Ischemic preconditioning-induced microvascular protection at a distance

Ischemic preconditioning-induced microcirculatory protection appears to be a systemic rather than a local phenomenon. This protection induced by remote ischemic preconditioning (RIPC) may be attributed to a humoral rather than a neuronal mechanism. An innervated (Inn, Groups 1 and 4) or denervated (Den, Groups 2 and 3) and vascular isolated right cremaster of the rat was prepared. Left femoral vessels were clamped (Groups 1, 2, and 4) for 45 min or unclamped (Group 3) as a control. After 2 hr of reperfusion in the left lower extremity, 4 hr of ischemia in the right cremaster was applied in Groups 1, 2, and 3. However, in Group 4, 4 hr of ischemia in the cremaster muscle was instituted before reperfusion of the left femoral artery was begun. Microcirculatory responses, including terminal arteriole diameter, capillary perfusion, and endothelium function were evaluated. Four groups (six rats per group) were designed: Group 1: RIPC (Inn); Group 2: RIPC (Den); Group 3: sham RIPC (Den); and Group 4: fake RIPC (Inn). Ischemia of 45 min followed by 2 hr of reperfusion in the left lower extremity of the rat induced a significant microvascular protection against subsequent 4-hr ischemia in both innervated and denervated cremasters. This microvascular protection at a distance was lost in sham RIPC and in fake RIPC groups. The results demonstrated that remote protection induced by ischemic preconditioning is a systemic phenomenon and due to a humoral mechanism.