Reperfusion damage
As a reperfusion injury , a disease process is referred to by the restored blood flow after a more or less long-lasting reduced blood flow ( ischemia ) of a limb (. Eg as a result of the tourniquet syndrome ) or an organ is triggered. The term reperfusion paradox describes the apparent contradiction that renewed blood flow can lead to additional damage.
Occurrence
Reperfusion damage occurs in various medical specialties and each has its own clinical significance.
In transplant medicine , reperfusion damage is caused by blood circulation in the transplant . As a result, rejection reactions , organ failure and damage to the entire organism through toxic reactions can occur.
In cardiology , reperfusion damage occurs in the treatment of acute myocardial infarction , for example through PTCA , thrombolysis or stent implantation .
In vascular surgery , the revascularization of an occlusion of an arterial flow area leads to reperfusion damage, the extent of which depends not only on the duration of the occlusion, but above all on its location.
In traumatology , reperfusion damage occurs mainly after injury to large arteries of the extremities.
The cause of ischemia can be an acute arterial occlusion ( embolism ), a vascular injury in the context of trauma or prolonged compression of the supplying artery from the outside (ligature, tourniquet).
Clinical picture
Clinically, there is general tissue damage in the affected part of the body as well as over- acidosis ( acidosis ) of the entire organism. This locally leads to overheating, reddening and swelling of the affected area, on the leg or arm up to the development of a compartment syndrome with extensive rhabdomyolysis . In general terms , the symptoms can range from a slight acceleration in spontaneous breathing ( tachypnea ) to a drop in blood pressure , cardiac arrhythmias as a result of hyperkalemia , coagulation disorders, kidney failure or even cardiovascular arrest. The severity of the reperfusion damage depends directly on the duration of the ischemia and the extent of the ischemic region of the body. The most difficult of the reperfusion injury is after longer existing acute Leriche syndrome (closure of the lower abdominal aorta - abdominal aorta - by "riding" thrombus in the branching in the pelvic arteries).
Pathophysiology
The pathophysiological process that leads to reperfusion damage develops as follows:
The oxygen deficiency during ischemia leads to an almost complete breakdown of ATP , the cell's universal energy supplier , within a few minutes , which leads to an increase in hypoxanthine . At the same time, due to the functional stop of the ATP-dependent ion transporter , potassium outflow and calcium influx occur . This and the increase of hypoxanthine result in conversion of the enzyme xanthine dehydrogenase to xanthine oxidase , which comprises hypoxanthine in the presence of oxygen at again successful reperfusion xanthine oxidized . The free oxygen radicals produced during this conversion, such as superoxide , hydrogen peroxide or hydroxyl radicals , can damage cell membranes through lipid peroxidation and thus contribute to the progression of the damage caused by the previous blood evacuation.
In addition to these direct cell-damaging effects, oxygen radicals above all also stimulate neutrophilic granulocytes and also the formation of adhesion molecules . The result is an increased binding of the white blood cells to the endothelium of the smaller blood vessels and the migration of these white blood cells into the surrounding tissue. There, stimulated neutrophil granulocytes, in turn, can in turn release large amounts of oxygen radicals and, in some cases, even aggressive messenger substances such as platelet-activating factor (PAF) or leukotrienes . This stimulates new white blood cells that build up in damaged tissue.
This chain of reactions can create a self-sustaining vicious circle with the constant formation of new oxygen radicals and stimulation of the white blood cells. The release of cell-damaging granules and the formation of aggressive oxygen metabolic intermediates cause further tissue damage, a massive increase in the permeability of the endothelium and a further increase in edema . In addition to the increasing tissue pressure, which can represent a considerable hindrance to the re-flow of blood, the enlargement of the flow path through the tissue also leads to a deterioration of the metabolic situation, which is over-acidified due to insufficient blood flow, and thus to an increase in tissue damage.
In addition to selectins, which mainly mediate the first contact between the white blood cells and the vascular endothelium, VCAM-1 ( vascular cell adhesion molecule 1 ) and above all ICAM-1 ( intercellular adhesion molecule 1 ) turned out to be the most important adhesion molecules that cause the white cells to migrate Blood cells are necessary through the vascular endothelium.
If the blood flow to the tissue is restored, i.e. new oxygen is available for oxidative reactions, the conversion of hypoxanthine to xanthine begins, with massive free oxygen radicals being formed, which further damage the tissue.
treatment
This process cannot be prevented with current medical means, but the activity of the enzymes can be reduced by cooling the affected tissue before reperfusion . This leads to a slower production of the dangerous oxygen radicals and can thus reduce tissue damage. Since the reperfusion damage usually occurs during the surgical procedure to correct the ischemia , the anesthetist can counteract the metabolic acidosis directly by hyperventilation (development of respiratory alkalosis ). In more severe cases, the acidosis must also be "buffered" with sodium bicarbonate . In addition, circulatory drugs ( catecholamines ) and diuretics may be used. In connection with reperfusion damage during ventilation of COVID-19 patients, experts are now also reporting positive experiences with enriching the ventilation air with molecular hydrogen H 2, which neutralizes the reactive oxygen species, or oxyhydrogen ("Brown's gas", HHO).
swell
- Brigitte Marian: Illness, causes and symptoms of illness. Facultas University Press; Edition: 1 (October 2007). ISBN 3-7089-0183-5
- Local Heat Shock - A conditioning procedure used to reduce the inflammatory response and improve microvascular perfusion in transferred osteomyocutaneous flaps; Dissertation by Thilo Johannes Schäfer (2006)
