CONTROLLED REPERFUSION REDUCES REPERFUSION INJURY IN SKELETAL-MUSCLE AFTER INCOMPLETE LIMB ISCHEMIA

Systemic and local complications occur after revascularization of extr emities exposed to prolonged complete ischemia. Recently the authors d emonstrated in experimental and clinical studies that these deleteriou s effects after normal blood (uncontrolled) reperfusion could be reduc ed significantly by controlling the composition of the reperfusate (ca lcium, pH, amino acids, osmolarity, and glucose) and the circumstances of the reperfusion (time, temperature, and pressure; controlled reper fusion) after complete prolonged limb ischemia. In this study the auth ors test the hypothesis that controlled reperfusion also has a benefic ial effect and is safe to apply after a period of six hours of incompl ete limb ischemia. Ten adult German house swine were exposed to six ho urs of incomplete limb ischemia by occlusion of the left iliac artery. This resulted in a significant reduction of limb tissue temperature ( P < 0.0003, ANOVA), pH, (P < 0.0003, ANOVA), and adenosine triphosphat e (ATP) (P < 0.0003, ANOVA), as well as in increased levels of creatin e kinase (CK) in the systemic venous (P < 0.003, ANOVA) and in the fem oral vein blood (P < 0.03 ANOVA). To simulate the clinical situation o f embolectomy in 5 pigs the authors released the occlusive snares afte r the ischemic period and let the normal blood flow with systemic pres sure occur (uncontrolled reperfusion). In the other 5 pigs (controlled reperfusion) they delivered a controlled reperfusate by withdrawing b lood from the aorta and mixing it with a crystalloid solution (calcium reduced, hyperosmolaric, hyperglycemic, alkalotic, glutamate and aspa rtate enriched, and containing a free radical scavenger) under control led conditions (ratio blood:crystalloid solution 6:1, for thirty minut es, reperfusion pressure < 50 mmHg, and normothermia) before establish ing normal blood reperfusion. During the initial reperfusion (measured at five minutes after start of reperfusion) the group with controlled reperfusion (as compared with the animals with uncontrolled reperfusi on) showed higher oxygen consumption (32.7 +/- 3.4 vs 15.8 +/- 1.9 mL/ 100g/min, P < 0.01, ANOVA), higher glucose consumption (439.0 +/- 115. 7 vs 16.5 +/- 4.7 mg/100g/min, P < 0.03, ANOVA), less vascular resista nce (19.2 +/- 2.8 vs 31.4 +/- 2.1 dyn x sec/cm5, P < 0.03, ANOVA) as w ell as less lactate dehydrogenase (LDH; 286.2 +/- 38.2 vs 604.6 +/- 30 .7 U/L, P < 0.0003, ANOVA) and creatine kinase (CK; 294.2 +/- 73.0 vs 602.8 +/- 85.5 U/L, P < 0.03, ANOVA) concentration in the femoral vein blood. At the end of the observation period (measured at ninety minut es after start of reperfusion), the group with controlled reperfusion showed less tissue water content (81.8 +/- 0.7 vs 84.3 +/- 0.7%, P < 0 .05, ANOVA), higher tissue ATP content (17.0 +/- 2.4 vs 9.7 +/- 4.3 mu Mol/g protein, ns), higher tissue ATP increase as compared with end is chemic values (6.1 +/- 1.5 vs -2.5 +/- 1.8 muMol/g protein, P < 0.03, ANOVA), higher tissue pH (7.2 +/- 0.1 vs 6.8 +/- 0.1, P < 0.03, ANOVA) , less temperature decrease (0.3 +/- 0.2 vs 1.2 +/- 0.3-degrees-C, P < 0.05, ANOVA), less reduction of flow in the limb (0.2 +/- 0.2 vs -1.3 +/- 0.4 mL/100g/min, P < 0.03, ANOVA), less vascular resistance (16.7 +/- 1.2 vs 22.8 +/- 1.5 dyn x seC/cm5, p < 0.03, ANOVA), less CK (355 .0 +/- 87.5 vs 624.4 +/- 73.4 U/L, P < 0.05, ANOVA) and LDH (369.5 +/- 42.5 vs 538.4 +/- 39.1 U/L, P < 0.03, ANOVA) concentration in the fem oral vein blood as well as less CK (335.0 +/- 89.0 vs 595.8 +/- 76.6, P < 0.05) and LDH (356.5 +/- 48.9 vs 546.0 +/- 37.8 U/L, P < 0.0003, A NOVA) concentration in the central venous blood. These data indicate t hat severe local and systemic damage occurs with uncontrolled (normal blood) reperfusion even after incomplete limb ischemia and that these reperfusion changes can be reduced significantly by delivering a contr olled reperfusate under controlled conditions without any observable n egative side effects. They confirm the results with controlled limb re perfusion after prolonged complete limb ischemia (aortic occlusion), a nd this concept has already been successfully applied in 15 patients w ith complete and incomplete limb ischemia as long as eighteen hours.