The role of tendon microcirculation in Achilles and patellar tendinopathy

Karsten Knobloch, Karsten Knobloch

Abstract

Tendinopathy is of distinct interest as it describes a painful tendon disease with local tenderness, swelling and pain associated with sonographic features such as hypoechogenic texture and diameter enlargement. Recent research elucidated microcirculatory changes in tendinopathy using laser Doppler flowmetry and spectrophotometry such as at the Achilles tendon, the patellar tendon as well as at the elbow and the wrist level. Tendon capillary blood flow is increased at the point of pain. Tendon oxygen saturation as well as tendon postcapillary venous filling pressures, determined non-invasively using combined Laser Doppler flowmetry and spectrophotometry, can quantify, in real-time, how tendon microcirculation changes over with pathology or in response to a given therapy. Tendon oxygen saturation can be increased by repetitive, intermittent short-term ice applications in Achilles tendons; this corresponds to 'ischemic preconditioning', a method used to train tissue to sustain ischemic damage. On the other hand, decreasing tendon oxygenation may reflect local acidosis and deteriorating tendon metabolism. Painful eccentric training, a common therapy for Achilles, patellar, supraspinatus and wrist tendinopathy decreases abnormal capillary tendon flow without compromising local tendon oxygenation. Combining an Achilles pneumatic wrap with eccentric training changes tendon microcirculation in a different way than does eccentric training alone; both approaches reduce pain in Achilles tendinopathy. The microcirculatory effects of measures such as extracorporeal shock wave therapy as well as topical nitroglycerine application are to be studied in tendinopathy as well as the critical question of dosage and maintenance. Interestingly it seems that injection therapy using color Doppler for targeting the area of neovascularisation yields to good clinical results with polidocanol sclerosing therapy, but also with a combination of epinephrine and lidocaine.

Figures

Figure 1
Figure 1
Oxygen-to-see probe, a combined laser Doppler and spectrophotometry system to determine Achilles microcirculation non-invasively.
Figure 2
Figure 2
Oxygen-to-see system combining Laser Doppler flowmetry and spectrophotometry non-invasively to determine tendon capillary blood flow, tendon oxygen saturation, and tendon postcapillary venous filling pressures.
Figure 3
Figure 3
Capillary tendon blood flow in mid-portion symptomatic Achilles tendinopathy (left tendon) vs. the corresponding asymptomatic contralateral Achilles tendon in 50 patients with Achilles mid-portion tendinopathy.
Figure 4
Figure 4
Superficial (upper numbers [rE as arbitrary unit]) and deep (lower numbers) capillary flow at the second postoperative day following minimal invasive percutaneous Achilles tendon repair at the left leg.
Figure 5
Figure 5
Myocardial oxygen saturation (SO2%) following 5 min (red), 15 min (yellow) and 30 min (green) of ischemia following clamping of the left descending coronary artery and reperfusion with decreased baseline myocardial oxygen saturation after 15 and 30 min of ischemia indicating an ischemia-induced damage to the myocardium (Knobloch K, unpublished data).
Figure 6
Figure 6
Myocardial oxygenation following preconditioning with 2 min of repetitive ischemia/reperfusion (I/R) following clamping of the left descending coronary artery in humans (Knobloch K, unpublished data)
Figure 7
Figure 7
Achilles tendon capillary blood flow at 2 mm depth before (left) and after (right) 12 weeks of daily painful eccentric training in chronic Achilles tendinopathy among 59 patients with symptomatic 64 tendons.
Figure 8
Figure 8
Achilles tendon oxygen saturation before (left) and after (right) 12 weeks of daily painful eccentric training in chronic Achilles tendinopathy in 59 patients with symptomatic 64 tendons.
Figure 9
Figure 9
Oxygen-to-see system to determine capillary blood flow, tendon oxygen saturation and tendon postcapillary venous filling pressures non-invasively using combined Laser Doppler flowmetry and spectrophotometry.
Figure 10
Figure 10
Proposed flow chart of tendon degeneration starting with the healthy Achilles tendon and extrinsic a nd/or intrinsic factors over asymptomatic states with increase in tendon diameter and detectable capillary blood flow and/or Power Doppler flow to symptomatic states and consecutive tendon rupture. Created by Knobloch with accomplishments to Richards et al. 2005, Maffuli et al. 2000, Kannus et Josza 1991.

