Reperfusion Injury

Definition- the tissue damage due to the return of blood supply to the tissue after a period of ischemia.

Mechanism (Pathophysiology of ischaemia-reperfusion injury; PubMed-NCBIPMID:10685060):-

♦Ischemia ⇒lack of oxygen & nutrients ⇒ restoration of circulation ⇒ oxidative stress ⇒ Inflammation & oxidative damage of the tissue.

♦Restoration of circulation ⇒ Leukocytes to the area ⇒ Release of Inflammatory mediators (cytokines, interleukins)⇒ Tissue damage
♦Restoration of circulation ⇒ free oxygen radicals to the tissue & cells ⇒ Damage to the tissue(damage of cellular proteins, DNA & plasma membrane)
♦Oxygen free radicals & Inflammatory mediators ⇒ act indirectly by signalling APOPTOSIS.

♦Leukocytes ⇒ bind to the endothelium of small capillaries ⇒ obstruction ⇒ More Ischemia.

♠Trauma & Crush Injury⇒Large amount of muscle involved in the ischemic process⇒systemic inflammatory response ⇒ e.g. acute compartment syndrome with crush syndrome. Pro-coagulants & myoglobin, potassium & phosphorus escape into the systemic circulation producing systemic coagulopathy with parallel activation of inflammatory mediators ⇒ damage of vascular endothelium ⇒Increased permeability ⇒Hypovolemic shock Hyperkalemia ⇒ Multi-organ failure.

Examples of reperfusion injury:- 1. Trauma of extremity with muscle break down & development of acute compartment syndrome, Crush injury & multiorgan failure; 2. Brain stroke, Brain trauma, Brain damage after reversal of cardiac arrest;  3. Repeated ischemia & reperfusion- failure of healing of chronic wounds e.g. Diabetic foot ulcers, Pressure sores, 4. Reperfusion injury in organ transplantation e.g. Liver transplantation, 5. Myocardial Infarction.

Reperfusion⇒Hyperkalemia

Prevention of Reperfusion injury: I. Ischemic preconditioning, II. Controlled, graded reperfusion,  III. Use of free radical scavengers IV. Use of agents like- Antioxidants, Antithromboxanes, Antileukotrienes, Anti-platelet-activating factors, Anticomplement, Antileukocytes; Adenosine in MI

Laboratory Investigations: Urine Myoglobin, Serum CPK, Serum electrolytes-K, Na, HCO3, Renal function- BUN, B. urea, S. creatinine, S. Uric Acid etc.

TREATMENT:- 1. Fluid Replacement– extensive muscle damage(rhabdomyolysis) causes massive fluid sequestration, can cause fatal hypovolemia & renal failure– to be corrected by giving adequate fluid.

2. Alkalinization of Urine: – Bicarbonates, Acetazolamide

3. Mannitol, scavengers of hydroxy free radicals, Allopurinol- protects against myocardial necrosis.

4. Amiloride, KCl sparing drugs- decreases intracellular Na-concentration & inhibits Na-H & Na-Ca exchange.

5. Avoid IV Calcium unless there is the danger of hyperkalemic arrythmia.