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Non-invasive low frequency vibration as a potential emergency adjunctive treatment for heart attack and stroke. An in vitro flow model

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Abstract

Background

Myocardial infarction and stroke (arterial thrombosis) comprise the leading killers and sources of disability in the developed world, and incomplete thrombolysis along with high bleeding rates (plus late presentations to cathlabs) have prompted an intensive search for alternative or adjunctive emergency therapies. Transcutaneous ultrasound has been studied in remediation of thrombosis, but has been problematic due to poor penetration, risk of arterial damage, plus the apparent need for a highly skilled approach. Surprisingly there has been no reported studies on the much simpler application of transcutaneous low frequency vibration (well known for its superior penetration and flow enhancing characteristics) to assist arterial thrombolysis. The aim of our experiment therefore was to test the hypothesis whether vibration (i.e. ∼100 Hz, 0.5 mm), when applied across an attenuating barrier, would assist recanulization of a thrombosed flow system held at arterial like pressure.

Methods

A teddy bear with a 2 cm slab of New York Steak placed upon its chest surface was used as a test subject with an in-dwelling catheter (∼4.0 mm lumen) cannulated through the bear’s thorax. In a series of test runs (n = 30), a 2 h old (or older) blood clot was injected into the catheter such as to occlude it at a stenosis site (∼90% luminal narrowing) created by a clamp placed along the catheter within the teddy’s chest region. A pressurized heparinized IV system was in all cases connected to the catheter such as to yield an “arterial like” lumen pressure proximal the obstruction. For each test run, after a twenty minute observation period to confirm stability of the occlusion, test groups where randomized to receive vibration to the slab of steak upon the teddy’s “chest wall” (generally overlying the site of the thrombotic obstruction), or no vibration for an evaluation period of up to 45 min.

Results

Catheter reflow occurred rapidly (median reflow-time 90 s) in the vibration groups within the evaluation period (i.e. 15/17), while the system remained otherwise blocked in the control groups receiving no vibration (i.e. 0/13). The difference in flow system patency rate for the vibration groups vs. the control groups was statistically significant (P = 0.0000009).

Conclusions

The frequent and generally rapid re-establishment of flow in vibration groups compared to the complete absence of reflow in control groups confirms the hypothesis that vibration applied across a physical barrier assists clearance of a blood clot in a stenosed flow system under systemic levels of pressure.

Abbreviated abstract

We studied the incidence of clearance of a blood clot within a stenosed, heparanized catheter system held at arterial like pressure that was treated with externally delivered low frequency vibration (applied proximate the thrombotic occlusion across an attenuating medium––a 2 cm thick slab of New York Steak––at ∼100 Hz, 0.5 mm), versus no vibration. Reflow in test runs incorporating vibration occurred faster, and resulted in significantly greater recanulization rates in the catheter system versus test runs without vibration (P = 0.0000009). Non-invasive vibration holds potential as an adjunct to pharmacologic therapy in treatment of acute arterial thrombosis. Further study of this technique appears warranted in live animal models.

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References

  1. Lincoff AM, Topol EJ (1993) Illusion of reperfusion. Does anyone achieve optimal reperfusion during acute myocardial infarction? Circulation 88:1361–1374

    PubMed  CAS  Google Scholar 

  2. The National Institute of Neurological Disorders and Stroke t-PA Stroke Study Group (1995) Tissue plasminogen activator for acute ischemic stroke. N Engl J Med 333:1581–1587

    Article  Google Scholar 

  3. Stone GW, Cox D, Garcia E et al (2001) Normal flow (TIMI-3) before mechanical reperfusion therapy is an independent determinant of survival in acute myocardial infarction. Circulation 104:636–641

    Article  PubMed  CAS  Google Scholar 

  4. Cannon CP (2001) Importance of TIMI 3 flow. Circulation (Editorial) 104:624–626

    CAS  Google Scholar 

  5. Ross AM, Coyne KS, Moreyra E et al (1998) Extended mortality benefit of early postinfarction reperfusion. GUSTO-I Angiopgraphic Investigators. Global Utilization of streptokinase and tissue plasminogen activator for occluded coronary arteries trial. Circulation 97:1549–1556