References

    1. Szomor ZL, Appleyard RC, Murrel GA. Overexpression of nitric oxide synthases in tendon overuse. J Orthop Res. 2006;24:80–6. doi: 10.1002/jor.20009.
    1. Uchio Y, Ochi M, Ryoke K, Sakai Y, Ito Y, Kuwata S. Expression of neuropeptides and cytokines at the extensor carpi radialis brevis muscle origin. J Shoulder Elbow Surg. 2002;11:570–5. doi: 10.1067/mse.2002.126769.
    1. Ljung BO, Alfredson H, Forsgren S. Neurokinin 1-receptors and sensory neuropeptides in tendon insertions at the medial and lateral epicondyles of the humerus. Studies on tennis elbow and medial epicondylalgia. J Orthop Res. 2004;22:321–7. doi: 10.1016/S0736-0266(03)00183-9.
    1. Stern MD, Lappe DL, Bowen PD, et al. Continuous measurement of tissue blood flow by laser-Doppler spectroscopy. Am J Physiol. 1977;232:H441–8.
    1. Alfredson H, Öhberg L. Increased intratendinous vascularity in the early period after sclerosing injection treatment in Achilles tendinosis. A healing response? Knee Surg Sports Traumatol Arthrosc. 2006;14:399–401. doi: 10.1007/s00167-006-0720-7.
    1. Astrom M, Svensson H. Tendon blood flow assessed by laser Doppler flowmetry. Scand J Plast Reconstr Surg Hand Surg. 1991;25:213–5. doi: 10.3109/02844319109020621.
    1. Schultz RJ, Krishnamurthy S, Thelmo W, Rodriguez JE, Harvey G. Effects of varying intensities of laser energy on articular cartilage: A preliminary study. Lasers Surg Med. 1985;5:577–588. doi: 10.1002/lsm.1900050606.
    1. Shalabi A, Movin T, Krisstoffersen-Wiberg M, Aspelin P, Svensson L. Reliability in the assessment of tendon volume and intratendinous signal of the Achilles tendon on MRI: a methodological description. Knee Surg Sports Traumatol Arthrosc. 2005;13:492–8. doi: 10.1007/s00167-004-0546-0.
    1. Alfredson H, Ohberg L. Neovascularisation in chronic painful patellar tendinosis – promising results after sclerosing neovessels outside the tendon challenge the need for surgery. Knee Surg Sports Traumatol Arthrosc. 2005;13:74–80. doi: 10.1007/s00167-004-0549-x.
    1. Gisslen K, Alfredson H. Neovascularisation and pain in jumper's knee: a prospective clinical and sonographic study in elite junior volleyball players. Br J Sports Med. 2005;39:423–8. doi: 10.1136/bjsm.2004.013342. discussion 423–8.
    1. Uchio Y, Ochi M, Ryoke K, Sakai Y, Ito Y, Kuwata S. Expression of neuropeptides and cytokines at the extensor carpi radialis brevis muscle origin. J Shoulder Elbow Surg. 2002;11:570–5. doi: 10.1067/mse.2002.126769.
    1. Knobloch K, Spies M, Busch KH, Vogt PM. Sclerosing therapy and eccentric training in flexor carpi ulnaris tendinopathy in a tennis player. Br J Sports Med. 2007;41:920–1. doi: 10.1136/bjsm.2007.036558.
    1. Fowble VA, Vigorita VJ, Bryk E, Sands AK. Neovascularity in chronic posterior tibial tendon insufficiency. Clin Orthop Relat Res. 2006;450:225–30. doi: 10.1097/01.blo.0000218759.42805.43.
    1. Perry SM, McIlhenny SE, Hoffman MC, Soslowsky LJ. Inflammatory and angiogenic mRNA levels are altered in a supraspinatus tendon overuse animal model. J Shoulder Elbow Surg. 2005;14:79S–83S. doi: 10.1016/j.jse.2004.09.020.
    1. Lin J, Wang MX, Wei A, Zhu W, Diwan AD, Murrel GA. Temporal expression of nitric oxide synthase isoforms in healing Achilles tendon. J Orthop Res. 2001;19:136–42. doi: 10.1016/S0736-0266(00)00019-X.
