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العنوان
Study of Different Therapeutic Agents for the Prevention of Ischemia Reperfusion Injury in Free skin flaps:
المؤلف
Morsy, Mai Mosad Abd Elghany.
هيئة الاعداد
باحث / Mai Mosad Abd Elghany Morsy
مشرف / Ahmed Ali Hassan
مشرف / Ibrahim Husin Kamel
مناقش / Khaled Mohamed El Gazzar
تاريخ النشر
2018.
عدد الصفحات
129 P. :
اللغة
الإنجليزية
الدرجة
الدكتوراه
التخصص
الطب (متفرقات)
تاريخ الإجازة
1/1/2018
مكان الإجازة
جامعة عين شمس - كلية الطب - قسم جراحة التجميل والحروق والوجة والفكين
الفهرس
Only 14 pages are availabe for public view

from 129

from 129

Abstract

We have summarized current state of knowledge regarding the molecular and cellular events underlying I/R-mediated tissue injury, as well as strategies to overcome this type of injury. The events occurring during I/R injury included: neutrophil-mediated endothelial cytotoxicity and activation, generation of free radicals, triggering of cytokines and chemokines, and activation of adhesion molecules and the complement system. Evidence indicates that tissue damage is largely caused by activated neutrophils which accumulate when the tissue is reperfused.
Ischemia reperfusion injury is initiated by production of reactive oxygen species which initially appear responsible for the generation of chemotactic activity for neutrophils. Therapeutic options for limiting ischemia reperfusion injury include inhibition of oxygen radical formation, pharmacological prevention of neutrophil activation and chemotaxis, and also the use of monoclonal antibodies which prevent neutrophil-endothelial adhesion, a prerequisite for injury.
Primary ischemia begins when the vascular pedicle of a free flap is clamped. With cessation of blood flow, the flap becomes anoxic. Tissue oxygen levels decrease, and the intracellular metabolism changes from aerobic to anaerobic. In the presence of anaerobic metabolism, lactate accumulates, the pH of the cell drops, and availability of ATP is decreased to fuel ionic pumps. These changes impair membrane transport functions. Cellular metabolites concentrate within the cell. Intracellular calcium levels begin to rise and proinflammatory mediators accumulate.
Summary and conclusion
94
At the conclusion of primary ischemia, the structural and metabolic changes include:
(1) Narrowed capillary diameters caused by endothelial swelling, vasoconstriction, and interstitial edema.
(2) Sequestration of leukocytes poised to release proteolytic enzymes and reactive oxygen intermediates.
(3) Metabolic dysfunction of endothelial cells causing diminished ability to synthesize and release vasodilators and to degrade ambient vasoconstrictors.
(4) End-organ cell membrane dysfunction and accumulation of intracellular and extracellular toxins.
(5) Up-regulation of enzyme systems designed to produce inflammatory mediators.
With release of the vascular clamps, the period of reperfusion begins. The degree of injury incurred is influenced by many variables, including tissue type, temperature, time of ischemia, perfusion pressures, pharmacologic pretreatment, and physiologic preconditioning. Under favorable conditions, reperfusion restores normal blood flow and normal metabolic function to the flap.
Reperfusion injury is an inflammatory process modulated by the complex signaling mechanisms of the immune system. Reperfusion is essential for flap survival. Reperfusion injury occurs when restored blood flow allows the influx of inflammatory substrates that will ultimately destroy the flap. The transition point between normal reperfusion and reperfusion injury is poorly defined and differs among various tissue types and experimental conditions. When vascular clamps are released, two “zones” of injury must recover to allow successful reperfusion. The first zone of injury is the vascular anastomosis, where thrombosis is the
Summary and conclusion
95
main threat. The second zone of injury is the distal microcirculation and parenchyma of the flap itself.
The importance of the neutrophil in ischemia/ reperfusion injury has been recognized for many years. Neutrophils were once considered the “trigger” of ischemia/reperfusion injury. More recent work has characterized the neutrophil as the “bullet” or final pathway through which much of the destruction occurs. There is growing evidence of the importance of neutrophils in the production of charged oxygen species.
Neutrophils physiologically rely on lysosomes and charged oxygen species to destroy pathogens encountered by the immune system. In some inflammatory states (including ischemia/ reperfusion injury), these agents are directed against the host rather than a pathogen. When stimulated, activated neutrophils produce a “respiratory burst,” resulting in releases of large quantities of oxygen free radicals. The neutrophils also produce proteinases and phospholipases, which damage endothelial cells and vascular membranes leading to tissue edema and further thrombosis.
Secondary ischemia occurs after a free flap has been transplanted and reperfused. For various reasons (thrombosis, vasospasm, ischemia/ reperfusion injury), perfusion to the flap may be interrupted after the anastomoses have been completed and the flap reperfused. Surgeons and researchers have noted that this second period of ischemia is much more damaging to the flap than the initial ischemic episode. There was massive intravascular thrombosis in the flaps undergoing secondary ischemia. The weight of the flap (indicating interstitial edema) was significantly greater in the flaps undergoing secondary ischemia, and fibrinogen and platelet concentrations were increased in venous effluent.Apparently, the timing of these episodes of secondary ischemia is significant with respect to the degree of flap ischemia produced. In a study of skin flaps in experimental animals, when the interval between primary ischemia and secondary ischemia was 24 hours or less, secondary ischemia produced significantly more flap necrosis than primary ischemia alone. When the interval was stretched to 72 hours between the two ischemic episodes, flap survival was similar for secondary ischemia and primary ischemia.
A long list of therapeutic agents has been recommended to improve survival of revascularized free flaps. Anticoagulants, Thrombolytic agents, antiinflammatory agents, free radical scavengers, vasodilators, immunomodulation, and platelet-activating factor and arachidonic acid metabolites
After evaluation of the effect of monoclonal antibody to (ICAM 1) “LY-6G”, heparin, and free radicals scavengers (vit. C) in the prevention of ischemia reperfusion injury effect in free skin flap of a rat model, we found that The best result of flap survival compared to sham group were in group V (ly6g group) by 10% more necrosis only then group IV (heparin group) by14% then group III (vit.c group) by 23% more necrosis of flaps. The monoclonal antibody directed towards the neutrophils reducing accumulation into reperfused tissue and it was the most statistically significant result more than heparin and vitamin C.