    PubMed  CAS  Google Scholar 

  6. Anderson JL, Karagounis LA, Becker LC, Sorensen SG, Menlove RL (1993) TIMI perfusion grade 3 but not grade 2 results in improved outcome after thrombolytisis for myocardial infarction. Ventriculographic, enzymatic, and electrocardiographic evidence from the TEAM 3 Study. Circulation 87:1829–1839

    PubMed  CAS  Google Scholar 

  7. Llevadot J, Giugliano RP, Antman EM (2001) Bolus fibrionolytic therapy in acute myocardial infarction. J Am Med Assoc 286(4):442–449

    Article  CAS  Google Scholar 

  8. Molina CA, Ribo M, Rubiera M et al (2006) Microbubble administration accelerates clot lysis during continuous 2-MHz ultrasound monitoring in stroke patients treated with intravenous tissue plasminogen activator. Stroke 37(2):425–429

    Article  PubMed  CAS  Google Scholar 

  9. Saver JL (2006) Time is brain-quantified. Stroke 37(1):263–266

    Article  PubMed  Google Scholar 

  10. Jacobs AK. Speedy angioplasty urged for more heart attack patients. American Heart Association Consensus Statement. 2006; Report, http://www.americanheart.org

  11. Woo MA (1992) Clinical management of the patient with an acute myocardial infarction. Nurs Clin North Am 27(1):189–203

    PubMed  CAS  Google Scholar 

  12. NG KY, Liu Y (2002) Therapeutic ultrasound: its application in drug delivery. Med Res Rev 22(2):204–223

    Article  PubMed  CAS  Google Scholar 

  13. Alexandrov AV, Molina CA, Grotta JC (CLOTBUST Investigators) et al (2004) Ultrasound-enhanced systemic thrombolysis for acute ischemic stroke. N Engl J Med 351(21):2170–2178

    Article  PubMed  CAS  Google Scholar 

  14. Cohen MG, Tuero E, Bluguermann J et al (2003) Transcutaneous ultrasound-facilitated coronary thrombolysis during acute myocardial infarction. Am J Cardiol 92(4):454–457

    Article  PubMed  Google Scholar 

  15. Daffertshofer M, Gass A, Ringleb P et al (2005) Transcranial low-frequency ultrasound-mediated thrombolysis in brain ischemia: increased risk of hemorrhage with combined ultrasound and tissue plasminogen activator: results of a phase II clinical trial. Stroke 36(7):1441–1446

    Article  PubMed  Google Scholar 

  16. Wells PM (1975) Review. Absorption and dispersion of ultrasound in biological tissue. Ultrasound Med Biol 1:369–376

    Article  PubMed  CAS  Google Scholar 

  17. Pfaffenberger S, Devcic-Kuhar B, Kollmann C et al (2005) Can a commercial diagnostic ultrasound device accelerate thrombolysis? An in vitro skull model. Stroke 36(1):124–128

    Article  PubMed  Google Scholar 

  18. Frizzel LA, Miller DL, Nyborg WL (1986) Ultrasonically induced intravascular streaming and thrombus formation adjacent to a micropipette. Ultrasound Med Biol 12(3):217–221

    Article  Google Scholar 

  19. Kornowski R, Meltzer R (1994) Does external ultrasound accelerate thrombolysis? Results from a rabbit model. Circulation 89:339–344

    PubMed  CAS  Google Scholar 

  20. Mukherjee D, Wong J, Griffin B (2000) Ten fold augmentation of endothelial uptake of vascular endothelial growth factor with ultrasound after systemic administration. J Am Coll Cordiol 35(6):1678–1686

    Article  CAS  Google Scholar 

  21. Riggs PN, Francis CW, Bartos SR, Penney DP (1997) Ultrasound enhancement of rabbit femoral artery thrombolysis. Cardiovasc Surg 5(2):201–207