    1. Alfredson H, Bjur D, Thorsen K, Lorentzon R, Sandstrom P. High intratendinous lactate levels in painful chronic Achilles tendinosis. An investigation using microdialysis technique. J Orthop Res. 2002;20:934–8. doi: 10.1016/S0736-0266(02)00021-9.
    1. Folkman J, Klagsbrun M. Angiogenic factors. Science. 1987;28:442–447. doi: 10.1126/science.2432664.
    1. Maffulli N, Barras V, Ewen SW. Light microscopic histology of achilles tendon ruptures. A comparison with unruptured tendons. Am J Sports Med. 2000;28:857–63.
    1. Zeisig E, Ohberg L, Alfredson H. Extensor origin vascularity related to pain in patients with Tennis elbow. Knee Surg Sports Traumatol Arthrosc. 2006;14:659–63. doi: 10.1007/s00167-006-0060-7. Epub 2006 Mar 23.
    1. Petersen W, Pufe T, Kurz B, Mentlein R, Tillmann B. Angiogenesis in fetal tendon development: spatial and temporal expression of the angiogenetic peptide vascular endothelial growth factor (VEGF) Anat Embryol. 2002;205:263–270. doi: 10.1007/s00429-002-0241-1.
    1. Pufe T, Petersen W, Tillmann B, Mentlein R. The angiogenic peptide vascular endothelial cell growth factor (VEGF) is expressed in fetal and ruptured tendons. Virchows Arch. 2001;439:579–585. doi: 10.1007/s004280100422.
    1. Shukunami C, Oshima Y, Hiraki Y. Chondromodulin-I and tenomodulin: a new class of tissue-specific angiogenesis inhibitors found in hypovascular connective tissues. Biochem Biophys Res Commun. 2005;333:299–307. doi: 10.1016/j.bbrc.2005.05.133.
    1. O'Reilly MS, Behm T, Sing Y, et al. Endostatin: an endogenous inhibitor of angiogenesis and tumor growth. Cell. 1997;88:277–285. doi: 10.1016/S0092-8674(00)81848-6.
    1. Neufeld G, Cohen T, Genginovitch S, Poltrak Z. Vascular endothelial growth factor and its receptors. FASEB J. 1999;13:9–22.
    1. Pufe T, Petersen W, Kurz B, Tsokos M, Tillmann B, Mentlein R. Mechanical factors influence the expression of endostatin – an inhibitor of angiogenesis – in tendons. J Orthop Res. 2003;21:610–616. doi: 10.1016/S0736-0266(02)00262-0.
    1. Pufe T, Petersen WJ, Mentlein R, Tillmann BN. The role of vasculature and angiogenesis for the pathogenesis of degenerative tendons disease. Scandinavian Journal of Medicine & Science in Sports. 2005;15:211–222. doi: 10.1111/j.1600-0838.2005.00465.x.
    1. Alfredson H, Thorsen K, Lorentzon R. In situ microdialysis in tendon tissue: high levels of glutamate, but not prostaglandin E2 in chronic Achilles tendon pain. Knee Surg Sports Traumatol Arthrosc. 1999;7:378–81. doi: 10.1007/s001670050184.
    1. Bjur D, Alfredson H, Forsgren S. The innervation pattern of human Achilles tendon: studies of the normal and tendinosis with markers for general and sensory innervation. Cell Tissue Res. pp. 210–6.
    1. Ljung BO, Alfredson H, Forsgren S. Neurokinin 1-receptors and sensory neuropeptides in tendon insertions at the medial and lateral epicondyles of the humerus. Studies on tennis elbow and medial epicondylalgia. J Orthop Res. 2004;22:321–7. doi: 10.1016/S0736-0266(03)00183-9.
    1. Danielson P, Alfredson H, Forsgren S. Distribution of general (PGP 9.5) and sensory (substance P/CGRP) innervations in the human patellar tendon. Knee Surg Sports Traumatol Arthrosc. 2006;14:125–32. doi: 10.1007/s00167-005-0636-7.
    1. Danielson P, Alfredson H, Forsgren S. Immunohistochemical and histochemical findings favoring the occurrence of autocrine/paracrine as well as nerve-related cholinergic effects in chronic painful patellar tendon tendinosis. Microsc Res Tech. 2007;70:908–11. doi: 10.1002/jemt.20495.
