Late-Preconditioning Protection is Evident in the Microcirculation of Denervated Skeletal Muscle

Abstract

Summary:We investigated whether ischemic preconditioning induces microvascular protection in skeletal muscle at the late phase (after 24 hours) when the same muscles are subjected to prolonged warm global ischemia. The cremaster muscle of the male Sprague-Dawley rat underwent vascular isolation and was subjected to 4 hours of ischemia and 60 minutes of reperfusion. Early preconditioning consisted of 45 minutes of ischemia followed by 15 minutes of reperfusion before prolonged ischemiaireperfusion; late preconditioning also consisted of 45 minutes of ischemia but was done 24 hours (24-hour period of reperfusion) before the prolonged ischemiaireperfusion. Arteriole diameters and capillary perfusion were measured with use of intravital microscopy. Four groups were compared: rats that underwent early preconditioning, their controls, rats that underwent late preconditioning, and their controls. Early and late preconditioning significantly attenuated vasospasm and capillary no-reflow compared with the controls for each. Average arteriole diameter was significantly larger in the rats that underwent late preconditioning than in any other rats; it was also significantly larger in the controls for late preconditioning than in those for early preconditioning. We introduce a model of the rat cremaster muscle that has been isolated from its vascular supply as a useful preparation to study the effects of late preconditioning on microcirculation in skeletal muscle. Late preconditioning provided better microvascular protection than did early preconditioning. The mechanism for this preconditioning protection is being investigated because it should provide a means for therapeutic intervention.Protecting skeletal muscle from injury due to ischemia/reperfusion has been a goal in orthopaedic surgery for many years. Except for early restoration of blood flow to the area at risk for muscle necrosis, little else can be used as a direct therapeutic intervention. 'Typical problems include the replantation of amputated limbs, free muscle-flap transfer, posttraumatic compartment syndrome, Volkmann's ischemic contracture, and embolism or thrombosis of major blood vessels.As early as 1968, Ames et al. (1) demonstrated that if the blood flow to a rabbit brain is interrupted for 5 minutes or longer and then restored, certain areas will continue to remain ischemic; this i s the so-called "noretlow phenomenon." showed that four of six rats had no arterial blood flow in the pedicle of the anterior tibialis muscle after 5 hours of ischemia produced by clamping the common iliac and femoral arteries. Korthuis el al. (9) demonstrated a %fold increase in vascular resistance in the

Near infrared spectroscopy (NIRS) to assess the effects of local ischemic preconditioning in the muscle of healthy volunteers and critically ill patients

“…Data investigating the effects of ischemic preconditioning on the microcirculation have shown that it prevents microcirculatory vasoconstriction and no-flow events after a later ischemic event (Wang et al, 1996;Wang et al, 1999), but the acute effects of ischemic preconditioning on microvascular density have not been well studied. NIRS monitoring enables quantification of the oxy-and deoxy-hemoglobin contents, in a fixed area of tissue (dependent on the distance between the optodes), and the sum of these values is given as the THI (Mancini et al, 1994).…”

Late‐phase ischemic preconditioning in skeletal muscle: is the phenomenon protective?

“…9À11 Each study used a different IPC protocol: two used the same ischemic challenge, and one reported a controversial result. Pudupakkam et al 10 preconditioned with five 10-min cycles of ischemia/reperfusion and challenged muscles with a 2-h ischemic insult, while Wang et al 11 used a single 45-min cycle of ischemia/reperfusion and challenged muscles with a 4-h ischemic insult. Both studies prevented the no-reflow phenomenon and attenuated vasospasm during reperfusion.…”

Therapeutic Interventions Against Reperfusion Injury in Skeletal Muscle

“…However, it is the late phase that provides protection during the period when most microsurgical problems usually arise. We have reported that microcirculatory alterations do not take place in rat cremaster muscle if 4 h of warm ischemia is preceded by IPC [54][55][56][57][58][59][60]. We have conducted several studies investigating the mechanisms of late preconditioning.…”