    Article  PubMed  CAS  Google Scholar 

  22. Nishioka T, Luo H, Fishbein MC et al (1997) Dissolution of thrombotic arterial occlusion by high intensity, low frequency ultrasound and dodecafluoropentane emulsion: an in vitro and in vivo study. J Am Coll Cordiol 30(2):561–568

    Article  CAS  Google Scholar 

  23. Luo H, Nishioka T, Fishbein MC et al (1996) Transcutaneous ultrasound augments lysis of arterial thrombi in vivo. Circulation 94:775–778

    PubMed  CAS  Google Scholar 

  24. Kerr CL, Gregory DW, Chan KK, Wattmough DJ, Wheatly DN (1989) Ultrasound-induced damage of veins in pig ears, as revealed by scanning electron microscopy. Ultrasound Med Biol 15:45–52

    Article  PubMed  CAS  Google Scholar 

  25. Koiwa Y, Honda H, Takagi T, Kikuchi J, Hoshi N, Takishima T (1997) Modification of human left ventricular relaxation by small-amplitude, phase–controlled mechanical vibration on the chest wall. Circulation 95:156–162

    PubMed  CAS  Google Scholar 

  26. Thomas J, Cook DJ, Brooks D (1995) Chest physical therapy management of patients with cystic fibrosis: a meta analysis. Am J Respir Crit Care Med 151:846–850

    PubMed  CAS  Google Scholar 

  27. Koiwa Y, Hashiguchi R, Ohyama T et al (1986) Measurement of instantaneous viscoelastic properties by impedance-frequency curve of the ventricle. Am J Physiol 250:H672–H684

    PubMed  CAS  Google Scholar 

  28. Hashiguchi R, Koiwa Y, Ohyama T et al (1988) Dependence of instantaneous transfer function on regional ischemic myocardial volume. Circ Res 63:1003–1011

    PubMed  CAS  Google Scholar 

  29. Smith D, Ishimitsu T, Craige E (1984) Mechanical vibration transmission characteristics of the left ventricle. implication with regard to auscultation and phonocardiography. J Am Coll Cordiol 4(3):517–521

    Article  CAS  Google Scholar 

  30. Farber JJ, Purvis JH (1963) Conduction of cardiovascular sound along arteries. Circ Res 12:308–316

    PubMed  CAS  Google Scholar 

  31. Wobser E, Stumpff U (1978) Intragastral disintegration of blood coagula by mechanical vibration. Endoscopy 10:15–19

    PubMed  CAS  Google Scholar 

  32. Dubrul WR, Evans MA (2001) Motion catheter. US Patent 6,287,271

  33. Folts J (1991) An in vivo model of experimental arterial stenosis, intimal damage, and periodic thrombosis. Circulation 83(IV):IV-3–IV-14

    CAS  Google Scholar 

  34. Folts J (2000) Contemporary cardiology vascular disease and injury preclinical research (Chap. 11). Humana Press Inc., Totowa, NJ, pp 127–145

  35. Antman EM, Anbe DT, Armstrong PW et al (2004) ACC/AHA guidelines for the management of patient’s with STEMI: executive summary. J Am Coll Cardiol 44(3):671–719

    Article  PubMed  Google Scholar 

  36. Lindblad LE, Lorenz RR, Shepherd JT, Vanhoutte PM (1986) Effect of vibration on canine cutaneous artery. Heart Circ Physiol 19:H519–H523

    Google Scholar 

  37. Ljung B, Silvertsson R (1975) Vibration-induced inhibition of vascular smooth muscle contraction. Blood Vessels 12:38–52

    PubMed  CAS  Google Scholar 

  38. Hudlicka O, Wright A (1978) The effect of vibration on blood flow in skeletal muscle in rabbit. Clin Sci Mol Med 55:471–476

    Google Scholar 

  39. Koiwa Y, Honda H, Hoshi N, Naya T, Kamada E. The effect of diastolic vibration on the coronary flow rate in the canine heart with ischemia. J Cardiovasc Diagn Procedures 1994; Abstract (FRI – POS 05)12:110