    1. Andersson G, Danielson P, Alfredson H, Forsgren S. Presence of substance P and the neurokinin-1 receptor in tenocytes of the human Achilles tendon. Regul Pept. 2008 Mar 4. doi:10.1016/j.regpep.2008.02.005.
    1. Danielson P, Andersson G, Alfredson H, Forsgren S. Marked sympathetic component in the perivasculr innervation of the dorsal paratendinous tissue of the arthroscopically treated tendinosis patients. Knee Surg Sports Traumatol Arthrosc. 2008 Apr 17. Doi 10.1007/s00167-008-0530-1.
    1. Ohberg L, Alfredson H. Effects on neovascularisatino behind the good results with eccentric training in chronic Achilles tendinosis? Knee Surg Sports Traumatol Arthrosc. 2004;12:465–70.
    1. Shalabi A, Kristoffersen-Wiberg M, Svensson L, Aspelin P, Movin T. Eccentric training of the gastrocnemius-soleus complex in chronic Achilles tendinopathy results in decreased tendon volume and intratendinous signal as evaluated by MRI. Am J Sports Med. 2004;32:1286–96. doi: 10.1177/0363546504263148.
    1. Shalabi A, Kristoffersen-Wiberg M, Aspelin P, Movin T. Immediate Achilles tendon response after strength training evaluated by MRI. Med Sci Sports Exerc. 2004;36:1841–6. doi: 10.1249/01.MSS.0000145450.75035.61.
    1. Knobloch K, Lichtenberg A, Pichlmaier M, Tomaszek S, Krug A, Haverich A. Palmar microcirculation after harvesting of the radial artery in coronary revascularisation. Ann Thorac Surg. 2005;80:918–21. doi: 10.1016/j.athoracsur.2005.03.104.
    1. Knobloch K, Kraemer R, Lichtenberg A, Jagodzinski M, Gosling T, Richter M, Krettek C. Microcirculation of the ankle after Cryo/Cuff application in healthy volunteers. Int J Sports Med. Int J Sports Med. 2006;27:250–5. doi: 10.1055/s-2005-865623.
    1. Stern MD. In vivo evaluatio of microcirculation by coherent light scattering. Nature. 1975;254:56–8. doi: 10.1038/254056a0.
    1. Stein V, Laprell H, Tinnemeyer S, Petersen W. Quantitative assesment of the intravascular volumen of the human Achilles tendon. Acta Orthop Scand. 2000;181:313–314.
    1. Astrom M, Svensson H. Tendon blood flow assessed by laser Doppler flowmetry. Scand J Plast Reconstr Surg Hand Surg. 1991;25:213–5. doi: 10.3109/02844319109020621.
    1. Astrom M, Westlin N. Blood flow in the human Achilles tendon assessed by laser Doppler flowmetry. J Orthop Res. 1994;12:246–52. doi: 10.1002/jor.1100120214.
    1. Knobloch K, Kraemer R, Lichtenberg A, Jagodzinski M, Gossling T, Richter M, Zeichen J, Hufner T, Krettek C. Achilles tendon and paratendon microcirculation in midportion and insertional tendinopathy in athletes. Am J Sports Med. 2006;34:92–7. doi: 10.1177/0363546505278705.
    1. Zantop T, Tillmann B, Petersen W. Quantitative assessment of blood vessels of the human Achilles tendon: an immunohistochemical cadaver study. Arch Orthop Trauma Surg. 2003;123:501–504. doi: 10.1007/s00402-003-0491-2.
    1. Petersen W, Pufe T, Pfrommer S, Tillmann B. Overload damage to the Achilles tendon: the importance of vascularization and angiogenesis. Orthopade. 2005;34:533–42. doi: 10.1007/s00132-005-0808-7.
    1. Graf J, Schneider U, Niethard FU. Microcirculation of the Achilles tendon and significance of the paratenon. A study with the plastination method. Handchir Mikrochir Plast Chir. 1990;22:163–6.
    1. Knobloch K, Lichtenberg A, Pichlmaier M, Mertsching H, Krug A, Klima U, Haverich A. Microcirculation of the sternum following harvesting of the left internal mammary artery. Thorac Cardiovasc Surg. 2003;51:255–9. doi: 10.1055/s-2003-43083.
