Abstract
Purpose: It is well established that skeletal muscle ischemia followed by reperfusion induces oxidative damage, metabolic stress, and an inflammatory response. This ischemia-reperfusion injury has been studied extensively in experimental models and, importantly, in the clinical setting where it is associated with tourniquet (TQ) inflation during orthopedic trauma surgery. Of particular clinical concern is the notion that reperfusion upon TQ release is central to oxidative injury, since release necessarily follows surgery. Consequently, the effects of ischemia alone, without reperfusion, is poorly documented. That is, it remains unknown what are the effects of muscle ischemia, per se, on muscle properties that could influence functional recovery postoperatively or what preventative measures might be taken to minimize the potentially deleterious effects of the ischemic period alone. Hence the purpose of this study was to investigate changes in myofibrillar contractile protein oxidation over the course of TQ-induced leg muscle ischemia during orthopedic trauma surgery.
Method: Among patients with unilateral ankle fractures requiring surgery at our institution, 24 subjects gave informed consent to participate. All subjects underwent standard general anesthesia. PRE surgical biopsies were collected from the peroneus tertius muscle (PT) immediately after TQ inflation and incision of the skin and underlying connective tissue. POST surgical biopsies were collected from the same muscle immediately before TQ release. Oxidation of PT myosin, actin, and total protein was quantified using Western blot analysis for 4-hydroxynonenal (4-HNE) modified proteins. Results are reported as mean ± standard deviation.
Results: Total TQ time ranged from about 21 to 84 min (50.5±16). As anticipated, in PRE biopsies compared to POST biopsies there were large increases in the PT content of 4-NE modified myosin (174.4±128%; P< 1×10-6), actin (223.7±182%; P< 5×10-9), and total protein (567.5±378%; P< 5×10-7). Intriguingly, there was a much greater increase in PT protein oxidation in males than in females (43.3% difference; P< 0.05), although there was no relationship observed between PT protein oxidation and subject age. Surprisingly, there was no significant relationship between muscle protein oxidation and duration of the TQ-induced ischemia.
Conclusion: TQ-induced skeletal muscle ischemia for 21 to 84 min during orthopedic trauma surgery leads to considerable oxidative muscle injury as measured by muscle protein oxidation, including of the functionally relevant contractile proteins myosin and actin. This injury occurs even without reperfusion. Interestingly, the extent of oxidative muscle injury appears to be influenced by gender, but is not dependent upon the duration of ischemia.
FUNDING: MSFHR, COF, BCLA.
Correspondence should be addressed to: COA, 4150 Ste. Catherine St. West Suite 360, Westmount, QC H3Z 2Y5, Canada. Email: meetings@canorth.org