  40. Naya T, Koiwa Y, Honda H et al Diastolic vibration from the precordium increases coronary blood flow in humans. J Cardiovasc Diagn Procedures 1994; Abstract (FRI – POS07) 12:110

    Google Scholar 

  41. Bozeman WP, Kleiner DM, Ferguson KL (2006) Empiric tenecteplase is associated with increased return of spontaneous circulation and short term survival in cardiac arrest patients unresponsive to standard interventions. Resuscitation 69(3):399–406

    Article  PubMed  Google Scholar 

  42. Takashima H, Tsuruta H, Higashi T, Watanabe M, Isomoto A, Tyuma I. Effects of mechanical force on blood fibrinolytic activity. Thromb Haemost 1987; Abstract 58:550

    Google Scholar 

  43. Tarnay TJ, Rohr PR, Davidson AG, Stevenson MM, Byars EF, Hopkins GR (1980) Pneumatic calf compression, fibrinolysis, and the prevention of deep venous thrombosis. Surgery 88(4):489–496

    PubMed  CAS  Google Scholar 

  44. Adams JA, Bassuk J, Dongmei W, Grana M, Kurlansky P, Sackner M (2005) Periodic acceleration: effects on vasoactive, fibrinolytic, and coagulation factors. J Appl Physiol 98:1083–1090

    Article  PubMed  CAS  Google Scholar 

  45. Takagi T, Koiwa Y, Kikuchi J et al (1992) Diastolic vibration improves systolic function in cases of incomplete relaxation. Circulation 86:1955–1964

    PubMed  CAS  Google Scholar 

  46. Koiwa Y, Takagi T, Kikuchi H, Honda H, Hoshi N, Takishima T (1989) The improvement of systolic function of depressed left ventricle by external vibration at diastole. Tohoku J Exp Med 159:169–170

    Article  PubMed  CAS  Google Scholar 

  47. Silver MC, Baroldi G, Marian F (1980) The relationship between acute occlusive coronary thrombi and myocardial infarction studied in 100 consecutive patients. Circulation 61(2):219–227

    PubMed  CAS  Google Scholar 

  48. Hackett D, Davies G, Chierchia S, Maseri A (1987) Intermittent coronary occlusion in acute myocardial infarction. N Engl J Med 317(17):1055–1059

    Article  PubMed  CAS  Google Scholar 

  49. Dalen JE, Ockene IS, Alpert JS (1982) Coronary spasm, coronary thrombosis, and myocardial infarction: a hypothesis concerning the pathophysiology of acute myocardial infarction. Am Heart J 104(5):1119–1124

    Article  PubMed  CAS  Google Scholar 

  50. Oliva PB, Breckinridge JC (1977) Arteriographic evidence of coronary arterial spasm in acute myocardial infarction. Circulation 56(3):367–374

    Google Scholar 

  51. Maseri A, L’Abbate A, Baroldi G et al (1978) Coronary vasospasm as a possible cause of myocardial infarction. N Engl J Med 299(23):1271–1277

    Article  PubMed  CAS  Google Scholar 

  52. Marder VJ, Chute DJ, Starkman S et al (2006) Analysis of thrombi retrieved from cerebral arteries of patients with acute ischemic stroke. Stroke 37(8):2086–2093

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

The author gratefully thanks Dr. C. Michael Gibson for his peer review and Dr. Dante Manyari for his advice in the drafting of this manuscript. Also, many thanks to the Royal Columbian (Cardiac Cath Lab) and Surrey Memorial Hospital (Laboratory) for the loan and donation of select equipment and supplies and assistance in blood collection which made this study possible. This study was otherwise sponsored by Ahof Biophysical Systems Inc.

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Correspondence to Fesseha G. Yohannes.

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Yohannes, F.G., Hoffmann, A.K. Non-invasive low frequency vibration as a potential emergency adjunctive treatment for heart attack and stroke. An in vitro flow model. J Thromb Thrombolysis 25, 251–258 (2008). https://doi.org/10.1007/s11239-007-0054-4

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  • DOI: https://doi.org/10.1007/s11239-007-0054-4

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