    1. Knobloch K, Tomaszek S, Lichtenberg A, Karck M, Haverich A. Long-term palmar microcirculation after radial artery harvesting: an observational study. Ann Thorac Surg. 2006;81:1700–7. doi: 10.1016/j.athoracsur.2005.12.030.
    1. Stone KR, Bowman HF, Boland A, Steadman JR. Ligament and tendon oxygenation measurements using polarographic oxygen sensors. Arthroscopy. 1987;3:187–95.
    1. Eriksson E. In vivo microdialysis of painful Achilles tendinosis. Knee Surg Sports Traumatol Arthrosc. 1999;7:339. doi: 10.1007/s001670050176.
    1. Kubo K, Ikebukuro T, Tsunoda N, Kanehisa H. Noninvasive measures of blood volume and oxygen saturation of human Achilles tendon by red laser lights. Acta Physiol (Oxf) 2008 Feb 5. doi:10.1111/j.1748-1716.2008.01841.x.
    1. Knobloch K, Grasemann R, Jagodzinski M, Richter M, Zeichen J, Krettek C. Changes of Achilles mid-portion tendon mircocirculation after repietitive simultaneous cryotherapy and compression using a standardized cryo-compression device (Cryo/Cuff™) Am J Sports Med. 2006;34:1953–9. doi: 10.1177/0363546506293701.
    1. Knobloch K. Eccentric training in Achilles tendinopathy: is it harmful to tendon microcirculation? Br J Sports Med. 2007;41:e2. doi: 10.1136/bjsm.2006.030437. discussion e2.
    1. Knobloch K, Schreibmueller L, Meller R, Busch KH, Spies M, Vogt PM. Superior Achilles tendon microcirculation in tendinopathy among symptomatic female vs. male patients. Am J Sports Med. 2008;36:509–14. doi: 10.1177/0363546507309313.
    1. Jonsson P, Wahlstrom P, Ohbeg L, Alfredson H. Eccentric training in chronic painful impingement syndrome of the shoulder: results of a pilot study. Knee Surg Sports Traumatol Arthrosc. 2006;14:76–81. doi: 10.1007/s00167-004-0611-8. Epub 2005 May 5.
    1. Knobloch K, Kraemer R, Jagodzinski M, Zeichen J, Meller R, Vogt PM. Eccentric training decreases paratendon capillary blood flow and preserves paratendon oxygen saturation in chronic achilles tendinopathy. J Orthop Sports Phys Ther. 2007;37:269–276.
    1. Petersen W, Welp R, Rosenbaum D. Chronic Achilles tendinopathy: a prospective randomized study comparing the therapeutic effect of eccentric training, the AirHeel brace, and a combination of both. Am J Sports Med. 2007;35:1659–67. doi: 10.1177/0363546507303558. Epub 2007 Jun 14.
    1. Lin J, Wang MX, Wei A, Zhu W, Murrell GA. The cell specific temporal expression of nitric oxide synthase isoforms during achilles tendon healing. Inflamm Res. 2001;50:515–22. doi: 10.1007/PL00000228.
    1. Berrazueta JR, Losada A, Poveda J, et al. Successful treatment of shoulder pain syndrome due to supraspinatus tendinitis with transdermal nitroglycerin. A double blind study. Pain. 1996;66:63–7. doi: 10.1016/0304-3959(96)03021-7.
    1. Paoloni JA, Appleyard RC, Nelson J, Murrel GA. Topical nitric oxide application in the treatment of chronic extensor tendinosis at the elbow: a randomized, double-blinded, placebo-controlled clinical trial. Am J Sports Med. 2003;31:915–20.
    1. Paoloni JA, Appleyard RC, Nelson J, Murrel GA. Topical glyceryl trinitrate treatment of chronic noninsertional achilles tendinopathy. A randomized, double-blind, placebo-controlled trial. J Bone Joint Surg Am. 2004;86-A:916–22.
