Summary
Stress proteins represent a group of highly conserved intracellular proteins that
provide adaptation against cellular stress. The present study aims to elucidate the
stress protein-mediated effects of local hyperthermia and systemic administration
of monophosphoryl lipid A (MPL) on oxygenation, metabolism and survival in bilateral
porcine random pattern buttock flaps. Preconditioning was achieved 24 h prior to surgery by applying a heating blanket on the operative site (n=5), by intravenous administration of MPL at a dosage of 35 μg/kg body weight (n=5) or by combining the two (n=5). The flaps were monitored with laser Doppler flowmetry, polarographic microprobes
and microdialysis until 5 h postoperatively. Semiquantitative immunohistochemistry was performed for heat shock
protein 70 (HSP70), heat shock protein 32 (also termed haem oxygenase-1, HO-1), and
inducible nitrc oxide synthase (iNOS). The administration of MPL increased the impaired
microcirculatory blood flow in the proximal part of the flap and partial oxygen tension
in the the distal part by ∼100% each (both P<0.05), whereas both variables remained virtually unaffected by local heat preconditioning.
Lactate/pyruvate (L/P) ratio and glycerol concentration (representing cell membrane
disintegration) in the distal part of the flap gradually increased to values of ∼500 mmol/l and ∼350 μmol/l, respectively (both P<0.01), which was substantially attenuated by heat application (P<0.01 for L/P ratio and P<0.05 for glycerol) and combined preconditioning (P<0.01 for both variables), whereas the effect of MPL was less marked (not significant).
Flap survival was increased from 56% (untreated animals) to 65% after MPL (not significant),
71% after heat application (P<0.05) and 78% after both methods of preconditioning (P<0.01). iNOS and HO-1 were upregulated after each method of preconditioning (P<0.05), whereas augmented HSP70 staining was only observed after heat application (P<0.05). We conclude that local hyperthermia is more effective in preventing flap necrosis
than systemic MPL administration because of enhancing the cellular tolerance to hypoxic
stress, which is possibly mediated by HSP70, whereas some benefit may be obtained
with MPL due to iNOS and HO-1-mediated improvement in tissue oxygenation.
Keywords
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References
- Dual preconditioning: effects of pharmacological plus ischemic preconditioning on skin flap survival.Ann Plast Surg. 2003; 50: 398-402
- Preconditioning of the distal portion of a rat random-pattern skin flap.Br J Plast Surg. 2001; 54: 58-61
- The role of iNOS in chronic inflammatory processes in vivo: is it damage-promoting, protective, or active at all?.Curr Mol Med. 2004; 7: 763-775
- HSP 70 chaperones, cellular functions and molecular mechanism.Cell Mol Life Sci. 2005; 62: 670-684
- The heme oxygenase system: a regulator of second messenger gases.Annu Rev Pharmacol Toxicol. 1997; 37: 517-554
- Endogenous nitric oxide synthesis: biological functions and pathophysiology.Free Radic Res. 1999; 6: 577-596
- Regulation of the heat shock transcriptional response: cross talk between a family of heat shock factors, molecular chaperones, and negative regulators.Genes Dev. 1998; 24: 3788-3796
- Improved skin flap survival after local heat shock preconditioning in pigs.J Surg Res. 2004; 119: 100-105
- Preconditioning with Monophosphoryl Lipid A improves survival of critically ischemic tissue.Anesth Analg. 2005; 100: 1786-1792
- Preconditioning of latissimus dorsi muscle flaps with monophosphoryl lipid A.Plast Reconstr Surg. 2003; 111: 267-274
- Additive effects of late preconditioning produced by monophosphoryl lipid A and the early preconditioning mediated by adenosine receptors and KATP channel.Circulation. 1999; 99: 3003-3007
