Abstract

Ischemic preconditioning (IPC) is valid technique which elicits reductions in femoral blood flow occlusion mediated reperfusion stress (oxidative stress, Hsp gene transcripts) within the systemic blood circulation and/or skeletal muscle. It is unknown whether systemic hypoxia, evoked by hypoxic preconditioning (HPC) has efficacy in priming the heat shock protein (Hsp) system thus reducing reperfusion stress following blood flow occlusion, in the same manner as IPC. The comparison between IPC and HPC being relevant as a preconditioning strategy prior to orthopedic surgery. In an independent group design, 18 healthy men were exposed to 40 min of (1) passive whole-body HPC (FiO2 = 0.143; no ischemia. N = 6), (2) IPC (FiO2 = 0.209; four bouts of 5 min ischemia and 5 min reperfusion. n = 6), or (3) rest (FiO2 = 0.209; no ischemia. n = 6). The interventions were administered 1 h prior to 30 min of tourniquet derived femoral blood flow occlusion and were followed by 2 h subsequent reperfusion. Systemic blood samples were taken pre- and post-intervention. Systemic blood and gastrocnemius skeletal muscle samples were obtained pre-, 15 min post- (15PoT) and 120 min (120PoT) post-tourniquet deflation. To determine the cellular stress response gastrocnemius and leukocyte Hsp72 mRNA and Hsp32 mRNA gene transcripts were determined by RT-qPCR. The plasma oxidative stress response (protein carbonyl, reduced glutathione/oxidized glutathione ratio) was measured utilizing commercially available kits. In comparison to control, at 15PoT a significant difference in gastrocnemius Hsp72 mRNA was seen in HPC (−1.93-fold; p = 0.007) and IPC (−1.97-fold; p = 0.006). No significant differences were observed in gastrocnemius Hsp32 and Hsp72 mRNA, leukocyte Hsp72 and Hsp32 mRNA, or oxidative stress markers (p > 0.05) between HPC and IPC. HPC provided near identical amelioration of blood flow occlusion mediated gastrocnemius stress response (Hsp72 mRNA), compared to an established IPC protocol. This was seen independent of changes in systemic oxidative stress, which likely explains the absence of change in Hsp32 mRNA transcripts within leukocytes and the gastrocnemius. Both the established IPC and novel HPC interventions facilitate a priming of the skeletal muscle, but not leukocyte, Hsp system prior to femoral blood flow occlusion. This response demonstrates a localized tissue specific adaptation which may ameliorate reperfusion stress.

Highlights

  • Tourniquets are used in several surgical procedures (Fitzgibbons et al, 2012)

  • When compared to CON at 15 min posttourniquet removal (15PoT) muscle Hsp72 was lower in HPC intervention (HPCI) and IPC intervention (IPCI), both demonstrating large effect sizes (1.90 and 2.19, respectively) (Figure 3)

  • In agreement with the presented hypothesis it is a novel experimental finding that both IPCI and HPCI primed the localized heat shock protein (HSP) system producing a blunted response in Hsp72 mRNA post (15PoT) 30 min total knee replacement (TKR) like femoral blood flow occlusion compared to CON (Figure 3)

Read more

Summary

Introduction

Relative to total knee replacement (TKR) surgery their use facilitates a near bloodless field, improving visualization of crucial structures, and accelerating the surgical procedure (Smith and Hing, 2010; Estebe et al, 2011). Tourniquet mediated side-effects are not restricted to solely tissue damage (via direct tourniquet tissue compression), and through ischemic reperfusion (IR) mediated metabolic disruption (Fitzgibbons et al, 2012). Reperfusion of occluded tissue (i.e., the leg after TKR specific tourniquet use) may lead to ischemic injury with activated leukocytes increasing reactive oxygen species (ROS) and/or free-radical formation, resulting in transient elevations in oxidative stress (OS, Grace, 1994). ROS are essential for normal cellular signaling (Ray et al, 2012) and demonstrate an association with hormesis (Radak et al, 2008), a rapid increase in ROS can disrupt redox balance, resulting in OS induced protein denaturation and lipid oxidation (Halliwell and Chirico, 1993; Hawkins and Davies, 2001)

Objectives
Results
Conclusion
Full Text
Published version (Free)

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call