    1. Paoloni JA, Appleyard RC, Nelson J, Murrel GA. Topical glyceryl trinitrate application in the treatment of chronic supraspinatus tendinopathy: a randomized, double-blinded, placebo-controlled clinical trial. Am J Sports Med. 2005;33:806–13. doi: 10.1177/0363546504270998. Epub 2005 Apr 12.
    1. Paoloni JA, Murrel GA. Three-year followup study of topical glyceryl trinitrate treatment of chronic noninsertional Achilles tendinopathy. Foot Ankle Int. 2007;28:1064–8. doi: 10.3113/FAI.2007.1064.
    1. Basford JR, Malanga GA, Krause DA, et al. A randomized controlled evaluation of low-intensity laser therapy: Plantar fasciitis. Arch Phys Med Rehabil. 1998;79:249–254. doi: 10.1016/S0003-9993(98)90002-8.
    1. Stergioulas A, Stergioula M, Aarskog R, Lopes-Martins RA, Bjordal JM. Effects of low-level laser therapy and eccentric exercises in the treatment of recreational athletes with chronic Achilles tendinopathy. Am J Sports Med. 2008 Feb 13. doi: 10.1177/0363546507312165.
    1. Bjordal JM, Lopes-Martins RA, Iversen VV. A randomised, placebo controlled trial of low level laser therapy for activated Achilles tendinitis with microdialysis measurement of peritendinous prostaglandin E2 concentrations. Br J Sports Med. 2006;40:76–80. doi: 10.1136/bjsm.2005.020842.
    1. Basford JR. The clinical and experimental status of low-energy laser therapy. Crit Rev Phys Rehabil Med. 1989;1:1–9.
    1. Herman JH, Khosla RC. In vitro effects of Nd: YAG laser radiation on cartilage metabolism. J Rheumatol. 1988;15:1818–1826.
    1. Brown AW, Weber DC. Physical agent modalities. In: Braddom RL, editor. Physical medicine and rehabilitation. London: W.B. Saunders Co; 2000. pp. 440–458.
    1. Ohberg L, Alfredson H. Ultrasound guided sclerosis of neovessels in painful chronic Achilles tendinosis: pilot study of a new treatment. Br J Sports Med. 2002;36:173–5. doi: 10.1136/bjsm.36.3.173.
    1. Ohberg L, Alfredson H. Sclerosing therapy in chronic Achilles tendon insertional pain-results of a pilot study. Knee Surg Sports Traumatol Arthrosc. 2003;11:339–43. doi: 10.1007/s00167-003-0402-7.
    1. Hoksrud A, Ohberg L, Alfredson H, Bahr R. Ultrasound-Guided Sclerosis of Neovessels in Painful Chronic Patellar Tendinopathy: A Randomized Controlled Trial. Am J Sports Med. 2006;34:1738–46. doi: 10.1177/0363546506289168.
    1. Lind B, Ohberg L, Alfredson H. Sclerosing polidocanol injections in mid-portion Achilles tendinosis: remaining good clinical results and decreased tendon thickness at 2-year follow-up. Knee Surg Sports Traumatol Arthrosc. 2006;14:1327–32. doi: 10.1007/s00167-006-0161-3. Epub 2006 Sep 12.
    1. Maxwell NJ, Ryan MB, Taunton JE, Gillies JH, Wong AD. Sonographically guided intratendinous injection of hyperosmolar dextrose to treat chronic tendinosis of the Achilles tendon: a pilot study. AJR Am J Roentgenol. 2007;189:W215–20. doi: 10.2214/AJR.06.1158.
    1. Knobloch K, Spies M, Vogt PM. Adverse effects of intratendinous injection. AJR Am J Roentgenol. 2008;190:W316. doi: 10.2214/AJR.07.3380.
    1. Zeisig E, Fahlstrom M, Ohberg L, Alfredson H. Pain relief after intratendinous injections in patients with tennis elbow: results of a randomised study. Br J Sports Med. 2008;42:267–71. doi: 10.1136/bjsm.2007.042762.
    1. Knobloch K, Hoffmann N, Schiffke B, Redeker B, Vogt PM. The injected agent with color Doppler – does it matter in tennis elbow. Br J Sports Med. 2008 Apr 4 [eLetter]

Source: PubMed

Sponzoři a spolupracovníci

Zdravotní podmínky

Drogové intervence

3
Předplatit