- Pretreatment of normal humans with monophosphoryl lipid A induces tolerance to endotoxin: a prospective, double-blind, randomized, controlled trial.Crit Care Med. 1995; 23: 9-17
- The influence of trauma and ischemia on carbohydrate metabolites monitored in hamster flap tissue.Anesth Analg. 2005; 100: 817-822
- Acute normovolemic hemodilution improves oxygenation in ischemic flap tissue.Anesthesiology. 2002; 96: 1478-1484
- Microwave-stimulated antigen retrieval is pH and temperature dependent.J Histochem Cytochem. 1994; 12: 1555-1563
- Antigenic heterogeneity of vascular endothelium.Am J Pathol. 1992; 141: 673-683
- Regional variations of laser Doppler blood flow in ischemic skin flaps.Plast Reconstr Surg. 1990; 86: 319-326
- Monophosphoryl lipid A attenuates the effects of endotoxic shock in pigs.J Lab Clin Med. 1992; 119: 346-353
- The late phase of preconditioning.Circ Res. 2000; 87: 972-983
- Essential role of inducible nitric oxide synthase in monophosphoryl lipid A-induced late cardioprotection: evidence from pharmacological inhibition and gene knockout mice.Circulation. 1999; 99: 2157-2163
- Role of inducible nitric oxide synthase in pharmacological “preconditioning” with monophosphoryl lipid A.J Mol Cell Cardiol. 1997; 29: 1567-1576
- The heme oxygenase-1 pathway is involved in calcitonin gene-related peptide-mediated delayed cardioprotection induced by monophosphoryl lipid A in rats.Regul Pept. 2002; 103: 1-7
- Inducible nitric oxide synthase (iNOS) activity promotes ischaemic skin flap survival.Br J Pharmacol. 2001; 132: 1631-1638
- The effects of L-arginine and iloprost on the viability of random skin flaps in rats.Scand J Plast Reconstr Surg Hand Surg. 1998; 32: 19-25
- Involvement of nitric oxide in survival of random pattern skin flap.Plast Reconstr Surg. 1998; 101: 785-792
- Smooth muscle cell-derived carbon monoxide is a regulator of vascular cGMP.Proc Natl Acad Sci USA. 1995; 92: 1475-1479
- Endothelial cell expression of vasoconstrictors and growth factors is regulated by smooth muscle cell-derived carbon monoxide.J Clin Invest. 1995; 96: 2676-2682
- Local heat shock priming-induced improvement in microvascular perfusion in osteomyocutaneous flaps is mediated by heat shock protein 32.Br J Surg. 2001; 88: 450-457
- Heat shock preconditioning reduces ischemic tissue necrosis by heat shock protein (HSP)-32-mediated improvement of the microcirculation rather than induction of ischemic tolerance.Ann Surg. 2005; 242: 869-878
- Overexpression of HSP-72 confers cytoprotection in experimental peritoneal dialysis.Kidney Int. 2004; 66: 2300-2307
- Hsp 72 induction: a potential molecular mediator of the delay phenomenon.Ann Plast Surg. 2000; 44: 65-71
- HSP70 and GRP78 induced by endothelin-1 pretreatment enhance tolerance to hypoxia in cultured neonatal rat cardiomyocytes.J Cardiovasc Pharmacol. 2004; 44: 117-120
- Effect of mutation of amino acids 246-251 (KRKHKK) in HSP72 on protein synthesis and recovery from hypoxic injury.Am J Physiol Heart Circ Physiol. 2005; 289: H2519-H2525
- Specific heat shock proteins protect microtubules during simulated ischemia in cardiac myocytes.Am J Physiol. 1998; 275: H2243-H2249
- Improving acute skin-flap survival through stress conditioning using heat shock and recovery.Plast Reconstr Surg. 1992; 44: 659-664
Article info
Publication history
Published online: April 13, 2007
Accepted:
February 20,
2007
Received:
July 23,
2006
Footnotes
☆Oral presentation at the 16th Annual EURAPS-Meeting in Marseilles, France, May 2005 (results partly presented).
Identification
Copyright
© 2007 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Inc. All rights reserved.