves have been identical at rest, during ambulation, and in the recovery period, a finding typical of conjoined vessels. Bidirectional flow within calf perforators taking place both in healthy subjects and in patients with varicose veins enables a quick equilibration of pressure changes between deep and superficial veins of the lower leg. Reflux disturbing the venous hemodynamics is in various degrees dependent on the quantity of retrograde flow; abolition of reflux restores normal venous hemodynamics. Reflux in superficial veins, if large enough, may cause the most severe form of chronic venous insufficiency. Femoral vein incompetence and incompetent calf perforators per se do not produce ambulatory venous hypertension and do not cause hemodynamic disturbance. This study discusses the controversial issues, tries to define and appraise the principal hemodynamic phenomena (ambulatory venous hypertension, ambulatory pressure gradient, venous reflux, superficial and deep vein incompetence, incompetent perforators), mentions a possible relation between deep vein incompetence and varicose veins, and attempts to present, based on proved facts, a comprehensive picture of the venous hemodynamics in the lower extremity.
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